Rosuvastatin induces delayed preconditioning against L-glutamate excitotoxicity in cultured cortical neurons

Domoki, Ferenc and Kis, Béla and Gaspar, Tamás and Snipes, James A. and Bari, Ferenc (2010) Rosuvastatin induces delayed preconditioning against L-glutamate excitotoxicity in cultured cortical neurons. NEUROCHEMISTRY INTERNATIONAL, 56 (3). pp. 404-409. ISSN 0197-0186

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Abstract

We tested whether rosuvastatin (RST) protected against excitotoxic neuronal cell death in rat primary cortical neuronal cultures. L-Glutamate (200 mu M, 1h) reduced neuronal viability (% of naive controls, mean +/- SEM, n = 8-32, *p < 0.05) from 100 +/- 2% to 60 +/- 1% , but pretreatment with RST (0.5 mu M, 3 days) increased survival to 88 +/- 2%*. RST-induced neuroprotection was not affected by co-application with mevalonate (10 mu M), although the same dose of mevalonate fully prevented the neurotoxic effects of a high dose (20 mu M) of RST. RST (0.5 mu M) pretreatment did not affect mitochondrial membrane potential or superoxide anion levels in quiescent neurons. However, RST pretreatment blunted elevations in free intracellular Ca(2+) and reduced increases in superoxide anion levels following glutamate exposure. Manganese superoxide dismutase (SOD), copper-zinc SOD, catalase, and reduced glutathione levels were unaffected by RST pretreatment. In contrast, acute, one time RST application did not affect either baseline or L-glutamate-induced increases in superoxide levels. In summary, three-day RST pretreatment induces resistance to the excitotoxic effect Of L-glutamate in cultured neurons apparently by a mechanism that is independent of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition. The delayed neuroprotection by RST against excitotoxicity does not involve sustained mitochondrial depolarization or superoxide anion production as initiating events, although it is associated with reduced Ca(2+) influx and superoxide anion production upon L-glutamate challenge. (C) 2009 Elsevier Ltd. All rights reserved.

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