Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice.
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.
Gengler
Simon
S
School of Biomedical Sciences, Ulster University, Coleraine, UK.
McClean
Paula L
PL
McCurtin
Ruth
R
Gault
Victor A
VA
Hölscher
Christian
C
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D013569:Synapses; D016896:Treatment Outcome
D010446:Peptide Fragments; D053764:Presenilin-1; C555025:glucagon-like peptide 1 (7-36), Val(8)-; D052216:Glucagon-Like Peptide 1