Dantrolene is neuroprotective in vitro, but does not affect survival in SOD1G93A mice

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 (SOD1G93A) 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.

► Dantrolene protects motor neurons in vitro against excitotoxic cell death. ► Dantrolene administration does not affect onset, disease duration or survival of ALS mice. ► Dantrolene administration does not affect the number of motor neurons or ubiquitination in ALS mice.