Increased sensitivity of striatal dopamine release to H2O 2 upon chronic rotenone treatment

Elisaveta Milusheva, M. Baranyi, A. Kittel, B. Sperlágh, E. Vízi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

It is believed that both mitochondrial dysfunction and oxidative stress play important roles in the pathogenesis of Parkinson's disease (PD). We studied the effect of chronic systemic exposure to the mitochondrial inhibitor rotenone on the uptake, content, and release of striatal neurotransmitters upon neuronal activity and oxidative stress, the latter simulated by H2O 2 perfusion. The dopamine content in the rat striatum is decreased simultaneously with the progressive loss of tyrosine hydroxylase (TH) immunoreactivity in response to chronic intravenous rotenone infusion. However, surviving dopaminergic neurons take up and release only a slightly lower amount of dopamine (DA) in response to electrical stimulation. Striatal dopaminergic neurons showed increased susceptibility to oxidative stress by H 2O2, responding with enhanced release of DA and with formation of an unidentified metabolite, which is most likely the toxic dopamine quinone (DAQ). In contrast, the uptake of [3H]choline and the electrically induced release of acetylcholine increased, in coincidence with a decline in its D2 receptor-mediated dopaminergic control. Thus, oxidative stress-induced dysregulation of DA release/uptake based on a mitochondrial deficit might underlie the selective vulnerability of dopaminergic transmission in PD, causing a self-amplifying production of reactive oxygen species, and thereby contributing to the progressive degeneration of dopaminergic neurons.

Original languageEnglish
Pages (from-to)133-142
Number of pages10
JournalFree Radical Biology and Medicine
Volume39
Issue number1
DOIs
Publication statusPublished - Jul 1 2005

Fingerprint

Corpus Striatum
Rotenone
Oxidative stress
Dopaminergic Neurons
Dopamine
Oxidative Stress
Neurons
Parkinson Disease
Poisons
Tyrosine 3-Monooxygenase
Therapeutics
Metabolites
Choline
Intravenous Infusions
Electric Stimulation
Acetylcholine
Neurotransmitter Agents
Rats
Reactive Oxygen Species
Perfusion

Keywords

  • Acetylcholine
  • Dopamine
  • H O
  • Oxidative stress
  • Parkinson's disease
  • Release
  • Striatum

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Increased sensitivity of striatal dopamine release to H2O 2 upon chronic rotenone treatment. / Milusheva, Elisaveta; Baranyi, M.; Kittel, A.; Sperlágh, B.; Vízi, E.

In: Free Radical Biology and Medicine, Vol. 39, No. 1, 01.07.2005, p. 133-142.

Research output: Contribution to journalArticle

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