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

Free Radic Biol Med. 2019 May 1:135:274-282. doi: 10.1016/j.freeradbiomed.2019.03.001. Epub 2019 Mar 9.


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.

Keywords: Brain mitochondria; Complex I; H(2)O(2) production; Mitochondrial NOS activity; NO production; Rotenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Electron Transport Complex I / deficiency
  • Electron Transport Complex I / metabolism*
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Gray Matter / drug effects
  • Gray Matter / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Hypokinesia / chemically induced
  • Hypokinesia / metabolism
  • Hypokinesia / pathology
  • Lipid Peroxidation / drug effects
  • Locomotion / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Oxidative Stress / drug effects
  • Oxygen / metabolism*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Rats
  • Rotenone / pharmacology


  • Rotenone
  • Hydrogen Peroxide
  • Electron Transport Complex I
  • Oxygen