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


ABSTRACT: 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.

SUBMITTER: Van Damme P 

PROVIDER: S-EPMC1976195 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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

Van Damme Philip P   Bogaert Elke E   Dewil Maarten M   Hersmus Nicole N   Kiraly Dora D   Scheveneels Wendy W   Bockx Ilse I   Braeken Dries D   Verpoorten Nathalie N   Verhoeven Kristien K   Timmerman Vincent V   Herijgers Paul P   Callewaert Geert G   Carmeliet Peter P   Van Den Bosch Ludo L   Robberecht Wim W  

Proceedings of the National Academy of Sciences of the United States of America 20070905 37


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 AM  ...[more]

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