Materiały źródłowe

• #1 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multiomics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. […] Autism spectrum disorder result from a combination of genetic and environmental factors, with heterogeneity being a predominant characteristic. Despite this diversity, there exist convergent disease mechanisms and shared pathological features that provide a basis for diagnosis, treatment, and intervention, particularly in the context of stratification or subcategories. Besides, there remains optimism regarding the identification of specific mechanisms and the development of targeted diagnostic and therapeutic approaches.

• #2 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The etiology of ASD is extremely complex. Twin studies suggest that genes play a key role in the pathogenesis of ASD, and its heritability estimates range from 64% to 91%. In families with children with ASD, the average rate of ASD recurrence is estimated to be 15%25% for male newborns and 5%15% for female newborns. Besides, environmental factors are also implicated in the development of ASD, including prenatal/perinatal, microbialgutbrain axis, and others. Prenatal/perinatal causes included maternal age 35 years, maternal characteristics of metabolic syndrome, use of antidepressant valproic acid (VPA) medications, and the effects of infection and inflammation. Environmental factors can directly influence specific susceptibility genes, prompting epigenetic modifications such as DNA methylation and histone changes (phosphorylation and acetylation), which increase the risk of developing ASD. ASD arises from a complex interplay of genetic and environmental factors, leading to changes in brain structure and function that manifest as behavioral abnormalities.

• #3 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The etiology of ASD is extremely complex. Twin studies suggest that genes play a key role in the pathogenesis of ASD, and its heritability estimates range from 64% to 91%. In families with children with ASD, the average rate of ASD recurrence is estimated to be 15%25% for male newborns and 5%15% for female newborns. Besides, environmental factors are also implicated in the development of ASD, including prenatal/perinatal, microbialgutbrain axis, and others. Prenatal/perinatal causes included maternal age 35 years, maternal characteristics of metabolic syndrome, use of antidepressant valproic acid (VPA) medications, and the effects of infection and inflammation. Environmental factors can directly influence specific susceptibility genes, prompting epigenetic modifications such as DNA methylation and histone changes (phosphorylation and acetylation), which increase the risk of developing ASD. ASD arises from a complex interplay of genetic and environmental factors, leading to changes in brain structure and function that manifest as behavioral abnormalities.

• #4 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multiomics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. […] Autism spectrum disorder result from a combination of genetic and environmental factors, with heterogeneity being a predominant characteristic. Despite this diversity, there exist convergent disease mechanisms and shared pathological features that provide a basis for diagnosis, treatment, and intervention, particularly in the context of stratification or subcategories. Besides, there remains optimism regarding the identification of specific mechanisms and the development of targeted diagnostic and therapeutic approaches.

• #5 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. […] Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. […] These include SHANK, NLGN, NRXN, FMR1, and MECP2 as well as other potentially novel genes such as CHD8, CHD2, and SYNGAP1 that could be core elements in ASD pathogenesis. […] Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD. […] The etiology of ASD is still unclear, but multiple genetic and environmental factors are thought to be involved.

• #6 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  So far, more than 1000 genes or genomic loci have been associated with ASD. […] Genetic abnormalities in ASD include chromatin remodeling disorders, DNA mutations, mRNA transcription and translation disorders, altered protein modifications, and altered epigenetic modifications. […] These can lead to disorders of synaptic structure and functions, alterations in ion channels, and dysfunctional signaling pathways. […] Recent studies have found that genes such as FMR1, NRXN, NLGN, SHANK, MECP2, CDH8, GRIN, and SYNGAP1 are associated with ASD, while also playing major roles in synaptogenesis, synaptic maturation, transmission, and plasticity. […] Together, the results to date indicate that synaptic disorders may be the most important contributor to the pathogenesis of ASD. […] The formation and maturation of synapses is crucial for the development of brain neural circuits, and synaptic dysfunction is a potential pathogenic factor in developmental disorders of the brain.

• #7 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Here, we reviewed the underlying mechanisms with the association of ASD risk genes, omics studies, ASD occurrence in different genetic backgrounds, and its common mechanisms between ASD and its comorbidities. We also summarized the mechanisms associated with important physiological and metabolic abnormalities, as well as gut microbiota. […] Single gene mutations merely account for 1%2% of autism cases and they act through distinct molecular pathways. We gathered the ASD risk genes from SFARI database and categorized them into three groups based on risk level. The Gene Ontology (GO) analysis was conducted on three groups, respectively. In the first set, most of risk genes were enriched in histone modification, cognition, as well as regulation of transporter activity pathway. Regulation of neurological system process, synapse organization, and social behavior pathways were placed in a prominent position within pathway network. These results implicated that impairment of cognition is the most obvious character. Individuals with autism spectrum conditions or rare mutation related to ASD have profound impairments in the interpersonal social domain. In the second set, a majority of the risk genes exhibited enrichment in modulation of synaptic transmission, synapse organization, and learning or memory. Additionally, some pathways involved human traits and actions were found, including learning or memory, social behavior, mating, circadian rhythm, sleep, and locomotory behavior. The change of these human action may be potential indication for ASD. In the third set, many risk genes were enriched in cellular response to peptide, regulation of cell growth, and modulation of synaptic transmission.

• #8 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  So far, more than 1000 genes or genomic loci have been associated with ASD. […] Genetic abnormalities in ASD include chromatin remodeling disorders, DNA mutations, mRNA transcription and translation disorders, altered protein modifications, and altered epigenetic modifications. […] These can lead to disorders of synaptic structure and functions, alterations in ion channels, and dysfunctional signaling pathways. […] Recent studies have found that genes such as FMR1, NRXN, NLGN, SHANK, MECP2, CDH8, GRIN, and SYNGAP1 are associated with ASD, while also playing major roles in synaptogenesis, synaptic maturation, transmission, and plasticity. […] Together, the results to date indicate that synaptic disorders may be the most important contributor to the pathogenesis of ASD. […] The formation and maturation of synapses is crucial for the development of brain neural circuits, and synaptic dysfunction is a potential pathogenic factor in developmental disorders of the brain.

• #9 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Here, we reviewed the underlying mechanisms with the association of ASD risk genes, omics studies, ASD occurrence in different genetic backgrounds, and its common mechanisms between ASD and its comorbidities. We also summarized the mechanisms associated with important physiological and metabolic abnormalities, as well as gut microbiota. […] Single gene mutations merely account for 1%2% of autism cases and they act through distinct molecular pathways. We gathered the ASD risk genes from SFARI database and categorized them into three groups based on risk level. The Gene Ontology (GO) analysis was conducted on three groups, respectively. In the first set, most of risk genes were enriched in histone modification, cognition, as well as regulation of transporter activity pathway. Regulation of neurological system process, synapse organization, and social behavior pathways were placed in a prominent position within pathway network. These results implicated that impairment of cognition is the most obvious character. Individuals with autism spectrum conditions or rare mutation related to ASD have profound impairments in the interpersonal social domain. In the second set, a majority of the risk genes exhibited enrichment in modulation of synaptic transmission, synapse organization, and learning or memory. Additionally, some pathways involved human traits and actions were found, including learning or memory, social behavior, mating, circadian rhythm, sleep, and locomotory behavior. The change of these human action may be potential indication for ASD. In the third set, many risk genes were enriched in cellular response to peptide, regulation of cell growth, and modulation of synaptic transmission.

