Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction

Neuropeptides
Qiong XiangXian-Hui Li

Abstract

Several previous studies have indicated that diabetic have higher risk of suffering from Alzheimer's disease, which severely induced cognitive dysfunction. However, the underlying molecular mechanism and more details on the cognitive deficits induced by hyperglycemia have not been elucidated. Here in our present study, on the basis of Goto-Kakizaki (GK) rats and streptozotocin (STZ)-induced diabetic model, we detected the variation of dendritic spine density in hippocampus as well as the differential expression of some important signal transduction molecules that were of relevance in learning and memory function. We found that the magnitude of escape latency time was significantly increased in such diabetic animals; the phosphorylated Akt/CREB; SYP and BDNF as well as other downstream molecules in hippocampus neurons were also downregulated in both diabetic groups compared to the normal groups. Thus, all of these data indicate the obstacle of neuronal pathology and the Akt/CREB signaling pathway caused by hyperglycemia that may suppress cognitive behavior, which may provide a novel way for the prevention of diabetic encephalopathy and the cognitive deficits of Alzheimer's disease.

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Citations

Aug 16, 2016·Frontiers in Neuroendocrinology·Caterina PalleriaEmilio Russo
Mar 18, 2017·Journal of Agricultural and Food Chemistry·Jong Min KimHo Jin Heo
Nov 21, 2018·Synapse·Alejandra Aketzalli Flores-GómezGonzalo Flores
May 3, 2019·Journal of Neuroscience Research·Ana Francisca SoaresJoão M N Duarte
May 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Firas H BazzariHanan S El-Abhar
Oct 24, 2019·Journal of Alzheimer's Disease : JAD·Keren NitzanHanna Rosenmann
Apr 14, 2020·Cell Proliferation·Xiao Han ZouRan Ji Cui
Feb 8, 2019·Current Medicinal Chemistry·Jiyin ZhouGuisheng Qian
Jun 26, 2018·Frontiers in Cellular Neuroscience·Leonid M YermakovKeiichiro Susuki
Dec 11, 2019·Drug Development Research·Kavya JashKiran Kalia

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