Suppression of proteasome C2 contralateral to ischemic lesions in rat brain

Functional as well as structural reorganization takes place in the surrounding and remote brain areas after focal ischemic lesions. In particular, reactive or regenerative processes have been described to occur in the contralateral hemisphere. We used mRNA differential display to gain more insight into the molecular mechanisms underlying this type of neuronal plasticity. Circumscribed unilateral infarcts consistently affecting the forelimb area of the primary motor cortex were induced photochemically in adult male Wistar rats. The lesion produced significant behavioral asymmetry with subsequent partial recovery within 1 week. Cloning the genes with altered expression profiles identified the 20S proteasome subunit C2 as a gene whose expression level is decreased in contralateral homotopic cortex. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed approximately twofold lower proteasome C2 mRNA levels in the lesion group as compared with the sham-operated group. The proteasome serves as the central enzyme of non-lysosomal protein degradation. It is responsible for intracellular protein turnover and is critically involved in a variety of regulation processes, such as cell cycle, metabolism and differentiation. Our results suggest that proteasome activity may play also a role in contralateral cortical plasticity occurring after focal cerebral ischemia.