• #10 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Here, we reviewed the underlying mechanisms with the association of ASD risk genes, omics studies, ASD occurrence in different genetic backgrounds, and its common mechanisms between ASD and its comorbidities. We also summarized the mechanisms associated with important physiological and metabolic abnormalities, as well as gut microbiota. […] Single gene mutations merely account for 1%2% of autism cases and they act through distinct molecular pathways. We gathered the ASD risk genes from SFARI database and categorized them into three groups based on risk level. The Gene Ontology (GO) analysis was conducted on three groups, respectively. In the first set, most of risk genes were enriched in histone modification, cognition, as well as regulation of transporter activity pathway. Regulation of neurological system process, synapse organization, and social behavior pathways were placed in a prominent position within pathway network. These results implicated that impairment of cognition is the most obvious character. Individuals with autism spectrum conditions or rare mutation related to ASD have profound impairments in the interpersonal social domain. In the second set, a majority of the risk genes exhibited enrichment in modulation of synaptic transmission, synapse organization, and learning or memory. Additionally, some pathways involved human traits and actions were found, including learning or memory, social behavior, mating, circadian rhythm, sleep, and locomotory behavior. The change of these human action may be potential indication for ASD. In the third set, many risk genes were enriched in cellular response to peptide, regulation of cell growth, and modulation of synaptic transmission.

• #11 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. […] Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. […] These include SHANK, NLGN, NRXN, FMR1, and MECP2 as well as other potentially novel genes such as CHD8, CHD2, and SYNGAP1 that could be core elements in ASD pathogenesis. […] Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD. […] The etiology of ASD is still unclear, but multiple genetic and environmental factors are thought to be involved.

• #12 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  So far, more than 1000 genes or genomic loci have been associated with ASD. […] Genetic abnormalities in ASD include chromatin remodeling disorders, DNA mutations, mRNA transcription and translation disorders, altered protein modifications, and altered epigenetic modifications. […] These can lead to disorders of synaptic structure and functions, alterations in ion channels, and dysfunctional signaling pathways. […] Recent studies have found that genes such as FMR1, NRXN, NLGN, SHANK, MECP2, CDH8, GRIN, and SYNGAP1 are associated with ASD, while also playing major roles in synaptogenesis, synaptic maturation, transmission, and plasticity. […] Together, the results to date indicate that synaptic disorders may be the most important contributor to the pathogenesis of ASD. […] The formation and maturation of synapses is crucial for the development of brain neural circuits, and synaptic dysfunction is a potential pathogenic factor in developmental disorders of the brain.

• #13 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  The complexity of ASD genetic architecture has been inspiring a sustained effort towards the identification of convergent molecular pathways that can group genetic mutations into categories sharing an analogous impact on neurodevelopment, thus explaining the similarity of the observed phenotypes. […] The evidence of epigenetic and transcriptional dynamics as one of the functional domains more consistently linked to ASD is related especially to genes coding for DNA and RNA binding proteins. […] A paradigmatic example of an RNA-binding protein related to mRNA dynamics is FMRP (Fragile X mental retardation protein). […] Even more interestingly, recent data indicates that this convergence at the functional level could hold true also when examining different NDDs and psychiatric disorders.

• #14 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. […] Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. […] These include SHANK, NLGN, NRXN, FMR1, and MECP2 as well as other potentially novel genes such as CHD8, CHD2, and SYNGAP1 that could be core elements in ASD pathogenesis. […] Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD. […] The etiology of ASD is still unclear, but multiple genetic and environmental factors are thought to be involved.

• #15 Molecular pathogenesis of autism spectrum disorder using human disease models – Brain/MINDS 2.0

  https://brainminds.jp/en/research/1944

  Molecular pathogenesis of autism spectrum disorder using human disease models […] Recently, the chromatin remodeling factor CHD8 has been identified as the most promising candidate gene for ASD. […] We have generated mice that replicate the CHD8 mutation observed in individuals with ASD and demonstrated that these mice exhibit ASD-like symptoms due to delayed neurogenesis and abnormalities in neural circuits. […] In this study, we aim to identify cell populations involved in the development of ASD during neurogenesis and to characterize the neural circuits constructed by these cells, with the ultimate goal of developing evidence-based treatments.

• #16 A novel mechanism involved in the pathophysiology of autism spectrum disorder – Promote the establishment of therapeutic strategies and the development of new drugs for autism spectrum disorder – | Japan Agency for Medical Research and Development

  https://www.amed.go.jp/en/news/release_20201012.html

  The causal relationship between synaptic dysfunction and impaired social interaction was revealed and the brain region responsible for impaired social interaction was successfully identified in a mouse experiment with the CNTNAP2 and AHI1 genes, i.e., candidate genes for autism spectrum disorder (ASD). […] Specifically, the synaptic dysfunction of pyramidal cells in the prefrontal cortex may cause ASD symptoms. […] The results of this research project should promote the establishment of new therapeutic strategies and the development of new drugs for ASD.

• #17 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. […] Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. […] Here, we will focus on ASD as a paradigmatic example of NDD whose manifestation is the outcome of a complex interaction of predisposition factors and genetic or environmental lesions. We will elucidate how both genetic alterations and toxic insults can be at the root of the pathogenetic events that trigger NDDs, highlighting the growing body of evidence pointing towards an interplay between the individual genetic make-up and the environmental exposures occurring in early life, and their convergence towards key molecular pathways.

• #18 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The heterogeneity of ASD impedes both pinpointing underlying mechanisms and tailoring effective therapies. Interestingly, the previous studies have shown that the function of ASDassociated genes converges with the affected cell type and that the affected brain has a characteristic molecular pathology. ASDspecific molecular changes are mainly concentrated in central nervous system (CNS). Besides, individuals with ASD have different comorbidities, but all share the same social communication deficits and repetitive stereotyped behavioral phenotypes, implying a common underlying biological mechanism among them. The heterogeneity of ASD does not preclude the possibility of finding common features or mechanisms that could lead to breakthroughs in the pathogenesis, diagnosis, and treatment of ASD. Efforts have been made to identify biomarkers, pathological mechanisms, and drug targets, and to explore the possibility of defining ASD subgroups by biological features.

• #19 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The main signaling pathways involved in synaptic dysfunction include phosphatidylinositol 3kinase/Protein kinase B/Mammmalian target of rapamycin (PI3K/Akt/mTOR) signal and abnormal autophagy, extracellular signalregulated kinase/mitogenactivated protein kinase (ERK/MAPK) signal, Janus kinase and microtubule interacting protein 1 (JAKMIP1) pathway, and calcium signaling. Among them, dysregulation of the PI3K/Akt/mTOR pathway was considered as a point of convergence ASD. mTORC1 severed as a key role to tightly coordinates synaptic signaling pathways downstream of glutamate and neurotrophic receptors. […] Accumulating evidence suggested ERK/MAPK signaling as a downstream mediator of divergent genetic mutations linked to certain forms of autism. It also could be a converge on mTOR signaling pathway. A global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 were found in Fmr1KO cell lines.

