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

Paula McClean, Victor A Gault, Patrick Harriott, Christian Holscher

Research output: Contribution to journalArticle

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 15 nmol in 5 mu l i c v. Liraglutide (P < 0005), Asp(7)GLP-1 (P < 0001), N-glyc-GLP-1 (P < 001), 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 oil 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 (C) 2009 Elsevier B V. All rights reserved
LanguageEnglish
Pages158-162
JournalEuropean Journal of Pharmacology
Volume630
Issue number1-3
DOIs
Publication statusPublished - Mar 2010

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Neuronal Plasticity
Glucagon-Like Peptide 1
Alzheimer Disease
Brain
Insulin
Type 2 Diabetes Mellitus
Proglucagon
Incretins
Viperidae
Synaptic Transmission
Hippocampus
Oils
Communication
Liraglutide
Hormones
Peptides
Injections
Enzymes

Cite this

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title = "Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: A link between diabetes and Alzheimer's disease",
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 15 nmol in 5 mu l i c v. Liraglutide (P < 0005), Asp(7)GLP-1 (P < 0001), N-glyc-GLP-1 (P < 001), 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 oil 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 (C) 2009 Elsevier B V. All rights reserved",
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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 A; Harriott, Patrick; Holscher, Christian.

In: European Journal of Pharmacology, Vol. 630, No. 1-3, 03.2010, p. 158-162.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: A link between diabetes and Alzheimer's disease

AU - McClean, Paula

AU - Gault, Victor A

AU - Harriott, Patrick

AU - Holscher, Christian

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N2 - 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 15 nmol in 5 mu l i c v. Liraglutide (P < 0005), Asp(7)GLP-1 (P < 0001), N-glyc-GLP-1 (P < 001), 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 oil 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 (C) 2009 Elsevier B V. All rights reserved

AB - 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 15 nmol in 5 mu l i c v. Liraglutide (P < 0005), Asp(7)GLP-1 (P < 0001), N-glyc-GLP-1 (P < 001), 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 oil 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 (C) 2009 Elsevier B V. All rights reserved

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M3 - Article

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T2 - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

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