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

First Author  Staats KA Year  2012
Journal  Neuroscience Volume  220
Pages  26-31 PubMed ID  22750242
Mgi Jnum  J:192509 Mgi Id  MGI:5465265
Doi  10.1016/j.neuroscience.2012.06.050 Citation  Staats KA, et al. (2012) Dantrolene is neuroprotective in vitro, but does not affect survival in SOD1(G(9)(3)A) mice. Neuroscience 220:26-31
abstractText  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.
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