• #20 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The main signaling pathways involved in synaptic dysfunction include phosphatidylinositol 3kinase/Protein kinase B/Mammmalian target of rapamycin (PI3K/Akt/mTOR) signal and abnormal autophagy, extracellular signalregulated kinase/mitogenactivated protein kinase (ERK/MAPK) signal, Janus kinase and microtubule interacting protein 1 (JAKMIP1) pathway, and calcium signaling. Among them, dysregulation of the PI3K/Akt/mTOR pathway was considered as a point of convergence ASD. mTORC1 severed as a key role to tightly coordinates synaptic signaling pathways downstream of glutamate and neurotrophic receptors. […] Accumulating evidence suggested ERK/MAPK signaling as a downstream mediator of divergent genetic mutations linked to certain forms of autism. It also could be a converge on mTOR signaling pathway. A global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 were found in Fmr1KO cell lines.

• #21 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The main signaling pathways involved in synaptic dysfunction include phosphatidylinositol 3kinase/Protein kinase B/Mammmalian target of rapamycin (PI3K/Akt/mTOR) signal and abnormal autophagy, extracellular signalregulated kinase/mitogenactivated protein kinase (ERK/MAPK) signal, Janus kinase and microtubule interacting protein 1 (JAKMIP1) pathway, and calcium signaling. Among them, dysregulation of the PI3K/Akt/mTOR pathway was considered as a point of convergence ASD. mTORC1 severed as a key role to tightly coordinates synaptic signaling pathways downstream of glutamate and neurotrophic receptors. […] Accumulating evidence suggested ERK/MAPK signaling as a downstream mediator of divergent genetic mutations linked to certain forms of autism. It also could be a converge on mTOR signaling pathway. A global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 were found in Fmr1KO cell lines.

• #22 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The alteration of JAKMIP1 could be found in individuals with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. […] Calcium signaling has a prominent effect on pathogenesis of ASD. An action of calcium ion plays an essential role for neurodevelopment. ERK signaling has also been found to be greatly linked to calcium channels to cause abnormal synaptic functions, chromatin remodeling, and ion channel activity. […] Accumulating evidence supported a hypothesis that the imbalance between excitation and inhibition (E/I) caused by changes in the availability of glutamate and/or GABA signal transmission contribute to pathological synaptic transmission and neural circuits in ASD. […] The PSD of synapses is a wide range of scaffolding proteins, receptors, and signaling molecules that acts as a switchboard of neurotransmitter molecular and have strong association to ASD. Glutamate receptor levels could be regulated by endocytosis of PSD scaffolding proteins. In general, E/I balance required the integrity of PSD to transmit signal between neuros.

• #23 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The alteration of JAKMIP1 could be found in individuals with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. […] Calcium signaling has a prominent effect on pathogenesis of ASD. An action of calcium ion plays an essential role for neurodevelopment. ERK signaling has also been found to be greatly linked to calcium channels to cause abnormal synaptic functions, chromatin remodeling, and ion channel activity. […] Accumulating evidence supported a hypothesis that the imbalance between excitation and inhibition (E/I) caused by changes in the availability of glutamate and/or GABA signal transmission contribute to pathological synaptic transmission and neural circuits in ASD. […] The PSD of synapses is a wide range of scaffolding proteins, receptors, and signaling molecules that acts as a switchboard of neurotransmitter molecular and have strong association to ASD. Glutamate receptor levels could be regulated by endocytosis of PSD scaffolding proteins. In general, E/I balance required the integrity of PSD to transmit signal between neuros.

• #24 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The alteration of JAKMIP1 could be found in individuals with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. […] Calcium signaling has a prominent effect on pathogenesis of ASD. An action of calcium ion plays an essential role for neurodevelopment. ERK signaling has also been found to be greatly linked to calcium channels to cause abnormal synaptic functions, chromatin remodeling, and ion channel activity. […] Accumulating evidence supported a hypothesis that the imbalance between excitation and inhibition (E/I) caused by changes in the availability of glutamate and/or GABA signal transmission contribute to pathological synaptic transmission and neural circuits in ASD. […] The PSD of synapses is a wide range of scaffolding proteins, receptors, and signaling molecules that acts as a switchboard of neurotransmitter molecular and have strong association to ASD. Glutamate receptor levels could be regulated by endocytosis of PSD scaffolding proteins. In general, E/I balance required the integrity of PSD to transmit signal between neuros.

• #25 Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3733014/

  However, how these mutations lead to ASD phenotypes is poorly understood. In addition, many ASD-related genes are also associated with other neuropsychiatric disorders. […] Defects in synaptic proteins would lead to defective transmissions at excitatory and inhibitory synapses, disrupting the E-I balance in postsynaptic neurons, a key mechanism implicated in ASD. […] The idea that Shanks are involved in the etiology of ASD firstly emerged from Phelan-McDermid syndrome (PMS) or 22q13 deletion syndrome, a neurodevelopmental disorder caused by a microdeletion on chromosome 22. The association between SHANK and ASD became evident by identifying numerous mutations including de novo frameshift, truncating, and missense mutations on SHANK3 locus in autistic individuals.

• #26 Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances

  https://www.imrpress.com/journal/JIN/23/10/10.31083/j.jin2310184/htm

  ASD-like symptoms may be related to synaptic dysfunction, and hence the role of genes related to synaptic function has received widespread attention in the pathogenesis of ASD. […] Therefore, developmental disorders and dysfunction of synapses may play an essential role in the pathogenesis of ASD. […] These findings suggest that dysfunctional synaptic transmission and E/I imbalance represent a baseline pathological mechanism for ASD. […] Different genetic variants share a common molecular pathway. […] This approach should deepen our comprehension of ASD and also facilitate the development of tailored interventions that could significantly improve the quality of life of those affected by this condition.

• #27 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Reduced NMDA receptor function has been linked to reduced social interactions, locomotor hyperactivity, self-injury, prepulse inhibition (PPI) deficits, and sensory hypersensitivity, among others. Results suggest that NMDA dysregulation could contribute to core ASD symptoms. […] Several lines of evidence indicate abnormalities of folate metabolism in ASD. These abnormalities can lead to a decrease in 5-methyltetrahydrofolate production, alter the production of folate metabolites and reduce folate transport across the blood-brain barrier and in neurons. The most significant abnormalities of folate metabolism associated with ASD may be autoantibodies to the alpha folate receptor (FR). These autoantibodies have been associated with cerebral folate deficiency.

• #28 SFARI | Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders

  https://www.sfari.org/funded-project/parvalbumin-down-regulation-as-a-common-pathophysiological-mechanism-in-autism-spectrum-disorders/

  Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders […] Although a strong genetic component is evident in the etiology of autism spectrum disorders (ASD), mutations in any given ASD susceptibility gene account for less than 1% of ASD cases. Fully understanding the biological complexity of ASD will require the identification of common and unifying dysfunctions/pathways underlying the core ASD symptoms. […] A large body of evidence suggests that impairments in neuronal excitatory/inhibitory (E/I) balance play a role in ASD pathology and altered functioning of the parvalbumin (PV)-expressing subgroup of GABAergic interneurons is a common cause of E/I imbalance. PV-immunoreactive (PV+) neurons have been shown to be decreased in postmortem brain tissue of individuals affected by ASD, and PV mRNA is among the most strongly downregulated transcripts in ASD. Further, several ASD mouse models, including Shank3, Shank1 and Cntnap2 knockout mice exhibit a downregulation of PV expression levels in various brain regions. Combined, these data suggest that downregulation of PV expression may represent a pathogenic molecular hub for ASD.

• #29 SFARI | Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders

  https://www.sfari.org/funded-project/parvalbumin-down-regulation-as-a-common-pathophysiological-mechanism-in-autism-spectrum-disorders/

  Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders […] Although a strong genetic component is evident in the etiology of autism spectrum disorders (ASD), mutations in any given ASD susceptibility gene account for less than 1% of ASD cases. Fully understanding the biological complexity of ASD will require the identification of common and unifying dysfunctions/pathways underlying the core ASD symptoms. […] A large body of evidence suggests that impairments in neuronal excitatory/inhibitory (E/I) balance play a role in ASD pathology and altered functioning of the parvalbumin (PV)-expressing subgroup of GABAergic interneurons is a common cause of E/I imbalance. PV-immunoreactive (PV+) neurons have been shown to be decreased in postmortem brain tissue of individuals affected by ASD, and PV mRNA is among the most strongly downregulated transcripts in ASD. Further, several ASD mouse models, including Shank3, Shank1 and Cntnap2 knockout mice exhibit a downregulation of PV expression levels in various brain regions. Combined, these data suggest that downregulation of PV expression may represent a pathogenic molecular hub for ASD.

• #30 SFARI | Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders

  https://www.sfari.org/funded-project/parvalbumin-down-regulation-as-a-common-pathophysiological-mechanism-in-autism-spectrum-disorders/

  In further support of this hypothesis, PV+/- and PV-/- mice exhibit repetitive behaviors and deficits in social behaviors; 17-b estradiol-mediated upregulation of PV in the PV+/- mice was shown to significantly attenuate these behaviors. Beat Schwallers laboratory thus argues that upregulating PV expression might serve as a useful therapeutic approach for ASD. […] To address this systematically, Schwallers laboratory will take advantage of a transgenic mouse model in which PV expression can be modulated in a temporally precise manner. PV levels will be decreased at different time points during postnatal development, and behaviors will be assessed to see whether any changes in ASD core symptoms are observed. These experiments are expected to reveal windows of opportunities with respect to time periods of PV upregulation that may prove therapeutically beneficial for ASD.

• #31 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Previous omics studies have also revealed that physiological and metabolic abnormalities such as mitochondrial dysfunction, oxidation, and inflammation are associated with ASD. The mitochondrial deficiency is expected to explain the underlying damage mechanism in ASD. ASD were described as mitochondrial diseases and its potential mechanism was identified through phosphoproteomics. […] The search for commonalities among children with ASD has become a focus of current research and a breakthrough point. ASDrelated syndromes with a clear genetic cause for the autism phenotype offer the best opportunity to elucidate the underlying mechanisms of ASD and to identify possible therapeutic targets and diagnostic markers. […] The comorbidities in most children with ASD is a notable attribute, contributing to its diverse and intricate nature. Thus, investigating common mechanisms between ASD and comorbidities, as well as the specific genes and mechanisms that lead to their respective occurrence, is a topic of interest in the field of ASD research, and its study contributes to the diagnosis and treatment of ASD. […] As mentioned above, immune dysregulation, inflammation, oxidative stress, and mitochondrial dysfunction are closely associated with ASD and are important physiological and metabolic abnormalities in ASD. They may be the intersection of genetic and environmental factors and contribute to ASD.

• #32 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Previous omics studies have also revealed that physiological and metabolic abnormalities such as mitochondrial dysfunction, oxidation, and inflammation are associated with ASD. The mitochondrial deficiency is expected to explain the underlying damage mechanism in ASD. ASD were described as mitochondrial diseases and its potential mechanism was identified through phosphoproteomics. […] The search for commonalities among children with ASD has become a focus of current research and a breakthrough point. ASDrelated syndromes with a clear genetic cause for the autism phenotype offer the best opportunity to elucidate the underlying mechanisms of ASD and to identify possible therapeutic targets and diagnostic markers. […] The comorbidities in most children with ASD is a notable attribute, contributing to its diverse and intricate nature. Thus, investigating common mechanisms between ASD and comorbidities, as well as the specific genes and mechanisms that lead to their respective occurrence, is a topic of interest in the field of ASD research, and its study contributes to the diagnosis and treatment of ASD. […] As mentioned above, immune dysregulation, inflammation, oxidative stress, and mitochondrial dysfunction are closely associated with ASD and are important physiological and metabolic abnormalities in ASD. They may be the intersection of genetic and environmental factors and contribute to ASD.

• #33 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  Previous omics studies have also revealed that physiological and metabolic abnormalities such as mitochondrial dysfunction, oxidation, and inflammation are associated with ASD. The mitochondrial deficiency is expected to explain the underlying damage mechanism in ASD. ASD were described as mitochondrial diseases and its potential mechanism was identified through phosphoproteomics. […] The search for commonalities among children with ASD has become a focus of current research and a breakthrough point. ASDrelated syndromes with a clear genetic cause for the autism phenotype offer the best opportunity to elucidate the underlying mechanisms of ASD and to identify possible therapeutic targets and diagnostic markers. […] The comorbidities in most children with ASD is a notable attribute, contributing to its diverse and intricate nature. Thus, investigating common mechanisms between ASD and comorbidities, as well as the specific genes and mechanisms that lead to their respective occurrence, is a topic of interest in the field of ASD research, and its study contributes to the diagnosis and treatment of ASD. […] As mentioned above, immune dysregulation, inflammation, oxidative stress, and mitochondrial dysfunction are closely associated with ASD and are important physiological and metabolic abnormalities in ASD. They may be the intersection of genetic and environmental factors and contribute to ASD.

• #34 Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach | IntechOpen

  https://www.intechopen.com/chapters/79122

  Mitochondrial abnormalities include either decreased or increased mitochondrial function; depending on the cause and developmental time window, they may lead to neurodevelopmental regression and the typical comorbidities of ASD (i.e., gastrointestinal problems, seizures, tiredness, and sensory dysregulation). […] Neurodevelopmental regression, as typically described for many children with ASD, may be the hallmark of a mitochondrial disorder and abnormal mitochondrial physiology in ASD. […] As mitochondrial function is highly influenced by environmental factors, these findings connect mitochondrial dysfunction in ASD with environmental hazards.

• #35 Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach | IntechOpen

  https://www.intechopen.com/chapters/79122

  Mitochondrial abnormalities include either decreased or increased mitochondrial function; depending on the cause and developmental time window, they may lead to neurodevelopmental regression and the typical comorbidities of ASD (i.e., gastrointestinal problems, seizures, tiredness, and sensory dysregulation). […] Neurodevelopmental regression, as typically described for many children with ASD, may be the hallmark of a mitochondrial disorder and abnormal mitochondrial physiology in ASD. […] As mitochondrial function is highly influenced by environmental factors, these findings connect mitochondrial dysfunction in ASD with environmental hazards.

