Research Paper Volume 13, Issue 3 pp 4590—4604
Decreased miR-132 plays a crucial role in diabetic encephalopathy by regulating the GSK-3β/Tau pathway
- 1 Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, China
- 2 Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang 050000, China
- 3 Department of Endocrinology, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China
- 4 School of Basic Medicine, The Fourth Military Medical University, Xi'an 710032, China
- 5 Department of General Practice, Xingtai People’s Hospital, Xingtai 054000, China
- 6 Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang 075000, China
- 7 Hebei International Joint Research Center for Brain Science, Shijiazhuang 075000, China
Received: July 27, 2020 Accepted: November 10, 2020 Published: December 27, 2020https://doi.org/10.18632/aging.202418
How to Cite
Copyright: © 2020 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Diabetic encephalopathy (DE) is a global concern and Gordian knot worldwide. miRNA-132 (miR-132) is a class of negative gene regulators that promote diabetic pathologic mechanisms and its complications. However, the molecular mechanisms of miR-132 in DE are elusive, thus an alternative therapeutic strategy is urgently in demand. The present study explored the protective effect and the underlying mechanism of miR-132 on DE via the GSK-β/Tau signaling pathway. Experimentally, a type 2 DM rat model was developed by incorporating a high-fat diet and streptozotocin injection. Further, the DE model was screened via the Morris Water Maze test. Primary hippocampal neurons and HT-22 cells were used for in vitro analysis. We found that hyperglycemia exacerbates cognitive impairment in T2DM rats. When we isolated the primary hippocampus neurons, the expression of miR-132 RNA was low in both the DE hippocampus and primary neurons. GSK-3β and Tau 404 were highly expressed in injured HT-22 cells and diabetic hippocampal tissues. miR-132 downregulated the expression of GSK-3β. Besides, a binding and colocalized relationship between GSK3β and Tau was also reported. These findings suggest that miR-132 exerts protective effects from DE injury by repressing GSK-3β expression and alleviating Tau hyperphosphorylation in HT-22 cells and hippocampus tissues.