Elsevier

Neuroscience Letters

Volume 343, Issue 2, 5 June 2003, Pages 81-84
Neuroscience Letters

The AMPA receptor antagonist NBQX prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis

https://doi.org/10.1016/S0304-3940(03)00314-8Get rights and content

Abstract

α-Amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated excitotoxicity has been implicated in the selective motor neuron loss in amyotrophic lateral sclerosis (ALS). The extent to which excitotoxicity contributes to motor neuron death remains incompletely understood. We therefore tested the potent and selective AMPA/kainate receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) on motor neurons in culture and in the G93A mouse model for familial ALS. Kainate-induced currents and changes in intracellular Ca2+ concentration were measured with the perforated patch clamp technique combined with Ca2+ imaging, motor neuron death was quantified by counting experiments and G93A mice were treated with saline or 8 mg/kg NBQX. NBQX blocked kainate-induced currents and concomitant changes in intracellular Ca2+, prevented the kainate-induced motor neuron death, and prolonged survival of G93A mice.

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Acknowledgments

We thank V. Thijs for his help with statistical analysis. This work was supported by grants from the Fund for Scientific Research Flanders (F.W.O. Vlaanderen) and the University of Leuven. P.V.D. is a Research Assistant and W.R. is a Clinical Investigator of the Fund for Scientific Research Flanders. This research project is part of the IUAP Phase V (Molecular Genetics and Cell Biology).

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