• #36 Autism Spectrum Disorder (ASD): From Molecular Mechanism to Novel Therapeutic Approach | IntechOpen

  https://www.intechopen.com/chapters/79122

  Mitochondrial abnormalities include either decreased or increased mitochondrial function; depending on the cause and developmental time window, they may lead to neurodevelopmental regression and the typical comorbidities of ASD (i.e., gastrointestinal problems, seizures, tiredness, and sensory dysregulation). […] Neurodevelopmental regression, as typically described for many children with ASD, may be the hallmark of a mitochondrial disorder and abnormal mitochondrial physiology in ASD. […] As mitochondrial function is highly influenced by environmental factors, these findings connect mitochondrial dysfunction in ASD with environmental hazards.

• #37 A Review of Causes, Physiology, Immunity and Proposed Drug Strategies of Autism Spectrum Disorders

  https://asmj.journals.ekb.eg/article_339534.html

  Early infancy repetitive behavioural patterns and social communication issues are hallmarks of autism spectrum disorder (ASD). […] Numerous genetic, environmental, and immunological variables are thought to have a role in the pathogenesis of ASD, but its etiology has remained a mystery in spite of intensive research. […] ASD pathogenesis has been linked to a number of genes related to synaptogenesis in neurons. […] Additionally, environmental elements and ailments like immunological imbalances and gastrointestinal (GI) abnormalities have been connected to the pathogenesis of ASD. […] Given the strong relationship between the immune system and the GI tract, abnormal immunological responses seen in autistic children may be caused by autoimmune diseases or infections in the mother. […] Furthermore, ASD has frequently been linked to mitochondrial malfunction, a common metabolic condition. […] It is thought that oxidative stress, a characteristic of many neurological illnesses, contributes to the development or occurrence of autism and autonomic dysfunction.

• #38 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  ASD is hypothesized to be caused by oxidative stress. […] Diminished neuronal activity indicated by reductions of NAA in frontal, parietal, and temporal lobes, amygdala, hippocampus, and thalamus of children with ASD was observed on MRS. […] In animal studies, dysfunction of serotonin and the neuropeptides oxytocin and vasopressin has been associated with abnormalities in affiliative behaviors. […] Elevations of blood serotonin levels occur in approximately one third of individuals with ASD and are also reported in the parents and siblings of patients. […] Immunologic studies have identified abnormalities such as decreased plasma concentrations of the C4B complement protein. Such abnormalities may be the source of the increased susceptibility to infection seen in some people with ASD.

• #39 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  Synaptic dysfunction also appears to be implicated in autism, with some mutations disrupting synaptic pathways involving cell adhesion. Evidence points to teratogens affecting the early developmental stages, suggesting autism arises very early, possibly within the first eight weeks after conception. […] Neuroanatomical studies support that autism may involve abnormal neuronal growth and pruning, leading to brain enlargement in some areas and reduction in others. […] The immune system is thought to play an important role in autism. Children with autism have been found by researchers to have inflammation of both the peripheral and central immune systems as indicated by increased levels of pro-inflammatory cytokines and significant activation of microglia. […] Some evidence suggests that gut-brain axis abnormalities may be involved by means of impaired serotonin signaling and inflammation. A 2015 review proposed that immune dysregulation, gastrointestinal inflammation, autonomic nervous system malfunction, gut microbiota alterations, and food metabolites may cause brain neuroinflammation and dysfunction.

• #40 Pathogenesis of Brain: Autism Spectrum Disorders | Auctores

  https://auctoresonline.org/article/pathogenesis-of-brain-autism-spectrum-disorders

  Pathogenesis of Brain: Autism Spectrum Disorders […] Autism spectrum disorders (ASDs) affect as many as 1 in 45 children and are characterized by deficits in sociability and communication, as well as stereotypic movements. Many children also show severe anxiety. […] The lack of distinct pathogenesis and reliable biomarkers hampers the development of effective treatments. As a result, most children with ASD are prescribed psychopharmacologic agents that do not address the core symptoms of ASD. Autoantibodies against brain epitopes in mothers of children with ASD and many such children strongly correlate with allergic symptoms and indicate an aberrant immune response, as well as disruption of the blood-brain barrier (BBB). Recent epidemiological studies have shown a strong statistical correlation between risk for ASD and either maternal or infantile atopic diseases, such as asthma, eczema, food allergies and food intolerance, all of which involve activation of mast cells (MCs). These unique tissue immune cells are located perivascularly in all tissues, including the thalamus and hypothalamus, which regulate emotions. MC-derived inflammatory and vasoactive mediators increase BBB permeability. Expression of the inflammatory molecules interleukin (IL-1), IL-6, 1L-17 and tumor necrosis factor (TNF) is increased in the brain, cerebrospinal fluid and serum of some patients with ASD, while NF-kB is activated in brain samples and stimulated peripheral blood immune cells of other patients; however, these molecules are not specific. Instead the peptide neurotensin is uniquely elevated in the serum of children with ASD, as is corticotropin-releasing hormone, secreted from the hypothalamus under stress. Both peptides trigger MC to release IL-6 and TNF, which in turn, stimulate microglia proliferation and activation, leading to disruption of neuronal connectivity. MC-derived IL-6 and TGF induce maturation of Th17 cells and MCs also secrete IL-17, which is increased in ASD. Serum IL-6 and TNF may define an ASD subgroup that benefits most from treatment with the natural flavonoid luteolin. Atopic diseases may create a phenotype susceptible to ASD and formulations targeting focal inflammation of the brain could have great promise in the treatment of ASD. […] Recent studies have shown strong associations between allergies, asthma, autoimmune diseases and psoriasis in the mother with increased risk for ASD in their children. Moreover, mothers with mastocytosis or MC activation syndrome were much more likely to have children who developed ASD.

• #41 Mechanism of autism – Wikipedia

  https://en.wikipedia.org/wiki/Mechanism_of_autism

  The mechanisms of autism are the molecular and cellular processes believed to cause or contribute to the symptoms of autism. Multiple processes are hypothesized to explain different autism spectrum features. These hypotheses include defects in synapse structure and function, reduced synaptic plasticity, disrupted neural circuit function, gut-brain axis dyshomeostasis, neuroinflammation, and altered brain structure or connectivity. Autism symptoms stem from maturation-related changes in brain systems. The mechanisms of autism are divided into two main areas: pathophysiology of brain structures and processes, and neuropsychological linkages between brain structures and behaviors, with multiple pathophysiologies linked to various autism behaviors. […] Evidence suggests gut-brain axis abnormalities may contribute to autism. Studies propose that immune, gastrointestinal inflammation, autonomic nervous system dysfunction, gut microbiota alterations, and dietary metabolites may contribute to brain neuroinflammation and dysfunction. Additionally, enteric nervous system abnormalities could play a role in neurological disorders by allowing disease pathways from the gut to impact the brain.

