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)

Questions arising from recent clinical neural transplantation trials in Parkinson's disease have under-scored the necessity for a thorough experimental evaluation of the structural and functional consequences of this procedure. The present study investigated the neuroanatomical host reaction to intrastriatal implants in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated nonhuman primates. Nine monkeys (Cebus apella) received intrastriatal implants using either a stereotactic approach with a silver tissue carrier or an open microsurgical procedure. Seven of these animals received intrastriatal adrenal medullary autografts, while two received control implants consisting of the tissue carrier alone. One month following transplantation, the hosts' brains were evaluated via immunohistochemical and routine histologic methods. In both MPTP-treated and normal monkeys, enhanced ipsilateral expression of tyrosine hydroxylase-like immunoreactive (TH-IR) fibers in the caudate nucleus was observed, despite minimal survival of adrenal chromaffin cells in the implants. The intensity of this response was greatest adjacent to the implant site, but a clearly increased degree of ipsilateral striatal fiber staining also could be seen several millimeters from the graft. TH-IR fibers also were more dense and of thicker caliber throughout the nigrostriatal and mesolimbic pathways ipsilateral to the implant. Control stereotactic implants, consisting of a silver tissue carrier alone, produced a similar enhancement of immunoreactive fibers, suggesting an induction of TH-IR fibers by the parenchymal injury produced during surgical implantation. There are two major hypotheses proposed to explain why adrenal medullary grafts may promote functional recovery in human parkinsonism: (1) replacement of lost striatal neurotransmitter (dopamine) by the viable grafted tissue, or (2) induction of recovery of remaining host dopaminergic systems by the implantation procedure. Our current data appear to support the latter.
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PMID:Adrenal medullary autografts into the basal ganglia of Cebus monkeys: injury-induced regeneration. 290 68

To best interpret the significance of neurological alterations produced by chemicals, the changes in morphological as well as neurochemical parameters must be measured and compared to each other. We have devised an approach to readily label microscopic sections for multiple antigens (neurotransmitters, enzymes, peptides, etc.) as well as for the demonstration of degenerating structures by silver impregnation. Here, we applied silver-staining together with immunolabelling of 5-HT and tyrosine hydroxylase (the rate-limiting enzyme for dopamine synthesis) to study neurohistological alterations produced by methylenedioxymethamphetamine (MDMA), a hallucinogenic stimulant previously used as an adjunct to psychotherapy and now a popular recreational drug ("Ecstasy"). Single oral doses of 40 or 80 mg/kg MDMA doubled the density of silver-impregnated (degenerating) fiber terminals in the caudate nucleus compared to controls, when rats were sacrificed 18 hours after treatment. Four months after two 40 mg/kg oral doses per day for four days, rats had a reduced neurochemical content of 5-HT in the hippocampus, and fewer immunostainable 5-HT axons per unit area in the hippocampal stratum lacunosum but no change in brain-stem neurochemical 5-HT content or in the numeric density of 5-HT-positive cell bodies in the dorsal raphe nucleus. The neurohistology suggests interpreting the changes in neurochemical content of serotonin produced by MDMA as due to degeneration followed by subsequent loss of 5-HT axons, rather than a decrease in the rate of neuronal 5-HT synthesis or a toxicity directed toward 5-HT cell bodies. The combination of neurohistological and neurochemical evaluation will continue to prove useful in comprehensive evaluation of the neurological effects of chemical exposure.
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PMID:Neuropathological evaluation by combined immunohistochemistry and degeneration-specific methods: application to methylenedioxymethamphetamine. 290 68

In two groups of silver foxes--i.e. selected by the domestic type of behaviour and aggressive ones--studies have been made on the activity of the key enzyme in biosynthesis of catecholamines--i.e. tyrosine hydroxylase from the brain. Domesticated animals exhibited higher enzymic activity in the locus coeruleus, hypothalamus and cortex. Animals from both groups did not differ with respect to the level of tyrosine hydroxylase activity in the corpus striatum. The enzymic reactions of homogenates from locus coeruleus region of the brain in both groups of animals, as well as homogenates from the corpus striatum of the brain of aggressive animals exhibited low and approximately equal values of Michaelis constant for tyrosine. The value of KM was 3 times higher in the hypothalamus in both groups of foxes and in the corpus striatum of tame animals. Presumably, selection of silver foxes for the domestic type of behaviour resulted in the increase of biosynthesis of catecholamines in the brain due to the increase in the number of enzyme molecules. The increase in the activity of tyrosine hydroxylase in noradrenaline system of the brain may be associated with changes in the behavioural pattern of animals resulting from selection.
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PMID:[Brain tyrosine hydroxylase activity in behavior-selected silver foxes]. 290 5

