Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice

Simon Gengler, Paula L. McClean, Ruth McCurtin, Victor Gault, Christian Holscher

Research output: Contribution to journalArticle

Abstract

Diabetes is a risk factor for Alzheimer's disease. We tested the effects of Val(8) GLP-1, an enzyme-resistant analogue of the incretin hormone glucagon-like peptide 1 originally developed to treat diabetes in a mouse model of Alzheimer's disease that expresses mutated amyloid precursor protein (APP) and presenilin-1. We tested long term potentiation (LTP) of synaptic plasticity, inflammation response, and plaque formation. Val(8) GLP-1 crosses the blood-brain barrier when administered via intraperitoneal injection. Val(8) GLP-1 protected LTP in 9- and 18-month-old Alzheimer's disease mice when given for 3 weeks at 25 nmol/kg intraperitoneally. LTP was also enhanced in 18-month-old wild type mice, indicating that Val(8) GLP-1 also ameliorates age-related synaptic degenerative processes. Paired-pulse facilitation was also enhanced. The number of beta-amyloid plaques and microglia activation in the cortex increased with age but was not reduced by Val(8) GLP-1. In 18-month-old mice, however, the number of Congo red positive dense-core amyloid plaques was reduced. Treatment with Val(8) GLP-1 might prevent or delay neurodegenerative processes. (C) 2012 Elsevier Inc. All rights reserved.
LanguageEnglish
Pages265-276
JournalNeurobiology of Aging
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Neuronal Plasticity
Glucagon-Like Peptide 1
Amyloid beta-Protein Precursor
Long-Term Potentiation
Alzheimer Disease
Amyloid Plaques
Presenilin-1
Incretins
Congo Red
Microglia
Intraperitoneal Injections
Blood-Brain Barrier
Hormones
Inflammation
Enzymes

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Gengler, Simon ; McClean, Paula L. ; McCurtin, Ruth ; Gault, Victor ; Holscher, Christian. / Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 2. pp. 265-276.
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Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. / Gengler, Simon; McClean, Paula L.; McCurtin, Ruth; Gault, Victor; Holscher, Christian.

In: Neurobiology of Aging, Vol. 33, No. 2, 02.2012, p. 265-276.

Research output: Contribution to journalArticle

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