ArticleThe Journal of biological chemistry2015
Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 91 citations in OpenAlex.
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- The active metabolite of Epimedii Folium promotes hippocampal neurogenesis in APP/PS1 mice by alleviating mitochondrial dysfunction.Frontiers in pharmacology · 2025Article
- Bisphenol-F and Bisphenol-S (BPF and BPS) Impair the Stemness of Neural Stem Cells and Neuronal Fate Decision in the Hippocampus Leading to Cognitive Dysfunctions.Molecular neurobiology · 2024Article
- Adropin: A crucial regulator of cardiovascular health and metabolic balance.Metabolism open · 2024Review
- Curcumin Improves Neurogenesis in Alzheimer's Disease Mice via the Upregulation of Wnt/β-Catenin and BDNF.International journal of molecular sciences · 2024Article
- Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals.Heliyon · 2024Review
- Bisphenol-A (BPA) Impairs Hippocampal Neurogenesis via Inhibiting Regulation of the Ubiquitin Proteasomal System.Molecular neurobiology · 2023Article
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- Tetramethylpyrazine protects neural stem cells against sevoflurane-induced toxicity through Akt/GSK-3β pathway.Metabolic brain disease · 2022Article
- Molecular Insights to the Wnt Signaling During Alzheimer's Disorder: a Potential Target for Therapeutic Interventions.Journal of molecular neuroscience : MN · 2022Review
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- Neuroprotective activity of natural products isolated from Senecio graciliflorus DC against corticosterone-induced impairment in SH-SY5Y cells.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.BMC complementary medicine and therapies · 2021Article
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- 4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Effect of Lacosamide and Ethosuximide Chronic Treatment on Neural Precursor Cells and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice.Brain sciences · 2021Article
- Mitochondrial Protein Import Dysfunction in Pathogenesis of Neurodegenerative Diseases.Molecular neurobiology · 2021Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid β (Aβ) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aβ toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aβ-mediated suppression of neurogenic and Akt/Wnt/β-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·β-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·β-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3β. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·β-catenin signaling.
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