Electroconvulsive seizure increases phosphorylation of PKC substrates, including GAP-43, MARCKS, and neurogranin, in rat brain.

Protein kinase C (PKC) has been suggested as a molecular target related to the pathogenetic and therapeutic mechanisms of mood disorders in which electroconvulsive seizure (ECS) is effective. However, the reports concerning the effects of ECS on PKC are anecdotal and need further clarification. In this study, we examined the effects of ECS treatment on the phosphorylation of PKC substrates, including GAP-43, MARCKS, and neurogranin. Immunoblot using anti-p-PKC substrate antibodies revealed that a single ECS treatment induced temporal changes in the phosphorylation level of PKC substrates in rat brain, reflecting the effects on PKC activity. Phosphorylation of GAP-43 and MARCKS, representative PKC substrates related to synaptic remodeling, increased from 5 to 30 min, after a transient decrease at 0 min immediately after ECS, and returned to basal levels at 60 min in rat frontal cortex, hippocampus, and cerebellum. Phosphorylation of neurogranin, another PKC substrate, showed a similar pattern of temporal changes in the frontal cortex and hippocampus. Immunohistochemical analysis revealed that p-GAP-43 and p-MARCKS were densely stained throughout the neuronal cells of the prefrontal cortex and hippocampus, and the Purkinje cells of cerebellum, after ECS treatment. Brief and transient activation of PKC may be translated into long-term biochemical changes, resulting in synaptic plasticity. Taken together, the acute effects of ECS on PKC activity, which could be an underpinning of long-term biochemical changes induced by ECS, may contribute to understand the molecular mechanism of ECS.