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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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