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

Autor:	Rene Verbesselt, Wendy Scheveneels, Kim A. Staats, L. Van Den Bosch, Wim Robberecht, M. Van Rillaer, P. Van Damme
Rok vydání:	2012
Předmět:	Chemistry Ryanodine receptor General Neuroscience Neurodegeneration SOD1 Excitotoxicity chemistry.chemical_element AMPA receptor Calcium Pharmacology medicine.disease_cause medicine.disease Neuroprotection Dantrolene medicine Neuroscience medicine.drug
Zdroj:	Neuroscience. 220:26-31
ISSN:	0306-4522
DOI:	10.1016/j.neuroscience.2012.06.050
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::833aeb9f0ca47f79a048b3d1b0f31b5f https://doi.org/10.1016/j.neuroscience.2012.06.050 Zobrazit plný text záznamu Full Text from ScienceDirect