Document Detail


Glucagon-like peptide-1 cleavage product GLP-1(9-36) amide rescues synaptic plasticity and memory deficits in Alzheimer's disease model mice.
MedLine Citation:
PMID:  23035082     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucagon-like peptide-1 (GLP-1) is an endogenous intestinal peptide that enhances glucose-stimulated insulin secretion. Its natural cleavage product GLP-1(9-36)(amide) possesses distinct properties and does not affect insulin secretion. Here we report that pretreatment of hippocampal slices with GLP-1(9-36)(amide) prevented impaired long-term potentiation (LTP) and enhanced long-term depression induced by exogenous amyloid β peptide Aβ((1-42)). Similarly, hippocampal LTP impairments in amyloid precursor protein/presenilin 1 (APP/PS1) mutant mice that model Alzheimer's disease (AD) were prevented by GLP-1(9-36)(amide). In addition, treatment of APP/PS1 mice with GLP-1(9-36)(amide) at an age at which they display impaired spatial and contextual fear memory resulted in a reversal of their memory defects. At the molecular level, GLP-1(9-36)(amide) reduced elevated levels of mitochondrial-derived reactive oxygen species and restored dysregulated Akt-glycogen synthase kinase-3β signaling in the hippocampus of APP/PS1 mice. Our findings suggest that GLP-1(9-36)(amide) treatment may have therapeutic potential for AD and other diseases associated with cognitive dysfunction.
Authors:
Tao Ma; Xueliang Du; Joseph E Pick; Guangzhi Sui; Michael Brownlee; Eric Klann
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13701-8     Citation Subset:  IM    
Affiliation:
Center for Neural Science, New York University, New York, New York 10003, USA.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / drug therapy*,  genetics,  physiopathology,  psychology
Amyloid beta-Peptides / genetics,  pharmacology
Animals
Antioxidants / pharmacology,  therapeutic use*
Association Learning / drug effects
CA3 Region, Hippocampal / drug effects,  metabolism
Disease Models, Animal
Drug Evaluation, Preclinical
Excitatory Postsynaptic Potentials / drug effects,  physiology
Fear
Female
Glucagon-Like Peptide 1 / analogs & derivatives*,  pharmacology,  therapeutic use
Glycogen Synthase Kinase 3 / physiology
Male
Memory Disorders / drug therapy*,  physiopathology
Mice
Mice, Transgenic
Mitochondria / drug effects,  metabolism
Neuronal Plasticity / drug effects*
Nootropic Agents / pharmacology,  therapeutic use*
Organophosphorus Compounds / pharmacology
Peptide Fragments / pharmacology
Peptides / pharmacology,  therapeutic use*
Presenilin-1 / genetics
Proto-Oncogene Proteins c-akt / physiology
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Ubiquinone / analogs & derivatives,  pharmacology
Grant Support
ID/Acronym/Agency:
NS034007/NS/NINDS NIH HHS; NS047834/NS/NINDS NIH HHS; R01 NS034007/NS/NINDS NIH HHS; R01 NS047384/NS/NINDS NIH HHS; R21 NS078718/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Antioxidants; 0/Nootropic Agents; 0/Organophosphorus Compounds; 0/Peptide Fragments; 0/Peptides; 0/Presenilin-1; 0/Reactive Oxygen Species; 0/amyloid beta-protein (1-42); 0/glucagon-like peptide-1 (9-36)-amide; 0/mitoquinone; 1339-63-5/Ubiquinone; 89750-14-1/Glucagon-Like Peptide 1; EC 2.7.11.1/Akt1 protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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