Mitochondrial NAD+-linked State 3 respiration and complex-I activity are compromised in the cerebral cortex of 3-nitropropionic acid-induced rat model of Huntington's disease

Mritunjay Pandey, Merina Varghese, Kizhakke M. Sindhu, Sen Sreetama, A. K. Navneet, Kochupurackal P. Mohanakumar, Rajamma Usha

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Mitochondrial complex-I dysfunction has been observed in patients of Huntington's disease (HD). We assessed whether such a defect is present in the 3-nitropropionic acid (3-NP) model of HD. Rats treated with 3-NP (10-20 mg/kg i.p., for 4 days) exhibited weight loss, gait abnormalities, and striatal lesions with increased glial fibrillary acidic protein immunostaining on fifth and ninth days, while increase in striatal dopamine and loss of tyrosine hydroxylase immunoreactivity were observed on fifth day following treatment. We report for the first time a dose-dependent reduction in complex-I activity in the cerebral cortex when analyzed spectrophotometrically and by blue native-polyacrylamide gel electrophoresis following 3-NP treatment. The citrate synthase normalized activities of mitochondrial complex-I, -II, -(I + III) and -IV were decreased in the cortex of 3-NP treated rats. In addition, succinate driven State 3 respiration was also significantly inhibited in vivo and in the isolated mitochondria. These findings taken together with the observation of a significant decrease in vivo but not in vitro of State 3 respiration with NAD+-linked substrates, suggest complex-I dysfunction in addition to irreversible inhibition of complex-II and succinate dehydrogenase activity as a contributing factor in 3-NP-induced cortico-striatal lesion.

Original languageEnglish
Pages (from-to)420-434
Number of pages15
JournalJournal of Neurochemistry
Volume104
Issue number2
DOIs
StatePublished - Jan 2008

Keywords

  • BN-PAGE
  • Cortico-striatal neurodegeneration
  • Electron transport chain
  • Footprint analysis
  • GFAP
  • Striatal dopamine
  • Succinate dehydrogenase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Mitochondrial NAD+-linked State 3 respiration and complex-I activity are compromised in the cerebral cortex of 3-nitropropionic acid-induced rat model of Huntington's disease'. Together they form a unique fingerprint.

Cite this