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

2007; National Academy of Sciences; Volume: 104; Issue: 37 Linguagem: Inglês

10.1073/pnas.0705046104

1091-6490

Philip Van Damme, Elke Bogaert, Maarten Dewil, Nicole Hersmus, Dora Kiraly, Wendy Scheveneels, Ilse Bockx, Dries Braeken, Nathalie Verpoorten, Kristien Verhoeven, Vincent Timmerman, Paul Herijgers, Geert Callewaert, Peter Carmeliet, Ludo Van Den Bosch, Wim Robberecht,

Neurogenesis and neuroplasticity mechanisms

Influx of Ca 2+ ions through α-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.