Lixisenatide attenuates the detrimental effects of amyloid β protein on spatial working memory and hippocampal neurons in rats

Cai, Hong-Yan and Wang, Zhao-Jun and Holscher, Christian and Yuan, Li and Zhang, Jun and Sun, Peng and Li, Jing and Yang, Wei and Wu, Mei-Na and Qi, Jin-Shun (2017) Lixisenatide attenuates the detrimental effects of amyloid β protein on spatial working memory and hippocampal neurons in rats. Behavioural Brain Research, 318. pp. 28-35. ISSN 0166-4328

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Abstract

Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer’s disease (AD), which is most likely linked to impairments of insulin signaling in the brain. Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, facilitates insulin signaling and has neuroprotective properties. We previously reported the protective effects of lixisenatide on memory formation and synaptic plasticity. Here, we describe additional key neuroprotective properties of lixisenatide and its possible molecular and cellular mechanisms against AD-related impairments in rats. The results show that lixisenatide effectively alleviated amyloid β protein (Aβ) 25-35-induced working memory impairment, reversed Aβ25-35-triggered cytotoxicity on hippocampal cell cultures, and prevented against Aβ25-35-induced suppression of the Akt-MEK1/2 signaling pathway. Lixisenatide also reduced the Aβ25-35 acute application induced intracellular calcium overload, which was abolished by U0126, a specific MEK1/2 inhibitor. These results further confirmed the neuroprotective and cytoprotective action of lixisenatide against Aβ-induced impairments, suggesting that the protective effects of lixisenatide may involve the activation of the Akt-MEK1/2 signaling pathway and the regulation of intracellular calcium homeostasis.

Item Type: Journal Article
Journal or Publication Title: Behavioural Brain Research
Additional Information: This is the author’s version of a work that was accepted for publication in Behavioural Brain Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Behavioural Brain Research , 318, 2016 DOI: 10.1016/j.bbr.2016.10.033
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2800/2802
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 82575
Deposited By: ep_importer_pure
Deposited On: 03 Nov 2016 14:24
Refereed?: Yes
Published?: Published
Last Modified: 17 Feb 2020 03:18
URI: https://eprints.lancs.ac.uk/id/eprint/82575

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