Valproic Acid Promotes the Differentiation of Satellite Glial Cells into Neurons via the pH-Dependent Pathway

Valproic acid (VPA) is a widely prescribed antiepileptic agent whose teratogenic potential has been recognized. In recent years, VPA has been shown to promote neuronal regeneration; however, the exact molecular mechanisms are not fully understood. This study elucidates the pH-dependent pathway throu...

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Main Authors: Dongyan Wang, Wenrun Kang, Jinhui Zhang, Jianwei Xu, Ruyi Wang, Xiangdan Xiao, Chao Wei, Wenfeng Yu, Junhou Lu
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/7/986
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Summary:Valproic acid (VPA) is a widely prescribed antiepileptic agent whose teratogenic potential has been recognized. In recent years, VPA has been shown to promote neuronal regeneration; however, the exact molecular mechanisms are not fully understood. This study elucidates the pH-dependent pathway through which VPA promotes the differentiation of satellite glial cells (SGCs) into neurons. We observed sustained intracellular pH elevation during the VPA-induced neural differentiation of SGCs, and the modulation of intracellular pH was shown to influence this differentiation process. Then, we found that VPA regulates intracellular pH through NHE1 (sodium–hydrogen exchanger 1), and that the pharmacological inhibition of NHE1 not only attenuated intracellular pH elevation but also substantially impaired VPA-induced neuronal differentiation. Finally, our results showed that the elevated intracellular pH promoted the neuronal differentiation of SGCs by activating β-catenin signaling. These findings provide novel insights into the mechanisms of VPA-induced neurogenesis, advancing our understanding of its pharmacological profile and informing its potential therapeutic application in neuronal regeneration strategies.
ISSN:2218-273X