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Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones.
J Neurochem. 2005 Mar; 92(6):1386-98.JN

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.

Authors+Show Affiliations

Klinik und Poliklinik für Neurologie, Charité- Universitätsmedizin Berlin, Campus Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15748157

Citation

Bösel, Julian, et al. "Neuroprotective Effects of Atorvastatin Against Glutamate-induced Excitotoxicity in Primary Cortical Neurones." Journal of Neurochemistry, vol. 92, no. 6, 2005, pp. 1386-98.
Bösel J, Gandor F, Harms C, et al. Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005;92(6):1386-98.
Bösel, J., Gandor, F., Harms, C., Synowitz, M., Harms, U., Djoufack, P. C., Megow, D., Dirnagl, U., Hörtnagl, H., Fink, K. B., & Endres, M. (2005). Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. Journal of Neurochemistry, 92(6), 1386-98.
Bösel J, et al. Neuroprotective Effects of Atorvastatin Against Glutamate-induced Excitotoxicity in Primary Cortical Neurones. J Neurochem. 2005;92(6):1386-98. PubMed PMID: 15748157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. AU - Bösel,Julian, AU - Gandor,Florin, AU - Harms,Christoph, AU - Synowitz,Michael, AU - Harms,Ulrike, AU - Djoufack,Pierre Chryso, AU - Megow,Dirk, AU - Dirnagl,Ulrich, AU - Hörtnagl,Heide, AU - Fink,Klaus B, AU - Endres,Matthias, PY - 2005/3/8/pubmed PY - 2005/4/23/medline PY - 2005/3/8/entrez SP - 1386 EP - 98 JF - Journal of neurochemistry JO - J Neurochem VL - 92 IS - 6 N2 - 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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15748157/Neuroprotective_effects_of_atorvastatin_against_glutamate_induced_excitotoxicity_in_primary_cortical_neurones_ L2 - https://doi.org/10.1111/j.1471-4159.2004.02980.x DB - PRIME DP - Unbound Medicine ER -