Abstract
Diabetes mellitus (DM) is associated with the increased risk of the central nervous system complications as cerebrovascular disease, impaired cognition, dementia and neurodegeneration. Curcumin is a polyphenol with anti-oxidant, anti-inflammatory, anti-hyperlipidemic, and anti-cancer effects. Therefore, the present study was aimed to focus on the mechanistic insights of diabetes-induced hippocampal neurodegeneration in addition to shedding the light on the modulatory effect of curcumin. Twenty-eight male Wistar rats were randomly divided into four groups. Type I DM was induced by a single intra-peritoneal injection of streptozotocin (STZ) (65 mg/kg b.w.). Curcumin (100 mg/kg b.w.) was given to the diabetic group after the induction and for eight weeks. Hippocampal glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF-4), Bcl2 and choline acetyl transferase (ChAT) genes expression were assessed. Heat shock protein 70 (HSP70), Bcl-2-Associated X protein (Bax), Interferon-γ (INF-γ) and CCAAT-enhancer-binding protein homologous protein (CHOP) levels in the hippocampus were immunoassayed, in addition to the assessment of glycemic and redox status. Curcumin significantly improved blood glucose level, redox status, cellular stress, and decreased INF-γ and Bax levels, down-regulated GRP78 and ATF-4 expression, meanwhile, up-regulated Bcl2 and ChAT expression in hippocampus. Histological findings proved the biochemical and molecular findings. Our results support curcumin as a potential neuro-protective agent against diabetes induced hippocampal neurodegeneration.
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Acknowledgments
The authors would like to thank Dr./ Safwat M., (Nagoya City University) for providing anti-ChAT antibodies, helping in image analysis and for his helpful discussion. The authors are greatly appreciating the assistance provided by the technicians in Biochemistry, Histology departments and the central laboratory Faculty of Medicine, Tanta University, Egypt for the technical assistance.
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All the named authors participated sufficiently in this research work according to the specialty and expert of each one as follows: Walaa A. Keshk and Doaa H Zineldeen designed the research protocol, assay the biochemical parameters, conducted the statistical analysis, presented the results as tables or figures, wrote and revised the manuscript. Walaa S. Elseady and Naglaa I. Sarhan conducted the histological and immunohistochemical examination. All authors reviewed and edited the manuscript and approved its final version.
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Keshk, W.A., Elseady, W.S., Sarhan, N.I. et al. Curcumin attenuates cytoplasmic/endoplasmic reticulum stress, apoptosis and cholinergic dysfunction in diabetic rat hippocampus. Metab Brain Dis 35, 637–647 (2020). https://doi.org/10.1007/s11011-020-00551-0
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DOI: https://doi.org/10.1007/s11011-020-00551-0