title: Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) pathology occurs in part as the result of excessive production of β-amyloid (Aβ). Metabotropic glutamate receptor 5 (mGluR5) is now considered a receptor for Aβ and consequently contributes to pathogenic Aβ signaling in AD.
  
  
  RESULTS
  Genetic deletion of mGluR5 rescues the spatial learning deficits observed in APPswe/PS1ΔE9 AD mice. Moreover, both Aβ oligomer formation and Aβ plaque number are reduced in APPswe/PS1ΔE9 mice lacking mGluR5 expression. In addition to the observed increase in Aβ oligomers and plaques in APPswe/PS1ΔE9 mice, we found that both mTOR phosphorylation and fragile X mental retardation protein (FMRP) expression were increased in these mice. Genetic deletion of mGluR5 reduced Aβ oligomers, plaques, mTOR phosphorylation and FMRP expression in APPswe/PS1ΔE9 mice.
  
  
  CONCLUSIONS
  Thus, we propose that Aβ activation of mGluR5 appears to initiate a positive feedback loop resulting in increased Aβ formation and AD pathology in APPswe/PS1ΔE9 mice via mechanism that is regulated by FMRP.
authors.forename: Alison
authors.initials: A
authors.lastname: Hamilton
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Esseltine
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: DeVries
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cregan
authors.affiliation: The J, Allyn Taylor Centre for Cell Biology, Robarts Research Institute, The University of Western Ontario, 100 Perth Dr, London, Ontario N6A 5 K8, Canada. ferguson@robarts.ca.
authors.forename: Stephen S G
authors.initials: SS
authors.lastname: Ferguson
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D018782:Maze Learning; D008569:Memory Disorders / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D010641:Phenotype; D064529:Receptor, Metabotropic Glutamate 5 / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051860:Fragile X Messenger Ribonucleoprotein 1; D007295:Inositol Phosphates; D064529:Receptor, Metabotropic Glutamate 5; D058570:TOR Serine-Threonine Kinases