TY - JOUR
T1 - Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice
AU - Gengler, Simon
AU - McClean, Paula L.
AU - McCurtin, Ruth
AU - Gault, Victor
AU - Holscher, Christian
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
U2 - 10.1016/j.neurobiolaging.2010.02.014
DO - 10.1016/j.neurobiolaging.2010.02.014
M3 - Article
SN - 1558-1497
VL - 33
SP - 265
EP - 276
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 2
ER -
