Neurochemical characterization of dopaminergic neurons in human striatum

Parkinsonism Relat Disord. 2005 Aug;11(5):277-86. doi: 10.1016/j.parkreldis.2005.02.008.

Abstract

We examined the neurochemical phenotype of striatal neurons expressing tyrosine hydroxylase (TH) mRNA to determine if they form a distinct class of neurons within the human striatum. Double in situ hybridization (ISH) and immunohistochemical (IHC) procedures were used to know if TH mRNA-positive striatal neurons express molecular markers of mature neurons (MAP2 and NeuN), dopaminergic neurons (DAT and Nurr1) or immature neurons (TuJ1). All TH mRNA-labeled neurons were found to express NeuN, DAT and Nurr1, whereas about 80% of them exhibited MAP2, confirming their neuronal and dopaminergic nature. Only about 30% of TH mRNA-labeled neurons expressed TuJ1, suggesting that this ectopic dopaminergic neuronal population is principally composed of mature neurons. The same double ISH/IHC approach was then used to know if these dopamine neurons display markers of well-established classes of striatal projection neurons (GAD65 and calbindin) or local circuit neurons (GAD65, calretinin, somatostatin and parvalbumin). Virtually all TH-labeled neurons expressed GAD65 mRNA, about 30% of them exhibited calretinin, but none stained for the other striatal neuron markers. These results suggest that the majority of TH-positive neurons intrinsic to the human striatum belong to a distinct subpopulation of striatal interneurons characterized by their ability to produce dopamine and GABA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Calbindin 2
  • Corpus Striatum / cytology*
  • Corpus Striatum / physiology*
  • DNA-Binding Proteins / genetics
  • Dopamine / physiology*
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Interneurons / physiology*
  • Isoenzymes / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Transport Proteins / genetics
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Neural Pathways
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Parvalbumins / metabolism
  • Phenotype
  • RNA, Messenger / analysis
  • S100 Calcium Binding Protein G / metabolism
  • Somatostatin / metabolism
  • Transcription Factors / genetics
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Biomarkers
  • CALB2 protein, human
  • Calbindin 2
  • DNA-Binding Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Isoenzymes
  • MAP2 protein, human
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Microtubule-Associated Proteins
  • NR4A2 protein, human
  • Nerve Tissue Proteins
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Parvalbumins
  • RNA, Messenger
  • S100 Calcium Binding Protein G
  • SLC6A3 protein, human
  • Transcription Factors
  • Somatostatin
  • Tyrosine 3-Monooxygenase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
  • Dopamine