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Volume 17, Number 17, Issue of September 1, 1997 pp. 6761-6768
Copyright ©1997 Society for Neuroscience

Dopaminergic Neurons Intrinsic to the Primate Striatum

Received April 21, 1997; revised June 4, 1997; accepted June 11, 1997.

Ranjita Betarbet1, Robert Turner.1, Vijay Chockkan1, Mahlon R. DeLong1, Kelly A. Allers2, Judith Walters3, Allan I. Levey1, and J. Timothy Greenamyre1, 4, 5

1 Department of Neurology, 2 Graduate Program in Neuroscience, 4 Department of Pharmacology, and the 5 Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322, and the 3 Laboratory of the National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1406

Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-i) cells have received little consideration. In this study we have characterized these neurons and their regulatory response to nigrostriatal dopaminergic deafferentation. TH-i cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys; TH-i cell counts, however, were 3.5-fold higher in the striatum of MPTP-lesioned monkeys. To establish the dopaminergic nature of the TH-i cells, sections were double-labeled with antibodies to dopamine transporter (DAT). Immunofluorescence studies demonstrated that nearly all TH-i cells were double-labeled with DAT, suggesting that they contain the machinery to be functional dopaminergic neurons. Two types of TH-i cells were identified in the striatum: small, aspiny, bipolar cells with varicose dendrites and larger spiny, multipolar cells. The aspiny cells, which were more prevalent, corresponded morphologically to the GABAergic interneurons of the striatum. Double-label immunofluorescence studies using antibodies to TH and glutamate decarboxylase (GAD67), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD67-positive. Very few (<1%) of the TH-i cells, however, were immunoreactive for the calcium-binding proteins calbindin and parvalbumin. In summary, these results demonstrate that the dopaminergic cell population of the striatum responds to dopamine denervation by increasing in number, apparently to compensate for loss of extrinsic dopaminergic innervation. Moreover, this population of cells corresponds largely with the intrinsic GABAergic cells of the striatum. This study also suggests that the adult primate striatum does retain some intrinsic capacity to compensate for dopaminergic cell loss.

Key words: striatum; dopaminergic cells; Parkinson's disease-treated monkeys; dopamine transporter; glutamic acid decarboxylase; calbindin; parvalbumin




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