Sensory-motor performance after acute glutathione depletion by L-buthionine sulfoximine injection into substantia nigra pars compacta

Behav Brain Res. 2014 Sep 1:271:286-93. doi: 10.1016/j.bbr.2014.05.066. Epub 2014 Jun 6.

Abstract

Glutathione is the major antioxidant in the living cells. Its deficit has been linked to neurodegenerative disorders as Parkinson's disease but its role in the etiology of nigral degeneration and sensory-motor performance has been poorly explored. To evaluate the effect of glutathione depletion on nigro-striatal oxidative metabolism and sensory-motor performance in rats, l-buthionine sulfoximine (15 mM) or saline solution was injected into substantia nigra pars compacta (SNpc). Then, oxidative metabolism was studied 24h and 7 days later in SNpc and corpus striatum (CS). Tyrosine hydroxylase and GFAP immunohistochemistry assays were carried out at 7 days. In addition, animals were evaluated in open field, adhesive removal, staircase and traverse beam tests. Glutathione depletion induced compensatory response in catalase activity and glial response in the in SNpc and no oxidative damage was observed. However, a loss in dopaminergic cells was found. At the same time, animals with glutathione depletion have shown poor performance in behavioral tests except for staircase test. These results suggest that glutathione depletion can be related to sensory-motor dysfunction.

Keywords: Antioxidant enzymes; Astrocytes; Dopaminergic cell; Glutathione; Malondialdehyde; Sensory-motor function.

MeSH terms

  • Animals
  • Buthionine Sulfoximine / toxicity*
  • Corpus Striatum / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism*
  • Locomotion / drug effects
  • Male
  • Microinjections
  • Motor Activity / drug effects
  • Pars Compacta / metabolism*
  • Psychomotor Performance / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Buthionine Sulfoximine
  • Tyrosine 3-Monooxygenase
  • Glutathione