Title: GluR2 deficiency accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis
Authors: Van Damme, Philip ×
Braeken, Dries
Callewaert, Geert
Robberecht, Wim
Van Den Bosch, Ludo #
Issue Date: Jul-2005
Publisher: Association of the Journal of Neuropathology and Experimental Neurology
Series Title: Journal of Neuropathology and Experimental Neurology vol:64 issue:7 pages:605-612
Abstract: AMPA receptor-mediated excitotoxicity has been implicated in the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Motor neurons in vitro are particularly vulnerable to excessive AMPA receptor stimulation and one of the factors underlying this selective vulnerability is the presence of a large proportion of Ca2+ -permeable (i.e. GluR2-lacking) AMPA receptors. However, the precise role of GluR2-lacking AMPA receptors in motor neuron degeneration remains to be defined. We therefore studied the impact of GluR2 deficiency on motor neuron death in vitro and in vivo. Cultured motor neurons from GluR2-deficient embryos displayed an increased Ca2+ influx through AMPA receptors and an increased vulnerability to AMPA receptor-mediated excitotoxicity. We deleted the GluR2 gene in mutant SOD1G93A mice by crossbreeding them with GluR2 knockout mice. GluR2 deficiency clearly accelerated the motor neuron degeneration and shortened the life span of mutant SOD1G93A mice. These findings indicate that GluR2 plays a pivotal role in the vulnerability of motor neurons in vitro and in vivo, and that therapies that limit Ca2+ entry through AMPA receptors might be beneficial in ALS patients.
ISSN: 0022-3069
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Physiology Section (-)
Department of Cellular and Molecular Medicine - miscellaneous
Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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