Neurochemical characterization of dopaminergic neurons in human striatum.
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.
Cossette
Martine
M
Laboratoire de Neurobiologie Systémique, Centre de Recherche Université Laval Robert-Giffard, 2601, de la Canardière, Local F-6500, Beauport, Que., Canada G1J 2G3.
Lévesque
Daniel
D
Parent
André
A
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D064032:Calbindin 2; D003342:Corpus Striatum / Q000166:cytology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010320:Parvalbumins / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D015415:Biomarkers; C576764:CALB2 protein, human; D064032:Calbindin 2; D004268:DNA-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007527:Isoenzymes; C489788:MAP2 protein, human; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; C539882:NR4A2 protein, human; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010320:Parvalbumins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C493214:SLC6A3 protein, human; D014157:Transcription Factors; D013004:Somatostatin; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D004298:Dopamine