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

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Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. / Han, Wei-Na; Hölscher, Christian; Yuan, Li et al.

In: Neurobiology of Aging, Vol. 34, No. 2, 02.2013, p. 576-588.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Han, W-N, Hölscher, C, Yuan, L, Yang, W, Wang, X-H, Wu, M-N & Qi, J-S 2013, 'Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats', Neurobiology of Aging, vol. 34, no. 2, pp. 576-588. https://doi.org/10.1016/j.neurobiolaging.2012.04.009

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Vancouver

Han W-N, Hölscher C, Yuan L, Yang W, Wang X-H, Wu M-N et al. Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. Neurobiology of Aging. 2013 Feb;34(2):576-588. doi: 10.1016/j.neurobiolaging.2012.04.009

Author

Han, Wei-Na ; Hölscher, Christian ; Yuan, Li et al. / Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 2. pp. 576-588.

Bibtex

@article{ca2a31677049439994c8dad611c21ed7,
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.",
keywords = "Amyloid beta-Peptides, Animals, Cyclic AMP, Excitatory Postsynaptic Potentials, Glucagon-Like Peptide 1, Hippocampus, Long-Term Potentiation, Male, Maze Learning, Memory, Peptide Fragments, Rats, Rats, Sprague-Dawley",
author = "Wei-Na Han and Christian H{\"o}lscher and Li Yuan and Wei Yang and Xiao-Hui Wang and Mei-Na Wu and Jin-Shun Qi",
note = "Copyright {\textcopyright} 2013 Elsevier Inc. All rights reserved.",
year = "2013",
month = feb,
doi = "10.1016/j.neurobiolaging.2012.04.009",
language = "English",
volume = "34",
pages = "576--588",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "2",

}

RIS

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 -