COENZYME-Q, PEROXIDATION AND CYTOCHROME-OXIDASE FEATURES AFTER PARKINSONS-LIKE DISEASE BY MPTP TOXICITY IN INTRA-SYNAPTIC AND NONSYNAPTIC MITOCHONDRIA FROM MACACA-FASCICULARIS CEREBRAL-CORTEX AND HIPPOCAMPUS -ACTION OF DIHYDROERGOCRIPTINE

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) admin istration on respiratory chain features were studied in synaptic and n on-synaptic mitochondrial populations from cerebral cortex and hippoca mpus of Macaca Fascicularis (Cynomolgus monkey). Enzymatic activity, c ytochrome a + a(3) content and turnover numbers of Complex IV, content s of Coenzyme Q(10), of hydroperoxides and membrane fluidity were asse ssed in non-synaptic ''perikaryal'' and intra-synaptic ''light'' and ' 'heavy'' mitochondria isolated: (a) from the dopaminergic ascending te rminal areas of cerebral cortex of monkeys treated p.o. with dihydroer gocriptine at the dose of 2, 6 or 20 mg/kg/day for 52 weeks; (b) from the dopaminergic terminal areas of hippocampus of monkeys treated p.o. with dihydroergocriptine at the dose of 12 mg/kg/day before and durin g the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). Dihydroergocriptine administration m oderately increased both cytochrome oxidase activity and cytochrome a + a(3) content in ''light'' intra-synaptic mitochondria and hydroperox ides/CoQ(10) ratio in all the types of mitochondria, as a consequence of the enhanced energy metabolism. The Parkinson's-like syndrome by MP TP changed the biochemical investigated parameters, affecting both dir ectly the respiratory chain structures, i.e. by respiratory chain comp lexes inhibition and indirectly, i.e. by free radical mediated damages . MPTP administration negatively influenced Complex IV activity and Tu rnover Number of intra-synaptic mitochondria, without affecting the to tal cytochrome a + a(3) amount. Ln all types of mitochondria and parti cularly on the ''light'' intra-synaptic ones, MPTP-induced lesion enha nced hydroperoxides/Coenzyme Q(10) molar ratio due to the fall in Coen zyme Q(10) levels and the concomitant increase in hydroperoxides. Dihy droergocriptine treatment appeared to be effective in MPTP-treated ani mals in improving those mitochondrial features that probably suffered free radical insults.