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Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: A link between diabetes and Alzheimer's disease.

McClean, Paula, Gault, Victor, Harriott, Patrick and Holscher, Christian (2009) Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: A link between diabetes and Alzheimer's disease. European journal of pharmacology, epub . [Journal article]

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URL: http://www.ncbi.nlm.nih.gov/pubmed/20035739?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

DOI: 2003573

Abstract

Type 2 diabetes has been identified as a risk factor for patients with Alzheimer's disease. Insulin signalling is often impaired in Alzheimer's disease, contributing to the neurodegenerative process. One potential strategy to help prevent this is the normalisation of insulin signalling in the brain. Therefore, the present study was designed to test the effects of novel enzyme-resistant analogues of the insulin-releasing incretin hormone, glucagon-like peptide 1 (GLP-1). The effects of Liraglutide (Victoza) and other novel GLP-1 analogues were tested on synaptic plasticity (LTP) in area CA1 of the hippocampus. At a dose of 15nmol in 5microl i.c.v., Liraglutide (P<0.005), Asp(7)GLP-1 (P<0.001), N-glyc-GLP-1 (P<0.01), and Pro(9)GLP-1 (P<0.001). In contrast, the GLP-1 receptor antagonist exendin(9-39)amide impaired LTP (P<0.001). Co-injection of exendin(9-39) and Liraglutide showed no effect on LTP. These results clearly demonstrate that Liraglutide and other GLP-1 analogues elicit effects on neurotransmission in the brain. Furthermore, GLP-1 peptides are not only effective in modulating insulin-release and achieving glycaemic control in type 2 diabetes, but are also effective in modulating synaptic plasticity. These findings are consistent with our previous observations that the novel analogue (Val(8))GLP-1 enhances LTP and reverses the impairments of LTP induced by beta-amyoid fragments. Therefore, the drug effects seen here could potentially ameliorate the impairments in neuronal communication and cognitive processes observed in Alzheimer's disease.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Stratified Medicine
Biomedical Sciences Research Institute > Genomic Medicine > Neuroscience & Neurodegenerative Diseases
Biomedical Sciences Research Institute > Diabetes
ID Code:11226
Deposited By: Dr Christian Holscher
Deposited On:04 Feb 2010 09:41
Last Modified:15 Oct 2013 15:36

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