Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats
AU - Han, Wei-Na
AU - Hölscher, Christian
AU - Yuan, Li
AU - Yang, Wei
AU - Wang, Xiao-Hui
AU - Wu, Mei-Na
AU - Qi, Jin-Shun
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Amyloid beta-Peptides
KW - Animals
KW - Cyclic AMP
KW - Excitatory Postsynaptic Potentials
KW - Glucagon-Like Peptide 1
KW - Hippocampus
KW - Long-Term Potentiation
KW - Male
KW - Maze Learning
KW - Memory
KW - Peptide Fragments
KW - Rats
KW - Rats, Sprague-Dawley
U2 - 10.1016/j.neurobiolaging.2012.04.009
DO - 10.1016/j.neurobiolaging.2012.04.009
M3 - Journal article
C2 - 22592020
VL - 34
SP - 576
EP - 588
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 2
ER -