The Effects of Cyclosporin A on the Signal Transduction System in the Rat Brain / 대한정신약물학회지

ABSTRACT

The most important molecular mechanisms of intraneuronal signal transduction are those mediated by calcium and reversible protein phosphorylation. Although many studies pursued the activation of the protein kinases in the nervous system, there are only few reports focused on the protein phosphatases. In this article, the authors report the effects of cyclosporin A (CSA), an inhibitor of calcineurin, on the calcium signaling-related molecules such as ERKs, calmodulin-dependent kinase II (CaMKII) and CREB in the rat hippocampus. The authors also report the effects of cyclosporin A on the electroconvulsive shock (ECS)-induced seizure and the activation of ERKs. Calcineurin is a protein phosphatase that is abundant in the brain and regulated by calcium and calmodulin. It is proposed that calcineurin plays central roles in the synaptic plasticity and neuronal apoptosis. CSA (50 mg/kg) increased the phosphorylation of ERK, CaMKII and CREB. The treatment of of CSA increased the duration of tonic phase of seizure induced by ECS and augmented the phosphorylation of ERKs after ECS. These results suggested the protective role of calcineurin against the excessive electrical and molecular activities in the brain.