Acute valproate exposure affects proneural factor expression by increasing FOXO3 in the hippocampus of juvenile mice with a sex-based difference.

Eun Hye Jang, Soon Ae Kim

Neuroscience letters 2023 May 29

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Valproic acid (VPA), an anticonvulsant and mood stabilizer, may affect Notch signaling and mitochondrial function. In a previous study, acute VPA exposure induced increased expression of FOXO3, a transcription factor that shares common targets with pro-neuronal ASCL1. In this study, intraperitoneal acute VPA (400 mg/kg) administration in 4-week-old mice increased and decreased FOXO3 and ASCL1 expression, respectively, in the hippocampus, associated with sex-based differences. Treatment of Foxo3 siRNA increased the mRNA expression levels of Ascl1, Ngn2, Hes6, and Notch1 in PC12 cells. Furthermore, VPA exposure induced significant expression changes of mitochondria-related genes, including COX4 and SIRT1, in hippocampal tissues, associated with sex-based differences. This study suggests that acute VPA exposure differently affects proneural gene expression via FOXO3 induction in the hippocampus based on sex. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Eun Hye Jang, Soon Ae Kim. Acute valproate exposure affects proneural factor expression by increasing FOXO3 in the hippocampus of juvenile mice with a sex-based difference. Neuroscience letters. 2023 May 29;806:137226