Continuous 3-day administration of d-amphetamine sulfate via a subcutaneous minipump induced the appearance of tyrosine hydroxylase immunoreactive patches in the neostriatum of adult Sprague-Dawley and Long-Evans rats at doses (greater than 20 mg/kg/day) that also produced axonal terminal degeneration as evidenced by Fink-Heimer silver grain deposition. The tyrosine hydroxylase patches coincided with striosomes identified by Leu-enkephalin immunoreactivity on adjacent sections. Sham-operated control, naive control, low dose amphetamine- (less than 15 mg/kg/day) and cocaine- (less than 125 mg/kg/day, IV) treated rats did not show tyrosine hydroxylase neostriatal patches nor axonal degeneration. These results suggest that the diffuse neostriatal dopamine system may be more susceptible to the neurotoxic, degenerative action of continuously administered amphetamine than is the islandic dopamine system.
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PMID:Continuous amphetamine administration induces tyrosine hydroxylase immunoreactive patches in the adult rat neostriatum. 290 31

The presence of serotonin (5-HT) in chromaffin cells of the frog adrenal (inter-renal) gland has been demonstrated both by immunocytochemical and biochemical techniques. Using antisera against 5-HT and tyrosine hydroxylase (TH) on consecutive sections, we found by means of the indirect immunofluorescence technique that a majority of chromaffin cells were also immunopositive for 5-HT. When antibodies to 5-HT and phenylethanolamine-N-methyltransferase (PNMT) were applied on consecutive sections, 5-HT-like immunoreactivity was observed in almost all epinephrine-producing cells which represented about 90% of the total chromaffin cells. No 5-HT-containing fibres could be detected. At the ultrastructural level, using a pre-embedding procedure associated with gold-silver intensification of the immunoperoxidase reaction, 5-HT-immunoreactivity was visualized in secretory vesicles essentially located in the periphery of epinephrine cells. Combination of high performance liquid chromatography and electrochemical detection showed the presence of both 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in frog adrenal extracts. Transection of the splanchnic nerve enhanced 5-HT immunoreactivity and augmented the amount of 5-HT in adrenal extracts. Taken together, these results indicate that epinephrine-producing cells of the frog adrenal contain significant amounts of serotonin. The observation of the storage of 5-HT in secretory vesicles of epinephrine cells suggests that serotonin may be released with catecholamines under stress conditions.
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PMID:Immunohistochemical and biochemical evidence for the presence of serotonin in amphibian adrenal chromaffin cells. 316 76

Continuous three day administration via implanted minipumps of cocaine hydrochloride (50-450 mg/kg/day, sc and 100-250 mg/kg/day, iv) did not produce axonal degeneration in frontal agranular cortex or neostriatum that was detectable by Fink-Heimer silver staining or tyrosine hydroxylase immunolabeling. This is in contrast to the extensive axonal degeneration detectable in these regions following d-amphetamine sulfate (10-60 mg/kg/day) administered following an identical protocol. Doses of cocaine and amphetamine were equated using three measures: 1) weight loss, 2) lethality and 3) behavioral activation. Thus, cocaine resembles other catecholamine reuptake blockers and does not cause the neurodegenerative changes characteristic of other abused drugs that interact with the brain's dopamine systems.
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PMID:Cocaine, in contrast to D-amphetamine, does not cause axonal terminal degeneration in neostriatum and agranular frontal cortex of Long-Evans rats. 318

Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliter each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy cholinergic cells which are located within the pedunculopontine tegmental (PPT), laterodorsal tegmental (LDT), parabrachial (PB), and locus ceruleus (LC) nuclei in this species. The neurotoxic lesions resulted in the destruction of the majority (approximately 60%) of choline acetyltransferase (ChAT)-immunoreactive neurons and a minority (approximately 35%) of tyrosine hydroxylase (TH)-immunoreactive neurons, as well as in the destruction of other chemically unidentified neurons, in the region. The effects of these lesions upon the cholinergic innervation of the brain were investigated by comparison of brains with and without lesions which were processed for acetylcholinesterase (AChE) silver, copper thiocholine histochemistry and ChAT radio-immunohistochemistry. In the forebrain, a major and significant decrease in AChE staining, measured by microdensitometry, and associated with a decrease in ChAT immunoreactivity was found in certain thalamic nuclei, including the dorsal lateral geniculate, lateral posterior, pulvinar, intralaminar, mediodorsal and reticular nuclei. All of these nuclei receive a rich cholinergic innervation evident in both AChE histochemistry and ChAT immunohistochemistry. No significant difference in AChE staining or ChAT immunoreactivity was detected in other thalamic nuclei or in the subthalamus, hypothalamus or basal forebrain. In the brainstem, a significant decrease of AChE staining and ChAT immunoreactivity was found in the superior colliculus and the medullary reticular formation, where ChAT-immunoreactive fibers were moderately dense in the normal animal. These results indicate that the pontomesencephalic cholinergic neurons may influence the forebrain by major projections to the thalamus, involving both relay and non-specific thalamocortical projection systems, and thus act as an integral component of the ascending reticular system. They may influence the brainstem by projections onto deep tectal neurons and other reticular neurons, notably those in the medullary reticular formation, and thus also affect bulbar and bulbospinal systems.
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PMID:Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain. 325 79

