A novel protein induced in cortical epileptic focus of rat cerebrum: A possible linkage to epileptogenesis

Abstract

To precisely evaluate a protein-related mechanism of epileptogenesis, we quantitatively analyzed the 70-kDa protein (namely, P70), a specific protein found in the cobalt-induced epileptic focus, and examined its effect on the electrocorticogram (ECoG) and cortical neurons in cerebral slices and its immunocytochemical localization in rats. Cobalt-induced cortical epileptogenic cortex exhibited a marked induction of P70. Its initiation time was ahead of the generation of epileptogenic activities. The anticonvulsant phenytoin (PHT) attenuated the cobalt-induced epileptogenic activities, but failed to suppress protein induction. Injection of this protein into the motor region of normal rat cerebral cortex elicited an epileptic ECoG and behavioral seizures. It also caused epileptiform activity with paroxysmal depolarization shifts in cortical neurons. These epileptogenic phenomena elicited by P70 were abolished by prior treatment with PHT or phenobarbital. Immunocytochemical analysis with an antiserum against P70 revealed that the reactivity was confined to pyramidal cells only in the region of the focus and was mainly localized on somatic, dendritic, and nuclear membranes and microtubles. These findings suggest that P70 may be linked to epileptogenesis.