Exenatide alleviates mitochondrial dysfunction and cognitive impairment in the 5×FAD mouse model of Alzheimer's disease.

Abstract:

:The role of mitochondrial dysfunction has been well-documented in Alzheimer's disease (AD). Glucagon-like peptide 1 (GLP-1) receptor agonists are being utilized as neuroprotectants in the treatment of various neurological disorders, including AD. We conducted this study to explore the effects of exenatide (a GLP-1 receptor agonist) on β-amyloid plaque (Aβ)-induced cognitive impairment and mitochondrial dysfunction in 5xFAD transgenic mice. Spatial memory test showed that exenatide administration (100 μg/kg twice per day) prevented cognitive decline after 16 weeks of treatment. Aβ1-42 deposition and synapse damage in the hippocampus was significantly alleviated. Furthermore, exenatide treatment can improve mitochondrial morphology, relieve oxidative damage, correct mitochondrial energy crisis, and normalize mitochondrial dynamics. These findings suggest that exenatide, which has already been applied in clinical medicine, may be a promising agent for AD therapy via mitochondrial protection.

journal_name

Behav Brain Res

authors

An J,Zhou Y,Zhang M,Xie Y,Ke S,Liu L,Pan X,Chen Z

doi

10.1016/j.bbr.2019.111932

subject

Has Abstract

pub_date

2019-09-16 00:00:00

pages

111932

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(19)30242-6

journal_volume

370

pub_type

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