Primate neostriatal neurons containing tyrosine hydroxylase: Immunohistochemical evidence

Dubach, Mark; Schmidt, Richard H.; Kunkel, Dennis D.; Bowden, Douglas M.; Martin, R. F.; German, Dwight C.

doi:10.1016/0304-3940(87)90298-9

Cited by 153 publications

(97 citation statements)

References 12 publications

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“…In putamen, neuromelanin is likely synthesized within a particular type of neurons expressing tyrosine hydroxylase, the key enzyme for DOPA synthesis. These neurons are present in human and non-human primates and contain a high amount of DOPA; here, the precursor of neuromelanin synthesis is indeed Cys-DOPA (20,21). In brain cortex, the presence of neurons containing tyrosine hydroxylase able to synthesize DOPA was also reported, and this is in agreement with our finding that DOPA is the precursor of neuromelanin identified in this region (22).…”

Section: Discussionsupporting

confidence: 91%

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

Zecca

Bellei²,

Costi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

211

355

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Neuronal pigments of melanic type were identified in the putamen, cortex, cerebellum, and other major regions of human brain. These pigments consist of granules 30 nm in size, contained in organelles together with lipid droplets, and they accumulate in aging, reaching concentrations as high as 1.5-2.6 g/mg tissue in major brain regions. These pigments, which we term neuromelanins, contain melanic, lipid, and peptide components. The melanic component is aromatic in structure, contains a stable free radical, and is synthesized from the precursor molecule cysteinyl-3,4-dihydroxyphenylalanine. This contrasts with neuromelanin of the substantia nigra, where the melanic precursor is cysteinyl-dopamine. These neuronal pigments have some structural similarities to the melanin found in skin. The precursors of lipid components of the neuromelanins are the polyunsaturated lipids present in the surrounding organelles. The synthesis of neuromelanins in the various regions of the human brain is an important protective process because the melanic component is generated through the removal of reactive/toxic quinones that would otherwise cause neurotoxicity. Furthermore, the resulting melanic component serves an additional protective role through its ability to chelate and accumulate metals, including environmentally toxic metals such as mercury and lead.lipids ͉ neuromelanin ͉ brain aging ͉ neurodegenerative

show abstract

Section: Discussionsupporting

confidence: 91%

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

Zecca

Bellei²,

Costi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

211

355

View full text Add to dashboard Cite

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“…The presence of intrinsic TH-positive cells in the striatum is not widely recognized despite two previous reports (Dubach et al, 1987;Tashiro et al, 1989). The reason why these neurons have not been studied in detail may be related to the widespread belief that dopaminergic innervation of the striatum is exclusively extrinsic.…”

Section: Discussionmentioning

confidence: 86%

“…These differ from GABAergic interneurons in that they have fusiform cell bodies and fewer dendritic branches (Gerfen and Wilson, 1996). In contrast to the well-characterized interneuron subtypes, another group of cells immunoreactive for tyrosine hydroxylase (TH-i) exists in the striatum, which have been described by Dubach et al (1987) in nonhuman primates and by Tashiro et al (1989) in rats. Apart from these initial descriptions, little consideration has been given to TH-i striatal cells in the adult striatum.…”

Section: Abstract: Striatum; Dopaminergic Cells; Parkinson's Diseasementioning

confidence: 99%

Dopaminergic Neurons Intrinsic to the Primate Striatum

Betarbet¹,

Turner²,

Chockkan³

et al. 1997

J. Neurosci.

241

198

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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 MPTPlesioned 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. Doublelabel immunofluorescence studies using antibodies to TH and glutamate decarboxylase (GAD 67 ), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD 67 -positive. Very few (Ͻ1%) 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.

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“…As a result, the dopaminergic neuronlike cells found in the striatum may not truly have originated from the grafted MSC-DP cells. However, this is unlikely because the striatum in primates has only a few dopaminergic neurons under normal circumstances: TH + cells number <1% of striatal neurons (53) and are preferentially scattered near the white matter-ventral striatum border. In our case, the TH + /DAT + /GIRK2 + cells were located only in an area near the engrafted area in the dorsal striatum ( Figure 5), and the number of the cells was larger than that in sham and nonaffected striata ( Figure 6, C and E).…”

Section: Figurementioning

confidence: 99%

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

et al. 2012

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Primate neostriatal neurons containing tyrosine hydroxylase: Immunohistochemical evidence

Cited by 153 publications

References 12 publications

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

Dopaminergic Neurons Intrinsic to the Primate Striatum

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

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