Diabetic cognitive dysfunction has gained widespread attention for its deleterious impact on individuals with diabetes. However, few clinical interventions are available to prevent the disorder. The glucagon-like peptide-1 analog liraglutide exerts neuroprotective effects in several models of neurodegenerative diseases. We investigated the effect of liraglutide pretreatment on diabetes-induced cognitive decline and explored the underlying mechanisms in vivo and in vitro. Liraglutide pretreatment prevented diabetes-induced cognitive impairment as assessed by the Morris Water Maze test, and alleviated neuronal injuries and ultrastructural damage to synapses in the hippocampal CA1 region. Furthermore, liraglutide promoted autophagy as indicated by enhanced expression of the autophagy markers Microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin 1, decreased expression of p62, and increased formation of autophagic vacuoles and LC3-II aggregates. In vitro, liraglutide treatment elevated phosphorylated (p)-AMP-activated protein kinase (AMPK) levels and reduced p-mammalian target of rapamycin (p-mTOR) expression. Additionally, the AMPK inhibitor Compound C exhibited an inhibitory effect on liraglutide-induced increased LC3-II expression and p62 degradation. Liraglutide exhibits neuroprotective effects against diabetes-induced hippocampal neuronal injuries and cognitive impairment by promoting autophagy via the AMPK/mTOR pathway. (C) 2018 Published by Elsevier Ltd.
[1]Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Endocrinol, 3 East Qingchun Rd, Hangzhou 310016, Zhejiang, Peoples R China.
[2]Tongji Univ, Shanghai Peoples Hosp 10, Dept Endocrinol & Metab, Sch Med, Shanghai, Peoples R China.
[3]Fudan Univ, Shanghai Inst Cardiovasc Dis, Zhongshan Hosp, Shanghai, Peoples R China.
(8.0+极速模式)