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Neuroprotective effects of atorvastatin against glutamate‐induced excitotoxicity in primary cortical neurones
Author(s) -
Bösel Julian,
Gandor Florin,
Harms Christoph,
Synowitz Michael,
Harms Ulrike,
Djoufack Pierre Chryso,
Megow Dirk,
Dirnagl Ulrich,
Hörtnagl Heide,
Fink Klaus B.,
Endres Matthias
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02980.x
Subject(s) - excitotoxicity , neuroprotection , atorvastatin , glutamate receptor , pharmacology , propidium iodide , nmda receptor , chemistry , endocrinology , biochemistry , biology , medicine , apoptosis , programmed cell death , receptor
Abstract Statins [3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors] exert cholesterol‐independent pleiotropic effects that include anti‐thrombotic, anti‐inflammatory, and anti‐oxidative properties. Here, we examined direct protective effects of atorvastatin on neurones in different cell damage models in vitro . Primary cortical neurones were pre‐treated with atorvastatin and then exposed to (i) glutamate, (ii) oxygen–glucose deprivation or (iii) several apoptosis‐inducing compounds. Atorvastatin significantly protected from glutamate‐induced excitotoxicity as evidenced by propidium iodide staining, nuclear morphology, release of lactate dehydrogenase, and mitochondrial tetrazolium metabolism, but not from oxygen–glucose deprivation or apoptotic cell death. This anti‐excitototoxic effect was evident with 2–4 days pre‐treatment but not with daily administration or shorter‐term pre‐treatment. The protective properties occurred independently of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibition because co‐treatment with mevalonate or other isoprenoids did not reverse or attenuate neuroprotection. Atorvastatin attenuated the glutamate‐induced increase of intracellular calcium, which was associated with a modulation of NMDA receptor function. Taken together, atorvastatin exerts specific anti‐excitotoxic effects independent of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibition, which has potential therapeutic implications.