• #42 Autism Spectrum Disorder Pathogenesis—A Cross-Sectional Literature Review Emphasizing Molecular Aspects

  https://www.mdpi.com/1422-0067/25/20/11283

  The relationship between the gut environment and the brain (microbiome–gut–brain axis) has been seen as an important factor in modulating brain maturation and functioning, but its detailed contribution to ASD etiology is not well understood. […] The discussion about the ASD pathway has focused on the gut–brain axis for many years. […] Many studies presented a dependence of ASD symptoms on gut dysbiosis. […] It is believed that bidirectional communication between the gut and the brain is via vagal fibers and gut neurotransmitters. […] A few studies investigating other ASD causes in diet or environmental associations focus on mercury and biphenyl poisoning as a potential ASD cause. […] The signaling pathway of lipid molecules contributes to the pathophysiology of autism spectrum disorder (ASD) and provides hope for alternative therapeutic strategies.

• #43 Autism Spectrum Disorder Pathogenesis—A Cross-Sectional Literature Review Emphasizing Molecular Aspects

  https://www.mdpi.com/1422-0067/25/20/11283

  The relationship between the gut environment and the brain (microbiome–gut–brain axis) has been seen as an important factor in modulating brain maturation and functioning, but its detailed contribution to ASD etiology is not well understood. […] The discussion about the ASD pathway has focused on the gut–brain axis for many years. […] Many studies presented a dependence of ASD symptoms on gut dysbiosis. […] It is believed that bidirectional communication between the gut and the brain is via vagal fibers and gut neurotransmitters. […] A few studies investigating other ASD causes in diet or environmental associations focus on mercury and biphenyl poisoning as a potential ASD cause. […] The signaling pathway of lipid molecules contributes to the pathophysiology of autism spectrum disorder (ASD) and provides hope for alternative therapeutic strategies.

• #44 Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance

  https://www.wjgnet.com/1007-9327/full/v20/i29/9942.htm

  Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. […] Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. […] A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. […] Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. […] Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections.

• #45 Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance

  https://www.wjgnet.com/1007-9327/full/v20/i29/9942.htm

  GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. […] Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. […] In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions. […] The exact pathomechanism of ASD is not known so far while several factors have been implicated in its pathogenesis of autistic disorders. […] Among these, the genetic cause has long been implicated to be a strong evidence-based etiology in cases of some co-occurring or associated conditions with ASD such as tuberous sclerosis, fragile X syndrome, Rett syndrome and some other.

• #46

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. […] The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD.

• #47

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder. […] Inflammatory deviations are potential etiology candidates in how gut microbiota can influence the gut-brain axis of ASD patients. Neuroinflammatory factors in ASD result from changes in the regulation of intestinal barriers, activation and function of microglia, and levels of neurotransmitters.

• #48 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The etiology of ASD is extremely complex. Twin studies suggest that genes play a key role in the pathogenesis of ASD, and its heritability estimates range from 64% to 91%. In families with children with ASD, the average rate of ASD recurrence is estimated to be 15%25% for male newborns and 5%15% for female newborns. Besides, environmental factors are also implicated in the development of ASD, including prenatal/perinatal, microbialgutbrain axis, and others. Prenatal/perinatal causes included maternal age 35 years, maternal characteristics of metabolic syndrome, use of antidepressant valproic acid (VPA) medications, and the effects of infection and inflammation. Environmental factors can directly influence specific susceptibility genes, prompting epigenetic modifications such as DNA methylation and histone changes (phosphorylation and acetylation), which increase the risk of developing ASD. ASD arises from a complex interplay of genetic and environmental factors, leading to changes in brain structure and function that manifest as behavioral abnormalities.

• #49 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The etiology of ASD is extremely complex. Twin studies suggest that genes play a key role in the pathogenesis of ASD, and its heritability estimates range from 64% to 91%. In families with children with ASD, the average rate of ASD recurrence is estimated to be 15%25% for male newborns and 5%15% for female newborns. Besides, environmental factors are also implicated in the development of ASD, including prenatal/perinatal, microbialgutbrain axis, and others. Prenatal/perinatal causes included maternal age 35 years, maternal characteristics of metabolic syndrome, use of antidepressant valproic acid (VPA) medications, and the effects of infection and inflammation. Environmental factors can directly influence specific susceptibility genes, prompting epigenetic modifications such as DNA methylation and histone changes (phosphorylation and acetylation), which increase the risk of developing ASD. ASD arises from a complex interplay of genetic and environmental factors, leading to changes in brain structure and function that manifest as behavioral abnormalities.

• #50 Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10908366/

  The etiology of ASD is extremely complex. Twin studies suggest that genes play a key role in the pathogenesis of ASD, and its heritability estimates range from 64% to 91%. In families with children with ASD, the average rate of ASD recurrence is estimated to be 15%25% for male newborns and 5%15% for female newborns. Besides, environmental factors are also implicated in the development of ASD, including prenatal/perinatal, microbialgutbrain axis, and others. Prenatal/perinatal causes included maternal age 35 years, maternal characteristics of metabolic syndrome, use of antidepressant valproic acid (VPA) medications, and the effects of infection and inflammation. Environmental factors can directly influence specific susceptibility genes, prompting epigenetic modifications such as DNA methylation and histone changes (phosphorylation and acetylation), which increase the risk of developing ASD. ASD arises from a complex interplay of genetic and environmental factors, leading to changes in brain structure and function that manifest as behavioral abnormalities.

• #51

  https://neurolaunch.com/pathophysiology-of-autism/

  Early brain development is crucial in the pathogenesis of ASD. […] Critical periods in ASD pathogenesis refer to specific windows of time during development when the brain is particularly sensitive to environmental inputs and experiences. […] The concept of neurodiversity in understanding ASD has gained traction in recent years. […] The multifactorial nature of ASD etiology is now widely recognized. […] The interaction between genetic predisposition and environmental triggers is a key area of research in ASD etiology. […] Several proposed models for autism pathogenesis attempt to integrate the diverse findings in ASD research. […] In summary, the pathophysiology of autism spectrum disorder involves a complex interplay of genetic, environmental, and developmental factors. Key findings include abnormalities in brain structure and connectivity, neurochemical imbalances, synaptic dysfunction, and immune system irregularities.

• #52 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  Among the environmental factors that have an impact on ASD onset and act in the developmental phases, there are several maternal-related determinants including maternal nutrition, hormonal equilibrium, and stress status, as well as substance abuse and exposure to environmental chemicals, including air pollutants, pesticides, plastics derivatives, and metals. […] A further level of complexity of gene environment (GE) interactions recently emerged from a study performed on a cohort of twins including typically developed (TD) individuals and ASD patients. […] Finally, another mechanism underlying the convergence between genetic predisposition and environmental exposure is the interference of the latter with the regulation of the expression of the genes involved in key molecular pathways often disrupted in NDDs.

