Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis.

Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis. J Zhejiang Univ Sci B. 2019 Mar.;20(3):253-263 Authors: Pannangrong W, Sirichoat A, Wongsiri T, Wigmore P, Welbat JU Abstract Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. ...
Source: J Zhejiang Univ Sci ... - Category: Science Authors: Tags: J Zhejiang Univ Sci B Source Type: research