Identification of l-DOPA immunoreactivity in some neurons in the human mesencephalic region: a novel DOPA neuron group?

Komori, Kaoru; Uesaka, S.; Yamaoka, H.; Fujita, Kazuo; Yamaoka, K; Naitoh, Hiroshi; Kuroda, Minpei; Karasawa, Nobuyuki; Ito, T.; Kasahara, Yoriko; Nagatsu, Ikuko

doi:10.1016/0304-3940(93)90631-t

Cited by 25 publications

(9 citation statements)

References 14 publications

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“…The idea that L-DOPA acts as a neurotransmitter is supported by several reports concerning the existence of L-DOPA neurons (L-DOPA-positive/ DA-negative) in the rat (8,9), cat (lo), and human brain (11). Such neurons appear to produce L-DOPA as their end-product.…”

Section: Neurotransmitter Character Of L-dopamentioning

confidence: 94%

L‐Dihydroxyphenylalanine and its decarboxylase: New ideas on their neuroregulatory roles

Opacka‐Juffry

Brooks

1995

Movement Disorders

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Recent experimental reports concerning L-dihydroxyphenylalanine (L-DOPA) and aromatic L-amino acid decarboxylase (AADC, L-DOPA decarboxylase) are reviewed in this article. Both in vitro and in vivo data now suggest that L-DOPA is an endogenous neuroactive compound that is released from neurons and acts as a neurotransmitter or neuromodulator in the brain. Administration of exogenous L-DOPA affects dopamine receptor status, AADC activity, and mitochondrial oxidation in experimental animals. The type and severity of these effects depend on the duration of the treatment. These findings may partly explain the limited efficacy of L-DOPA therapy in Parkinson's disease (PD). AADC also plays a controlling role in the central nervous system, being a regulatory enzyme in the synthesis of a putative neuromodulator 2-phenylethylamine and other trace amines. Recent experimental findings on AADC activity and localisation are of importance because they suggest that striatal [18F]DOPA uptake used as an indicator of PD progression in positron emission tomography (PET) studies is likely to overestimate nigrostriatal integrity in advanced PD. Possible new PET tracers of presynaptic dopaminergic function are discussed in this context.

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Section: Neurotransmitter Character Of L-dopamentioning

confidence: 94%

L‐Dihydroxyphenylalanine and its decarboxylase: New ideas on their neuroregulatory roles

Opacka‐Juffry

Brooks

1995

Movement Disorders

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“…However, Panagopoulos et al (1991) did not find dopamine-immunoreactive Purkinje cells in rat cerebellum although they did observe dopaminergic fibers. L-DOPA has more recently been ascribed a potential neurotransmitter role in several regions of the central nervous system Okamura et al, 1988;Meister et al, 1988;Komori et al, 1991Komori et al, , 1993. Additional support for the production of L-DOPA comes from the observation in leaner and tottering mutant mice that Purkinje cells do not immunolabel for aromatic amino acid decarboxylase, the enzyme responsible for the conversion of L-DOPA to dopamine (Hess and Wilson, 1991).…”

Section: Th-immunoreactive Purkinje Cellsmentioning

confidence: 95%

Distribution of tyrosine hydroxylase-immunoreactive afferents to the cerebellum differs between species

1997

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The indirect antibody peroxidase-antiperoxidase technique was used to determine the laminar and lobular distribution of catecholaminergic afferents in the adult mouse, opossum, and cat cerebellum. A monoclonal antibody to tyrosine hydroxylase (TH) revealed a plexus of thin varicose fibers that exhibited a different density and distribution pattern for each species. In the cat, TH-immunoreactive fibers were sparsely distributed to all laminae, lobules, and nuclei of the cat cerebellum except for an area of elevated density in the ventral folia of lobules V and VI. In the opossum, TH-positive fibers were uniformly and densely distributed in the granule and Purkinje cell layers; they were more abundant in vermal lobules V-VI than in more anterior and posterior lobules, particularly I and X. Numerous TH-immunoreactive fibers were found in all four cerebellar nuclei of the opossum. In the mouse, TH-positive fibers formed a dense plexus within all cerebellar lobules, laminae, and nuclei. The mouse also exhibited numerous TH-immunoreactive Purkinje cells that were localized predominantly within vermal lobules VI-X, the paraflocculus, and flocculus. In addition to the interspecies differences in the distribution of catecholaminergic fibers within the cerebellum, comparison of this plexus to that previously described for serotonin in these species reveals that the relative densities and distribution patterns of catecholaminergic and serotoninergic fibers also vary between species. It is thus hypothesized that in each species a given monoamine has a unique net effect on cerebellar output that is determined by its effects on different neuronal populations within the cerebellum.

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“…However, there is accumulating evidence that L-DOPA may itself act as a neurotransmitter or neuromodulator in the central nervous system (CNS). First, the presence in the rat and cat brain of L-DOPA immunoreactive neurons devoid of dopamine immunoreactivity suggests that there are neurons that contain L-DOPA as the end product (Komori et al, 1993). Secondly, recent investigations suggest that L-DOPA can be released from dopaminergic nerve terminals in a neurotransmitter-like fashion and modulate dopamin-ergic and noradrenergic neurotransmission (Misu and Goshima, 1993).…”

Section: Introductionmentioning

confidence: 98%

L-DOPA modulates striatal dopaminergic function in vivo: Evidence from PET investigations in nonhuman primates

Tedroff

Torstenson

Hartvig

et al. 1997

Synapse

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Significant increases in striatal L-[11C]DOPA retention were observed in adult female rhesus monkeys with positron emission tomography (PET) following administration of drugs that increase cerebral L-DOPA concentrations. The monkeys were scanned twice: at baseline (using 10-50 micrograms of tracer substance) and during continuous administration of L-DOPA (3 or 15 mg/kg/h) and 6-R-Erythro-4,5,6,7-tetrahydrobiopterin (6R-BH4) (5 mg/kg/h) and during combined administration of both drugs. PET scans of L-[11C]DOPA distribution were obtained in GE2048-15B or GE4096-15WB Plus positron tomographs. In all studies the specific striatal L-[11C]DOPA influx rate increased by an average of 17-20%. These increases were significantly higher than the retest variability obtained with saline infusions under identical experimental conditions. In individual monkeys the magnitude of increase in the striatal L-[11C]DOPA influx rate varied from no effect of the drug infusion to a 45% increase. Taken together, the results of this study demonstrate that L-DOPA in itself can affect dopaminergic neurotransmission in vivo and also adds further evidence that the neuromodulatory effects of the amino acid are predominantly autoreceptor antagonist-like. The findings most likely have importance for the further understanding of the dopaminergic system in neurodegenerative and psychiatric disorders.

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Identification of l-DOPA immunoreactivity in some neurons in the human mesencephalic region: a novel DOPA neuron group?

Cited by 25 publications

References 14 publications

L‐Dihydroxyphenylalanine and its decarboxylase: New ideas on their neuroregulatory roles

L‐Dihydroxyphenylalanine and its decarboxylase: New ideas on their neuroregulatory roles

Distribution of tyrosine hydroxylase-immunoreactive afferents to the cerebellum differs between species

L-DOPA modulates striatal dopaminergic function in vivo: Evidence from PET investigations in nonhuman primates

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