Open AccessAutophagy Activation is Associated with Neuroprotection in Diabetes-associated Cognitive Decline
Author(s) -
Yanqing Wu,
Libing Ye,
Yuan Yuan,
Ting Jiang,
Xin Guo,
Zhouguang Wang,
Ke Xu,
Zeping Xu,
Yanlong Liu,
Xingfeng Zhong,
Junmin Ye,
Hongyu Zhang,
Xiaokun Li,
Jian Xiao
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2018.1024
Subject(s) - autophagy , neuroprotection , hippocampus , dentate gyrus , cognitive decline , neuroscience , prefrontal cortex , atg5 , endocrinology , apoptosis , medicine , microbiology and biotechnology , biology , cognition , dementia , disease , biochemistry
Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of dysfunctional organelles and aggregated proteins. It has a neuroprotective role on neurodegenerative diseases. Here, we hypothesized that autophagy may also have a neuroprotective role in diabetes-associated cognitive decline (DACD). In current study, we found that db/db mice display cognitive decline with inferior learning and memory function. The accumulation of β-amyloid 1-42 (Aβ 1-42 ), which is a characteristic of Alzheimer's disease (AD), was markedly higher in the prefrontal cortex (PFC), cornu ammon1 (CA1), and dentate gyrus (DG) areas of the hippocampus in db/db mice. Moreover, BDNF and microtubule associated protein 2 (MAP2) levels were lower in the hippocampus of db/db mice. However, there was no noticeable differences in the level of apoptosis in the hippocampus between control (CON) mice and db/db mice. Markers of autophagy in the hippocampus were elevated in db/db mice. The expression levels of ATG5, ATG7, and LC3B were higher, and the level of P62 was lower. An autophagy inhibitor, 3-MA, and ATG7 siRNA significantly reversed the activation of autophagy in vitro , which was accompanied with a higher level of apoptosis. Taken together, our current study suggests that diabetes is associated with cognitive decline, and activation of autophagy has a neuroprotective role in DACD.