Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine (DA) levels in the various brain regions of epileptic mice (El mice) were compared immunohistochemically with those in ddY mice (the mother strain of El mice) using a fluorescence microphotometry system. The fluorescence intensities of DA in the neostriatum and nucleus accumbens septi in El mice were approximately 11-15% (P less than 0.01) and 13% (P less than 0.01) lower than in ddY mice. On the other hand, the lower DA amounts in these regions of El mice were improved by intraventricular administration of CaCl2 (10 mumol/kg). The brain regions in which the amount of DA was increased by calcium were areas where high levels of calmodulin and tyrosine hydroxylase are distributed. This finding reconfirmed our previous report that the biogenic amine level disorder in El mice was related to a calcium ion level disorder through a central calcium-calmodulin-dependent biogenic amine-synthesizing mechanism, and this might increase their susceptibility to epileptic convulsions.
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PMID:Effect of intraventricular administration of calcium on the lowering of brain dopamine level in epileptic mice. 227 43

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.
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PMID:[Studies on monoamine metabolism in the rat brain with overdosage of manganese]. 240 98

Immunohistochemical double-labellings of luteinizing hormone-releasing hormone and neuropeptide Y, serotonin, tyrosine hydroxylase and dopamine-beta-hydroxylase, were performed in the preoptic area at the level of the organum vasculosum laminae terminalis. The observed neuropeptide Y-, serotonin-, tyrosine hydroxylase- and dopamine-beta-hydroxylase-immunoreactive fibres presented large varicosities when they were found within close proximity to luteinizing hormone-releasing hormone-containing perikarya. The fact that neuropeptide Y- and dopamine-beta-hydroxylase-immunoreactive fibres exhibited the same morphological characteristics and the comparison of the distribution of these two fibre populations raised the possibility of the co-localization of neuropeptide Y and dopamine-beta-hydroxylase in the same fibres. Dopamine-beta-hydroxylase- and tyrosine hydroxylase-immunoreactive fibres were morphologically different, suggesting that both dopaminergic and noradrenergic fibres could contact luteinizing hormone-releasing hormone-containing perikarya. Serotonin-immunoreactive fibres were also found close to the perikarya and to the proximal dendrite of the luteinizing hormone-releasing hormone-containing neurons. This study showed only putative sites of interactions between chemically identified fibres and luteinizing hormone-releasing hormone-containing neurons. Further ultrastructural immunocytochemical investigations are needed to ascertain the existence of synaptic contacts.
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PMID:Anatomical relationships of monoaminergic and neuropeptide Y-containing fibres with luteinizing hormone-releasing hormone systems in the preoptic area of the sheep brain: immunohistochemical studies. 248 49

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals.
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PMID:Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment. 256 5

Dopamine (DA)-containing cells of the medial basal hypothalamus (MBH) were dissociated and maintained in culture for up to 9 days. Cultures were evaluated both biochemically and immunochemically for DA activity. DA biosynthesis was determined using incorporation of [3H]tyrosine and was analyzed by HPLC with electrochemical detection. Immunochemical studies were performed to identify tyrosine hydroxylase (TH)-positive and neuron-specific enolase (NSE)-positive cells. Morphometric analyses determined the cell size, density, process length and the percent of neurons which were catecholaminergic. TH-positive neurons ranged from 6 to 8% of the total neuronal population when examined over days 3-9 of culture and the length of TH-positive neurites was significantly greater than that of NSE-positive cells. There was incorporation of [3H]tyrosine into DA as evidenced by the presence of [3H]DA in both the media and tissue and the inhibition of synthesis with alpha-methyl-p-tyrosine. There was a greater amount of labeled DA in the media than in the tissue at every time point examined. On the other hand, biosynthesis of DA in fresh brain tissue revealed approximately equal levels of DA in the media and tissue. These studies indicate that DA continues to be synthesized in dissociated cultures of MBH as evidenced by both the biochemical and immunochemical analyses and that there appears to be some alteration in the ability of these neurons to store the newly synthesized amine.
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PMID:An immunochemical and biochemical study of catecholaminergic activity in dissociated hypothalamic cultures. 256 5

Dopamine (DA)-containing projections to the cerebral cortex are considered to play an important role in cognitive processes. Using a recently developed monoclonal antiserum directed against DA and an antibody directed against tyrosine hydroxylase in combination with Golgi impregnation and electron microscopy, we have observed that DA and tyrosine hydroxylase afferents establish symmetric membrane specializations with the soma, dendritic shafts, and spines of identified pyramidal cells in the prefrontal, cingulate, and motor cortex of primates. The axospinous contacts invariably formed part of a synaptic complex in which the dendritic spine of a pyramidal neuron was the target of both a DA-positive symmetric and an unlabeled asymmetric bouton. This arrangement allows direct DA modulation of the overall excitability of cortical projection neurons by altering local spine responses to excitatory inputs.
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PMID:Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. 257 73

In squirrel monkeys (n = 13), 20 mg/kg/day of TIQ was injected subcutaneously for 43 to 104 days. Behavioral scores of motor disturbance were analysed; ranging from 20/45 to 30/45 (mean 27.8 +/- 4.18). Dopamine, total biopterine and tyrosine hydroxylase (TH) were decreased in the substantia nigra of TIQ treated monkeys compared to saline treated monkeys (n = 5). Levodopa was administered in 5 TIQ treated monkeys and remarkable recovery was recorded in these monkeys for more than 2.5 hours. In mice 50 mg/kg/day of TIQ was similarly administered for 70 days. TH staining was negative in about half of the cells of the substantia nigra, but cell bodies were preserved intact when checked by cresyl violet staining. Importance of use of aged animals was indicated in this kind of study.
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PMID:[Tetrahydroisoquinoline and parkinsonism]. 263 Jan 45

