Open AccessValproic acid enhances neurosphere formation in cultured rat embryonic cortical cells through TGFβ1 signaling
Author(s) -
Cui Qi,
Jiaqi Zhang,
Yuanyuan Wang,
Mingyan Lin,
Jun Gao,
Haiying Lu
Publication year - 2022
Publication title -
journal of biomedical research/journal of biomedical research
Language(s) - English
Resource type - Journals
eISSN - 2352-4685
pISSN - 1674-8301
DOI - 10.7555/jbr.36.20210109
Subject(s) - neurosphere , neural stem cell , embryonic stem cell , valproic acid , microbiology and biotechnology , chemistry , apoptosis , transforming growth factor , downregulation and upregulation , biology , stem cell , biochemistry , neuroscience , epilepsy , gene , adult stem cell
This study aimed to investigate the effect and mechanism of valproic acid (VPA) on the neurosphere formation in rat embryonic cortical cells. We used free-floating neurosphere formation as a model system to evaluate the VPA on the proliferation of neural stem cells (NSCs). We found a time- and dose-dependent increase in neurosphere formation and NSC proliferation after VPA treatment. Further RNA-seq analysis demonstrated that the upregulated TGFβ1 signaling might attribute to the effect of VPA on the neurosphere formation and NSC proliferation. Consistently, the neurosphere formation and NSC proliferation were blocked by the treatment with SB431542, an inhibitor of TGFβ1 receptor. Moreover, in a coculture system, NSCs treated with VPA significantly reduced the oxygen-glucose deprivation-induced neuronal apoptosis. Taken together, our results showed that VPA could enhance neurosphere formation and NSC proliferation by activating TGFβ1, which might be a novel therapeutic strategy for neurological disorders.