ArticlePloS one2014
Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Targeting the cholinergic and endocannabinoid systems as a therapeutic intervention for core and associated phenotypes in the autism model; a systematic review.Trends in psychiatry and psychotherapy · 2025Pooled it
- Postmortem Studies of Neuroinflammation in Autism Spectrum Disorder: a Systematic Review.Molecular neurobiology · 2020Pooled it
- Protective Effects of PrenatalMolecules (Basel, Switzerland) · 2026Article
- A Novel Approach of Development of Robust Animal Model for Autism Spectrum Disorder.Annals of neurosciences · 2026Article
- Tamoxifen as a Therapeutic Intervention for Neurobehavioral Deficits in a Propionic Acid-Induced Autism Model via Anti-inflammatory Mechanisms.Neurochemical research · 2026Article
- Therapeutic Effects of MOTS-c in the Valproic Acid-Induced Autism Model in Rats: Role of Tetrahydrobiopterin and Brain-Derived Neurotrophic Factor.Molecular neurobiology · 2026Article
- Supplementation of aged garlic extract attenuates age-associated memory impairment and cognitive decline: Involvement of molecular pathways in the cortex and hippocampus.Biomedical reports · 2026Article
- Investigating the Effects of Vortioxetine in an Experimental Model of Autism Spectrum Disorder: Role of NOD-like Receptor Protein-3 Inflammasome Pathway.Psychiatry and clinical psychopharmacology · 2025Article
- Digestive Neurobiology in Autism: From Enteric and Central Nervous System Interactions to Shared Genetic Pathways.International journal of molecular sciences · 2025Review
- Sociability: Comparing the Effect of Chlorpyrifos with Valproic Acid.Journal of autism and developmental disorders · 2025Article
- tDCS-induced enhancement of cognitive flexibility in autism: role of frontal lobe and associated neural circuits.Frontiers in behavioral neuroscience · 2025Article
- Article
- Black seed oil reverses chronic antibiotic-mediated depression and social behaviour deficits via modulation of hypothalamic mitochondrial-dependent markers and insulin expression.IBRO neuroscience reports · 2024Article
- Long-Term Epigenetic Regulation ofInternational journal of molecular sciences · 2024Article
- Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets.Scientific reports · 2023Article
- Canagliflozin alleviates valproic acid-induced autism in rat pups: Role of PTEN/PDK/PPAR-γ signaling pathways.Frontiers in pharmacology · 2023Article
- Testing the extreme male hypothesis in the valproate mouse model; sex-specific effects on plasma testosterone levels and tyrosine hydroxylase expression in the anteroventral periventricular nucleus, but not on parental behavior.Frontiers in behavioral neuroscience · 2023Article
- The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Photobiomodulation Attenuated Cognitive Dysfunction and Neuroinflammation in a Prenatal Valproic Acid-Induced Autism Spectrum Disorder Mouse Model.International journal of molecular sciences · 2022Article
- Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases.Iranian journal of pharmaceutical research : IJPR · 2022Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.
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Registered trials
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.