Suppression of proteasome C2 contralateral to ischemic lesions in rat brain

Functional as well as structural reorganization takes place in the surround ing and remote brain areas after focal ischemic lesions. In particular, rea ctive or regenerative processes have been described to occur in the contral ateral hemisphere. We used mRNA differential display to gain more insight i nto the molecular mechanisms underlying this type of neuronal plasticity. C ircumscribed unilateral infarcts consistently affecting the forelimb area o f the primary motor cortex were induced photochemically in adult male Wista r rats. The lesion produced significant behavioral asymmetry with subsequen t partial recovery within 1 week. Cloning the genes with altered expression profiles identified the 20S proteasome subunit C2 as a gene whose expressi on level is decreased in contralateral homotopic cortex. Semiquantitative r everse transcription-polymerase chain reaction (RT-PCR) revealed approximat ely 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 p rotein turnover and is critically involved in a variety of regulation proce sses, such as cell cycle, metabolism and differentiation. Our results sugge st that proteasome activity may play also a role in contralateral cortical plasticity occurring after focal cerebral ischemia. (C) 2000 Elsevier Scien ce B.V. All rights reserved.