Format

Send to

Choose Destination
Neuropharmacology. 2018 Mar 15;131:316-325. doi: 10.1016/j.neuropharm.2018.01.001. Epub 2018 Jan 3.

Liraglutide ameliorates cognitive decline by promoting autophagy via the AMP-activated protein kinase/mammalian target of rapamycin pathway in a streptozotocin-induced mouse model of diabetes.

Author information

1
Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
2
Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
3
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
4
Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zjq8866@zju.edu.cn.

Abstract

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.

KEYWORDS:

Autophagy; Cognitive decline; Diabetes; Liraglutide; Neuronal apoptosis

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center