title: Dantrolene is neuroprotective in vitro, but does not affect survival in SOD1(G⁹³A) mice.
abstract: Amyotrophic 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.
authors: Laboratory of Neurobiology and Leuven research Institute for Neurodegenerative Disorders (LIND), KU Leuven, Belgium.
authors: K A
authors: KA
authors: Staats
authors: M
authors: M
authors: Van Rillaer
authors: W
authors: W
authors: Scheveneels
authors: R
authors: R
authors: Verbesselt
authors: P
authors: P
authors: Van Damme
authors: W
authors: W
authors: Robberecht
authors: L
authors: L
authors: Van Den Bosch
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D018696:Neuroprotective Agents; D019837:Ryanodine Receptor Calcium Release Channel; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003620:Dantrolene; D002118:Calcium