Firat University, School of Medicine, Department of Psychiatry, Elazig, Turkey.
Int Rev Psychiatry. 2009;21(4):410-3. doi: 10.1080/09540260902962206.
Valproate is an anticonvulsant drug but also a mood stabilizer commonly used to treat bipolar disorder. It has a structure of short-chain fatty acid and is becoming a first line treatment for bipolar disorder. The effect mechanism of the vaproate has not been completely established but it has been suggested that alterations in gene expression may be involved in chronic treatment. On the other hand, a growing body of evidence emphasizes that valproate has neuroprotective and neurotrophic actions. Neuroimaging studies that examine neurochemistry in the living brain provide further support for the hypothesis that bipolar disorder is related to changes in neuronal viability and function. In cellular view of point, it was showed that valproate protected rat cerebral cortical and cerebellar granule cells from glutamate-related excitotoxicity, and apoptotic death of the endoplasmic reticulum in C6 glioma cells and PC 12 cells. At the genetic level, growing data suggest that the long-term treatment of mood disorders may involve the regulation of signalling pathways and gene expression in critical neuronal circuits. It has been shown that lithium and valproate produce some changes in basal and stimulated DNA binding to activator protein 1 (AP-1) transcription factors, considering that strategic changes in gene expression in critical neuronal circuits may be important in the treatment of a variety of psychiatric disorders. So, a growing body of evidence establishes its neuroprotective and neurotrophic actions in bipolar disorder.
丙戊酸盐是一种抗惊厥药物，但也是一种常用的情绪稳定剂，用于治疗双相情感障碍。它具有短链脂肪酸的结构，已成为双相情感障碍的一线治疗药物。丙戊酸盐的作用机制尚未完全确定，但有研究表明，基因表达的改变可能与慢性治疗有关。另一方面，越来越多的证据强调丙戊酸盐具有神经保护和神经营养作用。研究活体大脑神经化学的神经影像学研究为双相情感障碍与神经元存活和功能改变有关的假设提供了进一步的支持。从细胞角度来看，丙戊酸盐可以保护大鼠皮质和小脑颗粒细胞免受谷氨酸相关的兴奋性毒性和 C6 神经胶质瘤细胞和 PC12 细胞内质网的凋亡性死亡。在基因水平上，越来越多的证据表明，情绪障碍的长期治疗可能涉及关键神经元回路中信号通路和基因表达的调节。已经表明，锂和丙戊酸盐会导致基础和刺激的激活蛋白 1（AP-1）转录因子结合的 DNA 发生一些变化，考虑到关键神经元回路中基因表达的策略性改变可能对各种精神疾病的治疗很重要。因此，越来越多的证据表明丙戊酸盐在双相情感障碍中具有神经保护和神经营养作用。
