Atorvastatin (ATV), a 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, exerts beneficial effects on stroke through several pleiotropic mechanisms. However, its role following cerebral ischemia is not completely understood yet. We evaluated the effect of ATV treatment on the synaptic adhesion proteins after a transient middle cerebral artery occlusion (t-MCAO) model in rats. Ischemic male Wistar rats were treated with 10 mg/kg ATV. The first dose was 6 hr after reperfusion, then every 24 hr for 3 days. Our findings showed that ATV treatment produced an increase in pAkt ser473 and a decrease in pMAPK 44/ 42 protein levels 12 and 24 hr postischemia in the cerebral cortex and the hippocampus. However, p120 catenin and aN-catenin became drastically increased throughout the temporal course of postischemia treatment (12-72 hr), mainly in the hippocampus. Neurological recovery was observed at 48 and 72 hr, supported by a significant reduction of infarct volume, neuronal loss, and glial hyperreactivity after 72 hr of postischemia treatment with ATV. ATV treatment also up-regulated the association of p120 ctn , aN-catenin to PSD-95, accompanied by a reduction of RhoA activation and the recovery of MAP2 immunoreactivity, these being significantly affected by the focal cerebral ischemia. Our findings suggested that p120 ctn and aN-catenin synaptic adhesion proteins are crucial molecular targets in ATV-mediated neuroprotection and neuronal plasticity after focal cerebral ischemia. V V C 2010 Wiley-Liss, Inc.
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