Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats

Cai, H.-Y. and Hölscher, Christian and Yue, X.-H. and Zhang, S.-X. and Wang, X.-H. and Qiao, F. and Yang, W. and Qi, J.-S. (2014) Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats. Neuroscience, 277. pp. 6-13. ISSN 0306-4522

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Abstract

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by cognitive impairment, but effective strategies against AD are currently not available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, the neuroprotective effects of lixisenatide in the brain remain to be clarified. In the present study, we report for the first time the effects of lixisenatide on the amyloid β (Aβ) protein-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms. We found that: (1) bilateral intrahippocampal injection of Aβ25-35 resulted in a significant decline in spatial learning and memory of rats, as well as a suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide treatment effectively prevented the Aβ25-35-induced impairments; (3) lixisenatide inhibited the Aβ25-35 injection-induced activation of glycogen synthase kinase 3β (GSK3β), with a significant increase in the phosphorylation of ser9 and a significant decrease in the phosphorylation of Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt-GSK3β pathway, can prevent Aβ-related impairments in synaptic plasticity and spatial memory of rats, suggesting that lixisenatide may be a novel and effective treatment for AD.

Item Type: Journal Article
Journal or Publication Title: Neuroscience
Additional Information: Copyright © 2014. Published by Elsevier Ltd.
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2800
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 69046
Deposited By: ep_importer_pure
Deposited On: 02 Apr 2014 08:34
Refereed?: Yes
Published?: Published
Last Modified: 07 Jan 2020 04:01
URI: https://eprints.lancs.ac.uk/id/eprint/69046

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