ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
In Utero Exposure to Valproic Acid Induces Neocortical Dysgenesis via Dysregulation of Neural Progenitor Cell Proliferation/Differentiation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Craniofacial development: genetics, signaling pathways, teratogenic mechanisms, and clinal significance.Molecular biomedicine · 2026Review
- Defective Neural Stem and Progenitor Cell Proliferation in Neurodevelopmental Disorders.Journal of developmental biology · 2025Review
- Stage-Dependent Disruptions in Neurogenesis and Neurotrophins' Production Following Prenatal and Postnatal Valproic Acid Exposure: Implications for Autism Spectrum Disorders.Cellular and molecular neurobiology · 2025Article
- Cell villages and Dirichlet modeling map human cell fitness genetics.bioRxiv : the preprint server for biology · 2025Article
- The Differential Developmental Neurotoxicity of Valproic Acid on Anterior and Posterior Neural Induction of Human Pluripotent Stem Cells.International journal of stem cells · 2025Article
- Article
- Pre- and Postnatal Valproate Exposure Affects Brain Development.Current topics in behavioral neurosciences · 2025Review
- Delving into the Complexity of Valproate-Induced Autism Spectrum Disorder: The Use of Zebrafish Models.Cells · 2024Article
- Differences in the expression of cortex-wide neural dynamics are related to behavioral phenotype.Current biology : CB · 2024Article
- Prenatal Exposure to Antiseizure Medications and Risk of Epilepsy in Children of Mothers With Epilepsy.JAMA network open · 2024Article
- Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders.Frontiers in neural circuits · 2024Article
- Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.Current neuropharmacology · 2024Review
- Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders.International journal of molecular sciences · 2023Article
- Brain Neuroplasticity after Treatment with Antiseizure: A Review.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023Review
- Integrative systems biology characterizes immune-mediated neurodevelopmental changes in murine Zika virus microcephaly.iScience · 2023Article
- Glycolysis mediates neuron specific histone acetylation in valproic acid-induced human excitatory neuron differentiation.Frontiers in molecular neuroscience · 2023Article
- Induction of cerebellar cortical neurogenesis immediately following valproic acid exposure in ferret kits.Frontiers in neuroscience · 2023Article
- Focus on your locus with a massively parallel reporter assay.Journal of neurodevelopmental disorders · 2022Review
- Transcriptomic analysis in the striatum reveals the involvement of Nurr1 in the social behavior of prenatally valproic acid-exposed male mice.Translational psychiatry · 2022Article
- Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA), a widely used antiepileptic drug, is an inhibitor of histone deacetylases, which epigenetically modify cell proliferation/differentiation in developing tissues. A series of recent clinical studies in humans reported that VPA exposure in utero impaired histogenesis and the development of the central nervous system, leading to increased risks of congenital malformation and the impairment of higher brain functions in children. In the present study conducted in mice, we report that VPA exposure in utero (1) increases the amount of acetylated histone proteins, (2) alters the expression of G1-phase regulatory proteins, (3) inhibits the cell cycle exit of neural progenitor cells during the early stage of neocortical histogenesis, and (4) increases the production of projection neurons distributed in the superficial neocortical layers in embryonic brains. Together, our findings show that VPA exposure in utero alters proliferation/differentiation characteristics of neural progenitor cells and hence leads to the neocortical dysgenesis. SIGNIFICANCE STATEMENT: This study provides new insight into the mechanisms of how an altered in utero environment, such as drug exposure, affects the generation of neurons prenatally. The antiepileptic drug valproic acid (VPA) is a good target molecule as in utero exposure to VPA has been repeatedly reported to increase the risk of nervous system malformations and to impair higher brain functions in children. We show that VPA decreases the probability of differentiation of the neural progenitor cells (NPCs) in mice, resulting in an abnormally increased number of projection neurons in the superficial layers of the neocortex. Further, we suggest that histone deacetylase inhibition by VPA may be involved in the dysregulation of proliferation/differentiation characteristics of NPCs.
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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.