Localization and functional significance of striatal neurons immunoreactive to aromatic L-amino acid decarboxylase or tyrosine hydroxylase in rat Parkinsonian models

Brain Res. 2003 Apr 18;969(1-2):135-46. doi: 10.1016/s0006-8993(03)02291-1.

Abstract

Striatal neurons which are immunoreactive (ir) to aromatic L-amino-acid decarboxylase (AADC) or tyrosine hydrodroxylase (TH) may play a role in the decarboxylation of L-DOPA to dopamine (DA) in advanced stages of Parkinson's disease (PD). However, the functional significance of these neurons and the mechanisms responsible for their induction remain to be clarified. In this study, rats were subjected to different types of dopaminergic or serotonergic denervation and L-DOPA injection to study the effects on these neurons. AADC-ir neurons were found in both normal and DA-denervated striata, and no significant differences in their number and distribution were induced following different types of denervation or L-DOPA administration. TH-ir neurons were only found in DA-denervated striata. However, TH-ir neurons did not appear in those areas with maximal DA depletion, but rather were observed near spared or partially lesioned DA terminals. The population of AADC-ir neurons may make a significant contribution to the effects of exogenous L-DOPA in advanced stages of PD. In addition, TH-ir neurons may contribute to these effects, since we have detected AADC-ir in TH-ir neurons using confocal laser scanning microscopy. Finally, neither L-DOPA therapy nor serotonergic denervation induces significant changes in the number or distribution of these neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology
  • Corpus Striatum / surgery
  • Denervation
  • Dopamine / deficiency
  • Dopamine Agents / metabolism
  • Dopamine Agents / pharmacology
  • Female
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Levodopa / metabolism
  • Levodopa / pharmacology
  • Microscopy, Confocal
  • Models, Animal
  • Neurons / drug effects
  • Neurons / enzymology*
  • Parkinson Disease / enzymology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / deficiency
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Dopamine Agents
  • Serotonin
  • Levodopa
  • Tyrosine 3-Monooxygenase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine