Mitochondrial Complex I dysfunction in experimental Parkinsonism.

ZAOBORNYJ T; VALDEZ LB; BANDEZ MJ; NAVARRO A; BOVERIS A

Londres

Congreso; 16th Biennial Meeting of the Society for Free Radical Research International.; 2012

Society for Free Radical Research International

Complex factors contribute to the appearance of Parkinson’s disease (PD) but mitochondrial dysfunction and a decreased capacity to produce ATP in the affected brain areas are constant features. The Parkinsonism model used consisted in the chronic administration of rotenone (2 mg/kg weight, i.p. daily) during 30 or 60 days. Rotenone-treated rats showed a 17% and 35% decreased striatal O2 uptake. The same phenomenon was observed in isolated striatal mitochondria: state 3 respiration using malate-glutamate as substrates decreased 13% and 30% after 30 and 60 days of treatment. C omplex I activity decreased after 30 and 60 days of rotenone administration by 17% and 57%, respectively. A similar reduction was observed in biochemical mtNOS (27% and 62%, in 30 and 60 days rotenone-treated rats) and in functional mtNOS activities (29% and 71%). Linear correlations were obtained between mitochondrial complex I activity and either malate-glutamate supported state 3 O2 uptake (r2 = 0.97) or mtNOS biochemical (r2 = 0.98) and functional activities (r2 = 0.98), indicating that the complex I activity decline is associated to mtNOS activity reduction and to striatum mitochondrial respiration impairment. In addition, rats treated with rotenone increased the O2 •- production rates by 13% and 37%, in agreement with an increased striatal mitochondria phospholipids (36%) and protein (35%) oxidation. The mitochondrial dysfunction detected in striatum in rotenone-treated rats is described as “complex I syndrome”, a concept that links the two mutually dependent conditions observed in PD: brain mitochondrial dysfunction and brain mitochondrial oxidative damage.