RGD Reference Report - Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity. - Rat Genome Database

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Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity.

Authors: Van Damme, Philip  Bogaert, Elke  Dewil, Maarten  Hersmus, Nicole  Kiraly, Dora  Scheveneels, Wendy  Bockx, Ilse  Braeken, Dries  Verpoorten, Nathalie  Verhoeven, Kristien  Timmerman, Vincent  Herijgers, Paul  Callewaert, Geert  Carmeliet, Peter  Van Den Bosch, Ludo  Robberecht, Wim 
Citation: Van Damme P, etal., Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14825-30. doi: 10.1073/pnas.0705046104. Epub 2007 Sep 5.
RGD ID: 13524860
Pubmed: PMID:17804792   (View Abstract at PubMed)
PMCID: PMC1976195   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0705046104   (Journal Full-text)

Influx of Ca(2+) ions through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors contributes to neuronal damage in stroke, epilepsy, and neurodegenerative disorders such as ALS. The Ca(2+) permeability of AMPA receptors is largely determined by the glutamate receptor 2 (GluR2) subunit, receptors lacking GluR2 being permeable to Ca(2+) ions. We identified a difference in GluR2 expression in motor neurons from two rat strains, resulting in a difference in vulnerability to AMPA receptor-mediated excitotoxicity both in vitro and in vivo. Astrocytes from the ventral spinal cord were found to mediate this difference in GluR2 expression in motor neurons. The presence of ALS-causing mutant superoxide dismutase 1 in astrocytes abolished their GluR2-regulating capacity and thus affected motor neuron vulnerability to AMPA receptor-mediated excitotoxicity. These results reveal a mechanism through which astrocytes influence neuronal functioning in health and disease.

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HotHsd:SD  (Sprague Dawley)

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Gene Gria2 glutamate ionotropic receptor AMPA type subunit 2 Rattus norvegicus

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