• Neuroscience · Sep 2012

    Dantrolene is neuroprotective in vitro, but does not affect survival in SOD1(G⁹³A) mice.

    • K A Staats, M Van Rillaer, W Scheveneels, R Verbesselt, P Van Damme, W Robberecht, and L Van Den Bosch.
    • Laboratory of Neurobiology and Leuven research Institute for Neurodegenerative Disorders (LIND), KU Leuven, Belgium.
    • Neuroscience. 2012 Sep 18;220:26-31.

    AbstractAmyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease. One of the proposed disease mechanisms is excitotoxicity, in which excessive cytosolic calcium causes neuronal death. Although most calcium may originate from the extracellular space through activation of calcium-permeable AMPA receptors, we investigated in this study the contribution of endoplasmic reticulum calcium release by blocking the ryanodine receptor (RyR) using dantrolene. In vitro, dantrolene provides a significant protection to motor neurons exposed to a brief excitotoxic insult. However, daily administration of dantrolene to mice overexpressing superoxide dismutase 1 glycine to alanine at position 93 (SOD1(G93A)) does affect neither survival nor the number of motor neurons and ubiquitin aggregates indicating that calcium release through RyRs does not contribute to the selective motor neuron death in this animal model for ALS.Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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