The distribution of dopamine-containing cell bodies and fibers was studied with aid of specific antibodies against dopamine in the highly developed brain of the weakly electric fish Gnathonemus petersii. In the telencephalon, dopamine-containing cell bodies were observed in a small area, i.e., area ventralis pars dorsalis and supracommissuralis. In the diencephalon, moderate numbers of dispersed dopamine-immunoreactive cells were present in the preoptic region, while large numbers of dopamine-containing neurons occurred in the hypothalamic paraventricular organ and neighbouring regions. The paraventricular organ, located around small (anterior, intermediate, and posterior) recesses contained many dopamine-immunoreactive cerebrospinal fluid-(CSF)-contacting neurons. Dopamine-containing cells were also observed in a magnocellular hypothalamic cell group, in the nucleus of the lateral recess, and in the nucleus posterior tuberis. In the mesencephalon only a few dopamine-containing cells were observed in a dorsal tegmental (possibly pretectal) area, whereas in ventral mesencephalic regions dopamine-containing cells were lacking. More caudally, dopamine-containing cells were observed in the presumed locus coeruleus, in the caudal region of the reticular formation, and in the presumed area postrema. Dopamine-immunoreactive fiber density was very high in the medioventral hypothalamus and in the preoptic region, where a dense subependymal plexus was observed along the preoptic recess. Such a plexus was also present in the caudal rhombencephalon, where it probably arises from the area postrema. Moderate numbers of dopamine-immunoreactive fibers were present in medioventral parts of the brain along its total rostrocaudal extent as well as in several subnuclei of the torus semicircularis, in the tectum mesencephali, and in the medial part of the dorsal telencephalic area. Other parts of the dorsal telencephalic area, as well as the large cerebellum and the electrosensory lateral line lobe of Gnathonemus, did not contain detectable amounts of dopamine. In spite of the high differentiation of the brain of Gnathonemus, the distribution of catecholamines as visualized with dopamine immunohistochemistry appears to be basically similar to that described in other teleostean and actinopterygian fishes on the basis of formaldehyde-induced fluorescence or tyrosine hydroxylase immunohistochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Distribution of dopamine immunoreactivity in the brain of the mormyrid teleost Gnathonemus petersii. 270 53

Flow cytometry has been revealed as a powerful technique for studying cell populations. The availability of the method to identify, analyze and isolate specific populations of central nervous system cells will be of great aid for studying the in vivo (i.e. neural transplants) and in vitro (i.e. cell cultures) behavior of these cells. The present report describes the analysis and cell sorting of a population of retrogradely fluorescence-labeled dopamine-containing neurons from ventral mesencephalon. Dopamine neurons were identified by immunohistochemical localization of neuron-specific enolase and tyrosine hydroxylase. After being maintained in culture, this relatively pure population differentiates toward a mature phenotype bearing a prominent neuropil.
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PMID:Selective flow cytometric sorting of viable dopamine neurons. 273 Oct 38

During pre- and postnatal development the dopamine-containing nigrostriatal afferents of the striatum are arranged as a conspicuous series of patches (the "dopamine islands"). The development of this dopamine island system, which metamorphoses in early postnatal life to the striosomal architecture of the adult, has recently received considerable attention, but the factors initiating and influencing maturation of this architecture are largely unknown. In an attempt to clarify the relationships between the onset of clustering of dopamine-containing afferents, the grouping of neurons within future striosomes and the maturation of synapses in the striatum, we compared the initial prenatal appearance and subsequent development of immunohistochemical markers for the dopamine-containing innervation [tyrosine hydroxylase (TH)-like immunoreactivity], for synaptic vesicles (SV48-like immunoreactivity), and for a phosphorylation-related enzyme Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II-like immunoreactivity) that is expressed in virtually all striatal neurons by adulthood. Here we present evidence that during striatal ontogeny, both neurons and neuropil expressing CaM kinase II-like immunoreactivity and SV48-positive terminals form discrete patches that are in register with dopamine islands. It is CaM kinase II-positive elements, however, rather than the TH-positive island fibers (or SV48-positive synapses), that initially form overt clusters. Dopamine-containing fibers begin to innervate the striatal anlage just prior to embryonic day (E) 32. Their distribution follows the general lateral to medial developmental gradient characteristic of the striatum but is not yet distinctly islandic. At this time, CaM kinase II-like immunoreactivity was very weak or not present at all and SV48-like immunoreactivity was undetectable. By E36, CaM kinase II-positive neurons are visible in discrete patches of immunopositive neuropil, but only faint inhomogeneities are detectable in the distribution of TH-positive fibers and scarcely any SV48-like immunoreactivity can be seen. By E45, all 3 markers are focused in typical islandic patterns, and they remain so into the early postnatal period. These observations suggest a developmental sequence in which dopamine-containing fibers invade the striatal anlage prior to forming distinct islandic foci and prior to the maturational events signaled by the production of CaM kinase II within the neurons and neuropil of future striosomes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of calcium/calmodulin-dependent protein kinase in relation to dopamine islands and synaptic maturation in the cat striatum. 284 20


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