Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra

Brain Res Mol Brain Res. 1989 May;5(3):203-9. doi: 10.1016/0169-328x(89)90036-3.


Long-term effects of lesions were analyzed in terms of gene expression. Nine months after unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (s. nigra), the remaining dopaminergic (DAergic) neurons (tyrosine hydroxylase (TH) cells determined by immunocytochemistry (ICC] on the lesioned side were atrophic with smaller nucleoli. By in situ hybridization, the DAergic neurons on the lesioned side had a 50% smaller TH-mRNA concentration than on the contralateral non-lesioned side. However, beta-tubulin mRNA concentration in DAergic neurons was unaffected by the lesion. The lesions did not alter TH-mRNA concentration in the contralateral non-lesioned side by comparison with unoperated controls. We propose that chronic lesions have long-term effects on gene expression because of damage sustained during compensatory hyperactivity after the lesion, or because of decreased trophic support from other neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Gene Expression Regulation*
  • Hydroxydopamines
  • Male
  • Nucleic Acid Hybridization
  • Oxidopamine
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred F344
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*
  • Tyrosine 3-Monooxygenase / genetics*
  • Tyrosine 3-Monooxygenase / metabolism


  • Hydroxydopamines
  • RNA, Messenger
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Dopamine