Sodium valproate ameliorates memory impairment and reduces the elevated levels of apoptotic caspases in the hippocampus of diabetic mice.

Abstract

Learning and memory deficits appear in chronic diabetes and valproic acid has been proved to be beneficial in neurodegenerative diseases. Hence, the current study investigated the effectiveness of chronic valproate treatment for diabetes-induced memory impairment and increased levels of hippocampal apoptotic caspases. This study was conducted in adult male C57B15/J mice. Diabetes, which was induced by alloxan (150mg/kg; i.p.), was confirmed when fasting blood sugar (FBS) was > 200mg/dl. Sodium valproate (100mg/kg; i.p.) was administrated to the diabetic and non-diabetic groups, every 72h for 2months. Next, all groups were evaluated for memory performance using the radial maze and shuttle box. After FBS measurement, animals were killed and the hippocampus was extracted and prepared for ELISA to assess caspase levels. Diabetic animals had significantly high FBS and memory impairment 2months after the alloxan injection. Hippocampal levels of caspases 3, 6, and 8 were significantly higher in the diabetic group than in the control group. However, valproate treatment of diabetic animals significantly improved memory performance in both the radial maze and shuttle box and reduced the elevated levels of hippocampal apoptotic caspases, in comparison with diabetic animals. Chronic administration of valproate seems to have beneficial effects on diabetic neuropathy.