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 (150 mg/kg; i.p.), was confirmed when fasting blood sugar (FBS) was > 200 mg/dl. Sodium valproate (100 mg/kg; i.p.) was administrated to the diabetic and non-diabetic groups, every 72 h for 2 months. 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 2 months 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.
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This study was supported by Arak University of Medical Sciences (Funding Nos. 2655 and 2688).
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MS was responsible for the study concept and design. PZ, MG, BA, and SH performed the acquisition of animal data. PZ, MG, and MS contributed to the analysis and interpretation of findings. PZ, MG, and MS drafted and revised the manuscript for important intellectual content. All authors critically reviewed and revised content, and approved the final version for publication.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.
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The authors declare that they have no conflicts of interest.
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Parvin Zareie and Mahsa Gholami had the same cooperation in this work.
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Zareie, P., Gholami, M., Amirpour-najafabadi, B. et al. Sodium valproate ameliorates memory impairment and reduces the elevated levels of apoptotic caspases in the hippocampus of diabetic mice. Naunyn-Schmiedeberg's Arch Pharmacol 391, 1085–1092 (2018). https://doi.org/10.1007/s00210-018-1531-3
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DOI: https://doi.org/10.1007/s00210-018-1531-3