• #53 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  In fact, mutations in chromatin regulators and transcription factors figure prominently among the most common genetic causes of NDDs, with more than 150 of them listed in the Simons Foundation Autism Risk Initiative (SFARI) database. […] Given its pervasive nature and its ability to influence the early phases of fetal development, the potential effect of environmental chemical exposure is gaining increasing attention. […] However, an accurate and exhaustive estimation of the burden related to chemical substances on the manifestation of NDDs is particularly challenging considering that the current real-life scenario encompasses long-term exposures to a complex mix of substances that could interact in intricate ways among themselves and with individual genetic factors. […] The developing CNS is particularly vulnerable to external insults.

• #54 Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

  https://www.cpn.or.kr/journal/view.html?uid=176&vmd=Full&

  Some articles emphasized that rising levels of autism could be related to environmental exposure to toxins. […] It is estimated that ASD children have impaired methylation, sulfation and anti-oxidant processes associated with the detoxification process of heavy metals. […] Oral vitamin supplementation is beneficial in improving the nutritional and metabolic status of children with ASDs. […] Despite the limitations of the studies, the cumulative findings suggest that chelation might be a viable form of treatment in some individuals with an ASD who have elevated heavy metal content or biochemical changes. […] Pharmacotherapy in patients with ASD is focused on immediate problems in everyday life such as, anxiety, seizures, hyperactivity, aggressive behavior, self-harm and stereotypy. […] Etiological pharmacotherapy, in addition to conservative treatment, is necessary. […] Although some medications based on neurotransmitter hypothesis such as cholinergic and glutamatergic reveals as effective drug and some of the treatments stands out mostly as an adjuvant therapy, some have no relation whatsoever regarding effects and pathogenesis.

• #55 Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01081-0

  In this review, we integrate recent advances from genetic, neuropathological, and neurobiochemical studies on ASD to further elucidate the pathogenetic mechanism at the molecular, cellular, and neural circuit levels. […] ASD is considered to be the result of complex interactions among genetic, environmental, and immunological factors. […] The genetic structure of ASD is extremely complex. […] The genetic contribution of ASD results from the combination of rare deleterious variants and a large number of low-risk alleles. […] The first category is the dysregulation of important transcripts and translational signalling pathways. […] The second category involves synaptic proteins, including cell adhesion, scaffolding, and signalling molecules, which can affect synapse structure and function during different processes of synapse formation, elimination, transmission, and plasticity.

• #56 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. […] Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. […] Here, we will focus on ASD as a paradigmatic example of NDD whose manifestation is the outcome of a complex interaction of predisposition factors and genetic or environmental lesions. We will elucidate how both genetic alterations and toxic insults can be at the root of the pathogenetic events that trigger NDDs, highlighting the growing body of evidence pointing towards an interplay between the individual genetic make-up and the environmental exposures occurring in early life, and their convergence towards key molecular pathways.

• #57 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  Among the environmental factors that have an impact on ASD onset and act in the developmental phases, there are several maternal-related determinants including maternal nutrition, hormonal equilibrium, and stress status, as well as substance abuse and exposure to environmental chemicals, including air pollutants, pesticides, plastics derivatives, and metals. […] A further level of complexity of gene environment (GE) interactions recently emerged from a study performed on a cohort of twins including typically developed (TD) individuals and ASD patients. […] Finally, another mechanism underlying the convergence between genetic predisposition and environmental exposure is the interference of the latter with the regulation of the expression of the genes involved in key molecular pathways often disrupted in NDDs.

• #58 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  Among the environmental factors that have an impact on ASD onset and act in the developmental phases, there are several maternal-related determinants including maternal nutrition, hormonal equilibrium, and stress status, as well as substance abuse and exposure to environmental chemicals, including air pollutants, pesticides, plastics derivatives, and metals. […] A further level of complexity of gene environment (GE) interactions recently emerged from a study performed on a cohort of twins including typically developed (TD) individuals and ASD patients. […] Finally, another mechanism underlying the convergence between genetic predisposition and environmental exposure is the interference of the latter with the regulation of the expression of the genes involved in key molecular pathways often disrupted in NDDs.

• #59 Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology | Molecular Autism | Full Text

  https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00370-1

  Our recent experiments performed on human neurodevelopmental models revealed that the specific mixture of EDCs that was associated to neurodevelopmental outcomes at the epidemiological level has a transcriptional impact on the same genes whose mutations are causative of ASD. […] In summary, a growing body of evidence is accumulating indicating an interplay between genetic and environmental factors in ASD pathogenesis.

• #60 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #61 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #62 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy specimens of some children with ASD, compared with those without ASD. […] Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with ASD compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with ASD and related conditions.

• #63 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #64 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #65 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms. For example, social and language deficits of people with ASD likely are related to dysfunction of the frontal and temporal lobes. […] In a study of postmortem brain tissue from 11 children with ASD and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with ASD and 1 of the controls, suggesting that brain irregularities in ASD may have prenatal origins. […] The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.

• #66 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #67 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #68 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #69 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  On MRI scans, the brains of children with ASD demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. […] Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism. […] Reductions in cerebral GABA likely contribute to the sensorimotor and behavioral anomalies of individuals with ASD. […] Postmortem specimens of the brains of people with ASD demonstrated reductions for gamma-aminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.

• #70 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  ASD is hypothesized to be caused by oxidative stress. […] Diminished neuronal activity indicated by reductions of NAA in frontal, parietal, and temporal lobes, amygdala, hippocampus, and thalamus of children with ASD was observed on MRS. […] In animal studies, dysfunction of serotonin and the neuropeptides oxytocin and vasopressin has been associated with abnormalities in affiliative behaviors. […] Elevations of blood serotonin levels occur in approximately one third of individuals with ASD and are also reported in the parents and siblings of patients. […] Immunologic studies have identified abnormalities such as decreased plasma concentrations of the C4B complement protein. Such abnormalities may be the source of the increased susceptibility to infection seen in some people with ASD.

• #71 Autism Spectrum Disorder: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/912781-overview

  ASD is hypothesized to be caused by oxidative stress. […] Diminished neuronal activity indicated by reductions of NAA in frontal, parietal, and temporal lobes, amygdala, hippocampus, and thalamus of children with ASD was observed on MRS. […] In animal studies, dysfunction of serotonin and the neuropeptides oxytocin and vasopressin has been associated with abnormalities in affiliative behaviors. […] Elevations of blood serotonin levels occur in approximately one third of individuals with ASD and are also reported in the parents and siblings of patients. […] Immunologic studies have identified abnormalities such as decreased plasma concentrations of the C4B complement protein. Such abnormalities may be the source of the increased susceptibility to infection seen in some people with ASD.

• #72 Autism spectrum disorder: Pathogenesis, biomarker, and intervention therapy

  https://medicalxpress.com/news/2024-04-autism-spectrum-disorder-pathogenesis-biomarker.html

  Although specific diagnostic markers for ASD have not yet been obtained, studies including high-throughput omics have shown convergence of mechanisms associated with them, usually focusing on a few categories. Therefore, there remains optimism regarding the identification of specific diagnostic biomarkers. […] Currently, there is still a lack of drugs to treat the core symptoms of ASD. The authors provide an overview of existing pharmacologic therapies for ASD as well as those that target its common pathophysiology and gut microbiota.

