DECREASE IN THE PROTEASOME ACTIVITY ENHANCE REMYELINATION IN CUPRIZONE INTOXICATED ANIMALS BY AN IMPROVEMENT IN MITOCHONDRIAL ACTIVITY

MILLET V, SOTO E, PASQUINI J, PASQUINI LA

Pinamar, Buenos Aires, Argentina

Congreso; SAIB -PABMB-SAN; 2005

SAIB -PABMB-SAN

Introduction: Addition of lactacystin to oligodendroglial cell cultures induces their exit from the cell cycle and their differentiation. Recently results in Swiss male mice undergoing a spontaneous remyelination after cuprizone-induced demyelination (CPZ) were intracraneally injected (ICI) in corpus callosum with lactacystin at day 5 of their remyelination period (RP) and evaluated 10 days after. We observed an increase in myelin deposition, total proteins, myelin galactolipids and in MBP isoforms expression related to control. Our results obtained in primary cultures of OLGcs suggest that CPZ induces demyelination by decreasing the activity of mitochondrial complexes in these cells, with a lost in energy production and an increase in the production of free radicals. Aims: Evaluate changes in the mitochondrial complexes activity (I, I/III and II/III) in mice brains during their CPZ intoxication and spontaneous remyelination. The response of CPZ intoxicated (D) and control animals (C) ICI at day 5 of RP with vehicle or lactacystin (CV, CL, DV and DL).Results: D show a decrease in the activity of complexes correlated to the demyelination process compared to C. During the RP, D enhance their mitochondrial activity. DL and CL complexes activity are enhanced in relation to DV and CV respectively.Conclusion: The enhance remyelination obtained by a decrease in the proteasome activity is due, at less in part, to the increase of activity of mitochondrial complexes.