Mouse tumor C1300 has been established in tissue culture. The cells have a round cell morphology in both the subcutaneous tumor and in suspension culture. However, when given a surface on which to attach, they send out processes up to 3 mm in length and assume the morphology of mature neurons. The attached cells are stained by the Bodian silver procedure for neurons, whereas the cells grown in suspension are not. Electron microscopy reveals that the attached cells contain neurofilaments, neurotubules, and densecore vesicles indicative of nerve fibers. Both free-floating and attached cells have tyrosine hydroxylase activity characteristic of sympathetic nervous tissue. Apparently cell attachment can induce morphological differentiation from an anaplastic round cell to a cell which has many properties of a mature neuron.
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PMID:In vitro differentiation of a mouse neuroblastoma. 418

Combined radioautography and immunocytochemistry were used to define the ultrastructure and synaptic relations between vagal sensory afferents and catecholaminergic (CA) neurons of the A2 group located within the nucleus tractus solitarius (NTS) of rat brain. The vagal afferents were radioautographically labeled by tritiated amino acids anterogradely transported from the nodose ganglion. Immunocytochemical labeling for tyrosine hydroxylase (TH) served for the identification of catecholaminergic neurons. The radiographically labeled axons seen by light microscopy were widely distributed throughout the more caudal NTS. The reduced silver grains were more densely distributed within the NTS located homolateral to the injected nodose ganglion. The radioautographically labeled processes were localized in regions containing catecholaminergic neurons as indicated by immunoreactivity for TH. Electron microscopic analysis of the medial NTS at the level of the obex demonstrated that the reduced silver grains were localized within axon terminals. The radioautographically labeled terminals were 2-3 microns in diameter, contained numerous small, clear and a few large, dense vesicles, and formed predominately axodendritic synapses. Many of the recipient dendrites contained immunoreactivity for TH. In rare instances, vagal afferents formed synaptic appositions with both TH-labeled and unlabeled axon terminals and neuronal soma. This study provides the first ultrastructural evidence that the catecholaminergic neurons within the NTS receive direct synapses from sensory neurons in the nodose ganglion.
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PMID:Synaptic interaction of vagal afferents and catecholaminergic neurons in the rat nucleus tractus solitarius. 613 45

The ultrastructural morphology of serotoninergic terminals and their synaptic relation with catecholaminergic neurons were examined in the medial nuclei of the solitary tracts (m-NTS) using combined autoradiographic and immunocytochemical methods. Adult rats were pretreated with a monoamine oxidase inhibitor and subjected to a 2-hour intraventricular infusion of 50 nM tritiated 5-hydroxytryptamine (3H-5HT). At the termination of the infusion, the brains were fixed by aortic arch perfusion with a mixture of 4% paraformaldehyde and 0.5% glutaraldehyde. Coronal Vibratome sections through the NTS and more rostral raphe nuclei were immunocytochemically labeled with specific antiserum to serotonin or tyrosine hydroxylase and then processed for autoradiography. By light microscopy, concentrations of reduced silver grains indicating uptake of 3H-5HT usually paralleled the localization of peroxidase immunoreactivity for serotonin in neuronal perikarya of the rostral raphe nuclei and in varicosities in the brainstem. The 3H-5HT-containing varicosities were found throughout the medial and commissural portions of the NTS, where they were frequently associated with processes showing immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase. Ultrastructural examination of the m-NTS revealed that the silver grains for 3H-5HT were accumulated over axon terminals. The 5HT-labeled terminals contained a heterogeneous population of vesicles and formed both symmetric and asymmetric synapses with dendrites. The recipient dendrites were either, unlabeled or showed immunoreactivity for tyrosine hydroxylase. These findings support a direct serotoninergic modulation of catecholaminergic neurons within the rat m-NTS.
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PMID:Serotoninergic terminals: ultrastructure and synaptic interaction with catecholamine-containing neurons in the medial nuclei of the solitary tracts. 614 1


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