Complex I syndrome in striatum and frontal cortex in a rat model of Parkinson disease

Abstract

&NA; Mitochondrial dysfunction named complex I syndrome was observed in striatum mitochondria of rotenone treated rats (2 mg rotenone/kg, i. p., for 30 or 60 days) in an animal model of Parkinson disease. After 60 days of rotenone treatment, the animals showed: (a) 6‐fold increased bradykinesia and 60% decreased locomotor activity; (b) 35‐34% decreases in striatum O2 uptake and in state 3 mitochondrial respiration with malate‐glutamate as substrate; (c) 43–57% diminished striatum complex I activity with 60–71% decreased striatum mitochondrial NOS activity, determined both as biochemical activity and as functional activity (by the NO inhibition of active respiration); (d) 34–40% increased rates of mitochondrial O2•‐ and H2O2 productions and 36–46% increased contents of the products of phospholipid peroxidation and of protein oxidation; and (e) 24% decreased striatum mitochondrial content, likely associated to decreased NO‐dependent mitochondrial biogenesis. Intermediate values were observed after 30 days of rotenone treatment. Frontal cortex tissue and mitochondria showed similar but less marked changes. Rotenone‐treated rats showed mitochondrial complex I syndrome associated with cellular oxidative stress in the dopaminergic brain areas of striatum and frontal cortex, a fact that describes the high sensitivity of mitochondrial complex I to inactivation by oxidative reactions.