Back to Search
Start Over
Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease
- Source :
- Molecular Brain
- Publisher :
- Springer Nature
-
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.
- Subjects :
- Inositol Phosphates
Receptor, Metabotropic Glutamate 5
Biology
Motor Activity
Learning and memory
Pathogenesis
Fragile X Mental Retardation Protein
Mice
Cellular and Molecular Neuroscience
Alzheimer Disease
mental disorders
medicine
Animals
Humans
Receptor
Maze Learning
mGluR5
Molecular Biology
PI3K/AKT/mTOR pathway
Mice, Knockout
APPswe/PS1ΔE9
Memory Disorders
Amyloid beta-Peptides
Metabotropic glutamate receptor 5
TOR Serine-Threonine Kinases
Research
Cell Membrane
Beta amyloid
medicine.disease
Cell biology
Disease Models, Animal
Phenotype
Phosphorylation
Psychopharmacology
Signal transduction
Alzheimer's disease
Cognition Disorders
FMRP
Neuroscience
Alzheimer’s disease
Gene Deletion
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17566606
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Brain
- Accession number :
- edsair.doi.dedup.....13de4a50031beeca38c0de5b1af38aeb
- Full Text :
- https://doi.org/10.1186/1756-6606-7-40