title: Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats.
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.
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, PR China.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Han
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000069450:Liraglutide; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP