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

Neurobiol Aging. 2012 Feb;33(2):265-76. doi: 10.1016/j.neurobiolaging.2010.02.014. Epub 2010 Mar 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology*
  • Animals
  • Glucagon-Like Peptide 1 / pharmacology*
  • Long-Term Potentiation / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Plasticity / drug effects*
  • Peptide Fragments / pharmacology*
  • Plaque, Amyloid / complications
  • Plaque, Amyloid / drug therapy*
  • Plaque, Amyloid / physiopathology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Synapses
  • Treatment Outcome

Substances

  • Peptide Fragments
  • Presenilin-1
  • glucagon-like peptide 1 (7-36), Val(8)-
  • Glucagon-Like Peptide 1