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Research Paper|Volume 12, Issue 14|pp 14205—14218

Lowered levels of nicotinic acetylcholine receptors and elevated apoptosis in the hippocampus of brains from patients with type 2 diabetes mellitus and db/db mice

Yi Xu1,2, Kun Cao2, Bing Guo3, Jie Xiang1,2, Yang-Ting Dong2,4, Xiao-Lan Qi2,4, Wen-Feng Yu2,4, Yan Xiao2,4, Zhi-Zhong Guan1,2,4
  • 1Departments of Pathology at Guizhou Medical University and the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P. R. of China
  • 2Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University of the Ministry of Education, Guiyang 550004, P. R. of China
  • 3Department of Pathophysiology, Guizhou Medical University, Guiyang 550004, P. R. of China
  • 4Provincial Key Laboratory of Medical Molecular Biology, Guiyang 550004, P. R. of China
Received: January 16, 2020Accepted: May 25, 2020Published: July 23, 2020
https://doi.org/10.18632/aging.103435

Copyright: © 2020 Xu 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.

Abstract

Cognitive impairment caused by diabetes has been gradually recognized. Generally, nicotinic acetylcholine receptors (nAChRs) play an important role in the pathogenesis in dementia disorders including Alzheimer's disease (AD). However, the expression of nAChRs in the brains of type 2 diabetes mellitus (T2DM) is unexplored. This study explored the alterations of nAChRs in the postmortem brains of patients with T2DM and brains of db/db mice. Morris water maze test was used to appraise the ability of spatial learning and memory; Western blotting and RT-qPCR were performed to determine the expressions of target protein and mRNA, respectively; TUNEL was used to detect the apoptosis of neurons. We found that the protein levels of nAChR α7 and α4 subunits were significantly decreased and the apoptosis rates in neurons elevated in the hippocampus of T2DM patients and db/db mice as comparison to controls. Furthermore, the db/db mice exhibited the impaired cognition, the elevated level of pro-apoptotic protein and the reduced level of anti-apoptotic and synaptic proteins. This study shows the lowered level of nAChR α7 and α4 subunits and the elevated apoptosis in the hippocampus of T2DM patients and db/db mice, which might help explain the impaired cognition in T2DM.