Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging

Brain Res Mol Brain Res. 1992 Mar;13(1-2):63-73. doi: 10.1016/0169-328x(92)90045-d.

Abstract

Slow neuron regression develops during the adult phase of life in select brain systems of mammals. We describe a model in adult rats that resolves several phases in a slow atrophic process that differentially influences levels of mRNA and protein for tyrosine hydroxylase (TH). Responses of striatal dopaminergic markers to 6-hydroxydopamine (6-OHDA) lesions in rats indicated that the striatal terminals maintained TH protein, despite greater than 3-fold loss of TH mRNA in the substantia nigra pars compacta (SNC) cell bodies whose axons project to the striatum. The loss of TH mRNA/cell was progressive up to 9 months, whereas SNC cell body shrinkage stabilized by 3 months post-lesioning. Consideration of possible mechanisms in protein turnover motivated a search for PEST motifs in the TH of rats and other vertebrates that could be a point of regulation by altering the rate of TH protein turnover.

Publication types

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

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Aging
  • Amino Acid Sequence
  • Animals
  • Biogenic Monoamines / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / growth & development
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Homovanillic Acid / metabolism
  • Humans
  • Hydroxyindoleacetic Acid / metabolism
  • Immunohistochemistry
  • Male
  • Molecular Sequence Data
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / physiology*
  • Norepinephrine / metabolism
  • Nucleic Acid Hybridization
  • Oxidopamine / pharmacology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred F344
  • Sequence Homology, Nucleic Acid
  • Serotonin / metabolism
  • Substantia Nigra / drug effects
  • Substantia Nigra / growth & development
  • Substantia Nigra / metabolism*
  • Tyrosine 3-Monooxygenase / genetics*

Substances

  • Biogenic Monoamines
  • RNA, Messenger
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid