Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats

Han, Wei-Na and Hölscher, Christian and Yuan, Li and Yang, Wei and Wang, Xiao-Hui and Wu, Mei-Na and Qi, Jin-Shun (2013) Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. Neurobiology of Aging, 34 (2). pp. 576-588. ISSN 0197-4580

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Abstract

Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most likely linked to an impairment of insulin signaling in the brain. Liraglutide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin signaling and shows neuroprotective properties. In the present study, we analyzed the effects of liraglutide on the impairment of learning and memory formation induced by amyloid-β protein (Aβ), and the probable underlying electrophysiological and molecular mechanisms. We found that (1) bilateral intrahippocampal injection of Aβ(25-35) resulted in a significant decline of spatial learning and memory of rats in water maze tests, together with a serious depression of in vivo hippocampal late-phase long-term potentiation (L-LTP) in CA1 region of rats; (2) pretreatment with liraglutide effectively and dose-dependently protected against the Aβ(25-35)-induced impairment of spatial memory and deficit of L-LTP; (3) liraglutide injection also activated cAMP signal pathway in the brain, with a nearly doubled increase in the cAMP contents compared with control. These results strongly suggest that upregulation of GLP-1 signaling in the brain, such as application of liraglutide, may be a novel and promising strategy to ameliorate the learning and memory impairment seen in AD.

Item Type:
Journal Article
Journal or Publication Title:
Neurobiology of Aging
Additional Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1302
Subjects:
ID Code:
69059
Deposited By:
Deposited On:
04 Apr 2014 12:55
Refereed?:
Yes
Published?:
Published
Last Modified:
20 Oct 2020 02:52