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Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) pathology occurs in part as the result of excessive production of ?-amyloid (A?). Metabotropic glutamate receptor 5 (mGluR5) is now considered a receptor for A? and consequently contributes to pathogenic A? signaling in AD.Genetic deletion of mGluR5 rescues the spatial learning deficits observed in APPswe/PS1?E9 AD mice. Moreover, both A? oligomer formation and A? plaque number are reduced in APPswe/PS1?E9 mice lacking mGluR5 expression. In addition to the observed increase in A? oligomers and plaques in APPswe/PS1?E9 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 A? oligomers, plaques, mTOR phosphorylation and FMRP expression in APPswe/PS1?E9 mice.Thus, we propose that A? activation of mGluR5 appears to initiate a positive feedback loop resulting in increased A? formation and AD pathology in APPswe/PS1?E9 mice via mechanism that is regulated by FMRP.

SUBMITTER: Hamilton A

PROVIDER: S-EPMC4050478 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.

Hamilton Alison A Esseltine Jessica L JL DeVries Rebecca A RA Cregan Sean P SP Ferguson Stephen S G SS

Molecular brain 20140529

<h4>Background</h4>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.<h4>Results</h4>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 ...[more]

PMID: 24886239

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Dataset Information

Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.

Publications

Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.

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