Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones

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Item Type:	Article
Title:	Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones
Creators Name:	Boesel, J., Gandor, F., Harms, C., Synowitz, M., Harms, U., Djoufack, P.C., Megow, D., Dirnagl, U., Hoertnagl, H., Fink, K.B. and Endres, M.
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.
Keywords:	3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors, Excitotoxicity, Neuroprotection, Statins
Source:	Journal of Neurochemistry
ISSN:	0022-3042
Publisher:	Blackwell Publishing
Volume:	92
Number:	6
Page Range:	1386-1398
Date:	1 January 2005
Official Publication:	https://doi.org/10.1111/j.1471-4159.2004.02980.x
PubMed:	View item in PubMed

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