ArticleFrontiers in aging neuroscience2019
Valproic Acid Stimulates Hippocampal Neurogenesis
Article in Frontiers in aging neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A Multi-Ancestry GWAS Meta-Analysis Integrated with In-Depth Silico, Systems Biology, and Pharmacogenomics Approaches on Alzheimer's Disease Among 1,198,689 Subjects.Journal of molecular neuroscience : MN · 2025Pooled it
- Histone Deacetylase Inhibitors Improve Memory Function and Decrease Neuropathology in APP/PS1 Mice.Research square · 2026Article
- Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Beyond epilepsy: The expanding role of valproic acid in Alzheimer disease therapy - a review.The Journal of pharmacology and experimental therapeutics · 2025Review
- Modulation of the cognitive impairment associated with Alzheimer's disease by valproic acid: possible drug repurposing.Inflammopharmacology · 2025Article
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Lateral hypothalamic area high-frequency deep brain stimulation rescues memory decline in aged rat: behavioral, molecular, and electrophysiological study.Pflugers Archiv : European journal of physiology · 2025Article
- Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Inflammasomes in Alzheimer's Progression: Nrf2 as a Preventive Target.Antioxidants (Basel, Switzerland) · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson's Disease: Preliminary In Vivo Data.Brain sciences · 2024Article
- Classic Famous Prescription Kai-Xin-San Ameliorates Alzheimer's Disease via the Wnt/β-Catenin Signaling Pathway.Molecular neurobiology · 2024Article
- Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals.Heliyon · 2024Review
- Histone deacetylase inhibitors VPA and WT161 ameliorate the pathological features and cognitive impairments of the APP/PS1 Alzheimer's disease mouse model by regulating the expression of APP secretases.Alzheimer's research & therapy · 2024Article
- Neurotrophic Natural Products.Progress in the chemistry of organic natural products · 2024Article
- Host-gut microbiota derived secondary metabolite mediated regulation of Wnt/β-catenin pathway: a potential therapeutic axis in IBD and CRC.Frontiers in oncology · 2024Review
- Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway.BMC neuroscience · 2023Article
- Histone Modifications in Alzheimer's Disease.Genes · 2023Review
- Induction of cerebellar cortical neurogenesis immediately following valproic acid exposure in ferret kits.Frontiers in neuroscience · 2023Article
- Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury.Acta biochimica et biophysica Sinica · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by the deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) and massive loss of neuronal cells in the brain. Adult hippocampus continuously generates new neurons throughout life to shape brain function and impaired neurogenesis may contribute to a series of cognitive deterioration associated with AD. Enhancing endogenous neurogenesis represents a promising strategy that may ameliorate AD-associated cognitive defects. However, neurogenesis-enhancing approaches and underlying mechanisms are still not well studied. Here, using a mouse model of AD amyloid precursor protein (APP/PS1/Nestin-GFP triple transgenic mice, 3xTgAD), we examined the effects of 4 weeks of valproic acid (VPA) treatment on hippocampal neurogenesis in 2- and 6-month-old mice. VPA treatment promoted cell proliferation and increased the density of immature neurons in the dentate gyrus (DG) of the hippocampus of 3xTgAD mice. Consistent with enhanced neurogenesis, behavioral and morphological analysis showed that VPA treatment improved the learning and memory ability of 3xTgAD mice. Mechanistically, VPA treatment increased β-catenin levels, accumulated the inactive form of glycogen synthase kinase-3β (GSK-3β), and induced the expression of NeuroD1, a Wnt target gene involved in neurogenesis, suggesting the activation of the Wnt signaling pathway in the hippocampus of 3xTgAD mice. This study indicates that VPA stimulates neurogenesis in the adult hippocampus of AD mice model through the Wnt pathway, highlighting VPA as a potential therapeutic for treating AD and related diseases.
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Registered trials
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