Tyrosine hydroxylase and aromatic l-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex

Ikemoto, Keiko; Kitahama, Kunio; Nishimura, Akiyoshi; Jouvet, Anne; Nishi, Katsuji; Arai, Ryohachi; Jouvet, Michel; Nagatsu, Ikuko

doi:10.1016/s0304-3940(99)00409-7

Cited by 44 publications

(46 citation statements)

References 13 publications

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“…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). In cerebellum, no description of neurons expressing tyrosine hydroxylase is available; however, the synthesis of neuromelanins could take place in neurons having this enzyme, similar to those of putamen and cortex.…”

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.

204

351

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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

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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.

204

351

View full text Add to dashboard Cite

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“…No catecholamine-synthesizing enzymes subsequent to TH, including AADC, have been observed in TH-IR neurons in the developing or adult rodent or primate cortex, calling into question the catecholaminergic status of these cells (Berger et al, 1985;Gaspar et al, 1987;Satoh and Suzuki, 1990;Ikemoto et al, 1999;Weihe et al, 2006). Additionally, in the developing rat, labeling of the cortical TH-IR neurons was insensitive to 6-hydroxydopamine toxicity, and no endogenous catecholamines were detected in cortical somata (Berger et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…These TH cells, however, remain enigmatic because of their species-specific laminar distribution, lack of additional catecholaminergic traits, and developmental characteristics. In the rat cortex, TH-IR neurons were observed mainly in layer II/III (Berger et al, 1985;Kosaka et al, 1987a;1987b), whereas in the mouse (Satoh and Suzuki, 1990) and human (Gaspar et al, 1987;Hornung et al, 1989;Kuljis et al, 1989;Trottier et al, 1989;Ikemoto et al, 1999;Benavides-Piccione and DeFelipe, 2003;Marui et al, 2003;Benavides-Piccione and DeFelipe, 2007), TH-IR neurons were seen predominantly in layers V and VI. Not only are these TH neurons outside the classically-defined catecholaminergic cell groups (Hokfelt et al, 1984), but their final transmitter phenotype is also uncertain.…”

Section: Introductionmentioning

confidence: 95%

“…Not only are these TH neurons outside the classically-defined catecholaminergic cell groups (Hokfelt et al, 1984), but their final transmitter phenotype is also uncertain. In all species examined, cortical TH-IR cells failed to express any catecholaminergic enzymes subsequent to TH, including aromatic amino acid decarboxylase (AADC), which synthesizes dopamine (Berger et al, 1985;Gaspar et al, 1987;Ikemoto et al, 1999;Weihe et al, 2006). Although very few TH-IR cells were noted in the adult rat cortex in classical TH distribution studies (Hokfelt et al, 1984), later reports described a population of cortical TH-IR cells that were observed transiently during postnatal development in the rat (Berger et al, 1985) and mouse (Satoh and Suzuki, 1990).…”

Section: Introductionmentioning

confidence: 98%

“…A subset of cortical neurons also expresses TH in the rodent (Berger et al, 1985;Kosaka et al, 1987a;1987b;Satoh and Suzuki, 1990), non-human primate (Weihe et al, 2006), and human (Gaspar et al, 1987;Hornung et al, 1989;Kuljis et al, 1989;Trottier et al, 1989;Fukuda et al, 1999;Ikemoto et al, 1999;Benavides-Piccione and DeFelipe, 2003;Marui et al, 2003;Benavides-Piccione and DeFelipe, 2007). Based on their size, morphology, and partial colocalization with GABA, cortical TH-IR cells were hypothesized to be interneurons.…”

Section: Introductionmentioning

confidence: 99%

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Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

et al. 2008

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Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical THimmunoreactive neurons were first observed two weeks postnatally and peaked in number three weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggests that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in nonoverlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence.

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Differential expression of catecholamine biosynthetic enzymes in the rat ventrolateral medulla

Phillips

Goodchild

Dubey

et al. 2001

J of Comparative Neurology

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Adrenergic (C1) neurons located in the rostral ventrolateral medulla are considered a key component in the control of arterial blood pressure. Classically, C1 cells have been identified by their immunoreactivity for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and/or phenylethanolamine N-methyltransferase (PNMT). However, no studies have simultaneously demonstrated the expression of aromatic L-amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) in these neurons. We examined the expression and colocalization of all four enzymes in the rat ventrolateral medulla using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Retrograde tracer injected into thoracic spinal segments T2-T4 was used to identify bulbospinal neurons. Using fluorescence and confocal microscopy, most cells of the C1 group were shown to be double or triple labeled with TH, DBH, and PNMT, whereas only 65-78% were immunoreactive for AADC. Cells that lacked detectable immunoreactivity for AADC were located in the rostral C1 region, and approximately 50% were spinally projecting. Some cells in this area lacked DBH immunoreactivity (6.5-8.3%) but were positive for TH and/or PNMT. Small numbers of cells were immunoreactive for only one of the four enzymes. Numerous fibres that were immunoreactive for DBH but not for TH or PNMT were noted in the rostral C1 region. Single-cell RT-PCR analysis conducted on spinally projecting C1 neurons indicated that only 76.5% of cells that contained mRNA for TH, DBH, and PNMT contained detectable message for AADC. These experiments suggest that a proportion of C1 cells may not express all of the enzymes necessary for adrenaline synthesis.

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Tyrosine hydroxylase and aromatic l-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex

Cited by 44 publications

References 13 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

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

Differential expression of catecholamine biosynthetic enzymes in the rat ventrolateral medulla

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