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Valproic Acid Inhibits Neurosphere Formation By Adult Subventricular Cells By A Lithium-Sensitive Mechanism, Q. Zhou, C. L. Dalgard, C. Wynder, M. L. Doughty

Uniformed Services University of the Health Sciences

The mood stabilizer valproic acid (VPA) decreases neural progenitor proliferation and promotes neurogenesis in the adult hippocampus. However, the effects of VPA on progenitor cells in the adult subventricular zone (SVZ) are not as well characterized. Here we report VPA blocks neurosphere formation and inhibits DNA synthesis in cultured NSCs from the SVZ of adult mice. Inhibition of DNA synthesis is associated with the up-regulation of the differentiation transcription factors Egr1 and Neurod1 and down-regulation of transcription factors associated with “stemness”. Co-treatment of VPA with the mood stabilizer lithium antagonizes the anti-proliferative effects of VPA on adult NSCs and abolishes …