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Atorvastatin alters expression of caveolin-1 and PSD-95 in mouse brain

Abstract

Membrane/lipid rafts (MLR) are plasmalemmal microdomains enriched in sphingolipids, cholesterol and the protein caveolin (Cav) and are essential for neuronal signaling and synaptic development/stabilization. Statins inhibit HMG-CoA reductase, the rate-limiting enzyme involved in cholesterol biosynthesis. There exists much controversy over the effects of statins on neuronal function. We investigated the impact of long-term atorvastatin treatment (5 mg/kg/d for 7 months by oral gavage) on cognitive behavior and brain biochemistry in mice. Atorvastatin treatment resulted in significantly longer primary escape latencies on probe trial day 1 as assessed by the Barnes maze, indicating impairment of hippocampal- dependent short-term memory. No motor deficits were observed as assessed by RotaRod. Sucrose gradient fraction used to isolate MLR from hippocampal tissue showed a significant reduction in the protein expression of Cav-1 and the post-synaptic density marker PSD-95 from MLR in atorvastatin-treated mice. These data suggest that statins reduce MLR protein expression, which could provide an explanation for the phenotypic changes in cognition. Such a finding may provide a biochemical mechanism for cognitive and behavioral changes from statins found in the literature

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