• #73 Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

  https://www.cpn.or.kr/journal/view.html?volume=12&number=1&spage=19

  Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social skills, communication deficits and repetitive behaviors, interests or activities. […] Although genetic predisposition and environmental contributors have been implicated in the pathophysiology of ASD, the precise mechanisms underlying the pathophysiology of this disorder remain unknown and there are no established methods of prevention or cure. […] A way to maximize the advantages of such changes as a single disorder would be to investigate the etiology and pathogenesis by medication. […] Recent animal studies show the amelioration of autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference, and enhancing social interaction through the augmentation of Ach in the synaptic cleft by inhibiting acetylcholinesterase.

• #74 Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

  https://www.cpn.or.kr/journal/view.html?volume=12&number=1&spage=19

  Several mechanisms related to a hyperglutamatergic hypothesis of autism are being proposed. […] There are proposals suggesting that glutamate transporters (excitatory amino acid transporters), which translocate glutamate from endothelial cells to the extracellular fluids, are involved in autism’s pathophysiology. […] Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with 2-methyl-6-(phenylethynyl) pyridine treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed rat offspring used as an animal model of ASD. […] Some articles emphasized that rising levels of autism could be related to environmental exposure to toxins. […] It is estimated that ASD children have impaired methylation, sulfation and anti-oxidant processes associated with the detoxification process of heavy metals.

• #75 Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

  https://www.cpn.or.kr/journal/view.html?volume=12&number=1&spage=19

  Several mechanisms related to a hyperglutamatergic hypothesis of autism are being proposed. […] There are proposals suggesting that glutamate transporters (excitatory amino acid transporters), which translocate glutamate from endothelial cells to the extracellular fluids, are involved in autism’s pathophysiology. […] Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with 2-methyl-6-(phenylethynyl) pyridine treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed rat offspring used as an animal model of ASD. […] Some articles emphasized that rising levels of autism could be related to environmental exposure to toxins. […] It is estimated that ASD children have impaired methylation, sulfation and anti-oxidant processes associated with the detoxification process of heavy metals.

• #76 SFARI | Parvalbumin down-regulation as a common pathophysiological mechanism in autism spectrum disorders

  https://www.sfari.org/funded-project/parvalbumin-down-regulation-as-a-common-pathophysiological-mechanism-in-autism-spectrum-disorders/

  In further support of this hypothesis, PV+/- and PV-/- mice exhibit repetitive behaviors and deficits in social behaviors; 17-b estradiol-mediated upregulation of PV in the PV+/- mice was shown to significantly attenuate these behaviors. Beat Schwallers laboratory thus argues that upregulating PV expression might serve as a useful therapeutic approach for ASD. […] To address this systematically, Schwallers laboratory will take advantage of a transgenic mouse model in which PV expression can be modulated in a temporally precise manner. PV levels will be decreased at different time points during postnatal development, and behaviors will be assessed to see whether any changes in ASD core symptoms are observed. These experiments are expected to reveal windows of opportunities with respect to time periods of PV upregulation that may prove therapeutically beneficial for ASD.

• #77

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Biomarkers based on neuroinflammatory processes associated with gut microbiota may provide a more objective and precise way of detecting ASD. […] Overall, gut microbiota seems to play a crucial role in ASD through inflammation. […] The changes in Gut microbiota-host interaction could induce miR-146a and consequently promote neuroinflammatory pathways. […] Overall, these findings support that probiotics may serve as a promising therapy due to their beneficial impact on symptoms of ASD.

• #78

  https://link.springer.com/article/10.1007/s10753-024-02061-y

  Biomarkers based on neuroinflammatory processes associated with gut microbiota may provide a more objective and precise way of detecting ASD. […] Overall, gut microbiota seems to play a crucial role in ASD through inflammation. […] The changes in Gut microbiota-host interaction could induce miR-146a and consequently promote neuroinflammatory pathways. […] Overall, these findings support that probiotics may serve as a promising therapy due to their beneficial impact on symptoms of ASD.

• #79 Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis? | springermedizin.de

  https://www.springermedizin.de/gut-microbiota-and-autism-spectrum-disorder-a-neuroinflammatory-/27423310

  Inflammatory deviations are potential etiology candidates in how gut microbiota can influence the gut-brain axis of ASD patients. Neuroinflammatory factors in ASD result from changes in the regulation of intestinal barriers, activation and function of microglia, and levels of neurotransmitters. […] Biomarkers based on neuroinflammatory processes associated with gut microbiota may provide a more objective and precise way of detecting ASD. Several examples of these markers include microRNAs that modulate immune signaling; brain-derived neurotrophic factor (BDNF), which promotes brain growth; S100B, which reflects neural immunity; and chemokines that facilitate immunological activation, such as RANTES and eotaxin. […] Overall, gut microbiota seems to play a crucial role in ASD through inflammation. […] The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

• #80

  https://benthamscience.com/public/article/128339

  Autism spectrum disorder (ASD) is a cluster of heterogeneous neurodevelopmental conditions with atypical social communication and repetitive sensory-motor behaviors. […] Accumulating evidence sheds light on how the deficits in the hippocampal neurogenesis may underlie some of the abnormal behavioral phenotypes in ASD. […] In this review, we describe the current evidence concerning pre-clinical and clinical studies supporting the significant role of hippocampal neurogenesis in ASD pathogenesis, discuss the possibility of improving hippocampal neurogenesis as a new strategy for treating ASD, and highlight the prospect of emerging proneurogenic therapies for ASD.

• #81 Molecular pathogenesis of autism spectrum disorder using human disease models – Brain/MINDS 2.0

  https://brainminds.jp/en/research/1944

  Molecular pathogenesis of autism spectrum disorder using human disease models […] Recently, the chromatin remodeling factor CHD8 has been identified as the most promising candidate gene for ASD. […] We have generated mice that replicate the CHD8 mutation observed in individuals with ASD and demonstrated that these mice exhibit ASD-like symptoms due to delayed neurogenesis and abnormalities in neural circuits. […] In this study, we aim to identify cell populations involved in the development of ASD during neurogenesis and to characterize the neural circuits constructed by these cells, with the ultimate goal of developing evidence-based treatments.

• #82 When autism spectrum disorder occurs with intellectual disability, convergent mechanism for two top-ranking risk genes may be cause – UBNow: News and views for UB faculty and staff – University at Buffalo

  https://www.buffalo.edu/ubnow/campus.host.html/content/shared/university/news/ub-reporter-articles/stories/2022/07/autism-intellectual-disability.detail.html

  Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons. […] We found that changes in two risk genes lead to a convergent mechanism, likely involving immune activation, Conrow-Graham says. […] The researchers are hopeful that future work will determine whether chronic neuroinflammation could be directly contributing to at least some cases of ASD/ID, in which targeting microglia or inflammatory signaling pathways could prove to be a useful treatment.

• #83

  https://neurolaunch.com/pathophysiology-of-autism/

  Future directions in autism research are likely to include further exploration of gene-environment interactions, the role of the gut microbiome, and the potential of precision medicine approaches. […] The importance of continued study of ASD etiology for improved patient outcomes cannot be overstated.

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