Qi Cui, Zhang Jiaqi, Wang Yuanyuan, Lin Mingyan, Gao Jun, Lu Haiying
Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Department of Rehabilitation Medicine, Jiangsu Shengze Hospital affiliated to Nanjing Medical University, Suzhou, Jiangsu 215228,China.
J Biomed Res. 2022 Feb 15;36(2):127-140. doi: 10.7555/JBR.36.20210109.
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.
本研究旨在探讨丙戊酸（VPA）对大鼠胚胎皮质细胞神经球形成的影响及其机制。我们采用悬浮神经球形成作为模型系统来评估VPA对神经干细胞（NSCs）增殖的作用。我们发现VPA处理后神经球形成和NSCs增殖呈时间和剂量依赖性增加。进一步的RNA测序分析表明，上调的TGFβ1信号可能是VPA对神经球形成和NSCs增殖产生影响的原因。同样，用TGFβ1受体抑制剂SB431542处理可阻断神经球形成和NSCs增殖。此外，在共培养系统中，用VPA处理的NSCs显著减少了氧-葡萄糖剥夺诱导的神经元凋亡。综上所述，我们的结果表明VPA可通过激活TGFβ1增强神经球形成和NSCs增殖，这可能是一种治疗神经系统疾病的新策略。
