ArticleActa neuropathologica communications2015
Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid.
Article in Acta neuropathologica communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.
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Who cites it
55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Animal studies reveal downregulation of the Beclin-1 autophagy pathway as shared mechanism in Autism Spectrum Disorder: a systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer.Molecular autism · 2019Pooled it
- Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined-samples mega-analysis.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Pooled it
- Article
- Gestational Paracetamol (Acetaminophen) Toxicity Induces Behavioral and Structural Brain Defects in Rats.Current issues in molecular biology · 2026Article
- Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice.Molecular psychiatry · 2026Article
- Untargeted metabolomics and proteomics reveals cocoa-mediated mitigation of valproic acid-induced dysregulation in a zebrafish model of autism: pilot study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Copper deficiency impairs oligodendrocyte maturation and social behavior via mitophagy and mTOR suppression in ASD.Science advances · 2026Article
- VGLUT1 and PSD-95 Expression Remains Stable in the Prefrontal and Cerebellar Cortices of the VPA Autism Rat Model.Developmental neurobiology · 2026Article
- Chrysin Ameliorates Valproic Acid Induced Autism Spectrum Behavioral Phenotypes Through Corticohippocampal Histone Deacetylase and Translational Modulation of SHANK3 Expression in Juvenile Rats.Journal of molecular neuroscience : MN · 2026Article
- Targeting the mTOR Pathway with Natural Products: A Potential Therapeutic Approach for Autism Spectrum Disorders.Current neuropharmacology · 2026Review
- Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.Frontiers in immunology · 2026Review
- Dissociation of the mTOR Protein Interaction Network Following Neuronal Activation Is Altered by Shank3 Mutation.Journal of neurochemistry · 2026Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses.Neurochemical research · 2025Review
- ESC models of autism with copy-number variations reveal cell-type-specific translational vulnerability.Cell genomics · 2025Article
- Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders.Brain sciences · 2025Review
- Impaired macroautophagy confers substantial risk for intellectual disability in children with autism spectrum disorders.Molecular psychiatry · 2025Article
- Neurodevelopmental disorders and gut-brain interactions: exploring the therapeutic potential of pycnogenol through microbial-metabolic-neural networks.Frontiers in cellular and infection microbiology · 2025Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe molecular mechanisms underlying autistic behaviors remain to be elucidated. Mutations in genes linked to autism adversely affect molecules regulating dendritic spine formation, function and plasticity, and some increase the mammalian target of rapamycin, mTOR, a regulator of protein synthesis at spines. Here, we investigated whether the Akt/mTOR pathway is disrupted in idiopathic autism and in rats exposed to valproic acid, an animal model exhibiting autistic-like behavior.
methodsComponents of the mTOR pathway were assayed by Western blotting in postmortem fusiform gyrus samples from 11 subjects with idiopathic autism and 13 controls and in valproic acid versus saline-exposed rat neocortex. Additionally, protein levels of brain-derived neurotrophic factor receptor (TrkB) isoforms and the postsynaptic organizing molecule PSD-95 were measured in autistic versus control subjects.
resultsFull-length TrkB, PI3K, Akt, phosphorylated and total mTOR, p70S6 kinase, eIF4B and PSD-95 were reduced in autistic versus control fusiform gyrus. Similarly, phosphorylated and total Akt, mTOR and 4E-BP1 and phosphorylated S6 protein were decreased in valproic acid- versus saline-exposed rats. However, no changes in 4E-BP1 or eIF4E were found in autistic brains.
conclusionsIn contrast to some monogenic disorders with high rates of autism, our data demonstrate down-regulation of the Akt/mTOR pathway, specifically via p70S6K/eIF4B, in idiopathic autism. These findings suggest that disruption of this pathway in either direction is widespread in autism and can have adverse consequences for synaptic function. The use of valproic acid, a histone deacetylase inhibitor, in rats successfully modeled these changes, implicating an epigenetic mechanism in these pathway disruptions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.