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)

The organization of the dopaminergic mesostriatal fibers and their patterns of innervation of the basal ganglia in the squirrel monkey (Saimiri sciureus) were studied immunohistochemically with an antiserum raised against tyrosine hydroxylase (TH). Numerous fibers arose from midbrain TH-positive cell bodies of the substantia nigra pars compacta (group A9), the retrorubral area (group A8), and the lateral portion of the ventral tegmental area (group A10). These fibers accumulated dorsomedially to the rostral pole of the substantia nigra where they formed a massive bundle that coursed through the prerubral field and ascended along the laterodorsal aspect of the medial fore-brain bundle in the lateral hypothalamus. Some ventrally located fibers ran throughout the rostrocaudal extent of the lateral preopticohypothalamic area and could be followed up to the olfactory tubercle, whereas other fibers turned laterodorsally to invade the head of the caudate nucleus. At more dorsal levels in the lateral hypothalamus, many fiber fascicles detached themselves from the main bundle and swept laterally to reach the globus pallidus, the putamen, and the amygdala. Several TH-positive fibers coursed along the dorsal surface of the subthalamic nucleus, and some invaded the dorsomedial third of this structure. The remaining portion of the subthalamic nucleus contained relatively few TH-positive elements. In contrast, the globus pallidus received a dense dopaminergic innervation deriving mostly from two fascicles that coursed backward along the two major output pathways of the pallidum: the lenticular fasciculus caudodorsally and the ansa lenticularis rostroventrally. At the pallidal level, the labeled fibres merged within the medullary laminae and arborized profusely in the internal pallidal segment and less abundantly in the external pallidal segment. However, the caudoventral portion of the external pallidum displayed a dense field of TH-positive axonal varicosities. Other fibers ran through the dorsal two-thirds of the external pallidum en route to the putamen. The striatum contained a multitude of thin axonal varicosities among which a few long and varicosed fibers were scattered. These immunoreactive neuronal profiles were rather uniformly distributed along the rostrocaudal extent of the striatum but appeared slightly more numerous in the ventral striatum than in the dorsal striatum. The pattern of distribution of the TH-positive axonal varicosities in the dorsal striatum was markedly heterogeneous: it consisted of typical zones of poor TH immunoreactivity lying within a matrix of dense terminal labeling.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopaminergic innervation of the basal ganglia in the squirrel monkey as revealed by tyrosine hydroxylase immunohistochemistry. 257 13

The present study applied the separated adrenal capsules of rats for wholemount immunocytochemistry and used tyrosine hydroxylase (TH) antibody as a marker for catecholamines. TH-immunoreactive nerve bundles without varicosities and fibers with varicosities were seen to run along or to encircle blood vessels entering the adrenal capsule from the outside, and then to run along a network of blood vessels in the intracapsular region. Also, the TH-immunoreactive nerve bundles and fibers were found to run along blood vessels in the subcapsular region. Some TH-immunoreactive nerve fibers and bundles with varicosities, unassociated with the blood vessels, were seen in the subcapsular region. In this region, TH-immunoreactive nerve fibers with varicosities were often seen to be closely associated with the cortical cells. Some TH-immunoreactive nerve fibers without varicosities were visible within the splanchnic nerve in the subcapsular region. The present study suggests that numerous catecholaminergic nerve fibers are associated with blood vessels forming a network in the superficial region of the rat adrenal gland.
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PMID:Tyrosine-hydroxylase-immunoreactive nerve fibers in the separated capsule of the rat adrenal gland. 257 26

Noradrenergic (NA) sympathetic innervation of the spleen was examined in young adult Sprague-Dawley rats (200-250 g) following surgical removal of the superior mesenteric-celiac ganglia (SM-CG) and/or bilateral transection of the subdiaphragmatic vagus nerve. Sham-operated and unoperated rats served as controls. NA sympathetic innervation of spleens from sham-operated and unoperated controls, and from vagotomized rats, was qualitatively similar, with fibers distributing to the capsule, trabeculae, vasculature, and parenchyma of the white pulp. Complete ganglionic extirpation resulted in almost total denervation of NA fibers in all compartments of the spleen. High-performance liquid chromatography with electrochemical detection (LCEC) for catecholamines (CA) and quantitative morphometry of the density of NA varicosities confirmed these observations. LCEC revealed a greater than 85% depletion of norepinephrine (NE) in the spleen following superior mesenteric-celiac ganglionectomy. Stereological evaluation of NA varicosities with a point counting method revealed a decline of 99% in the volume density of NA terminals that occurred uniformly in all compartments of spleens from ganglionectomized rats. In addition, stereological analysis revealed a loss of total NA varicosities (approximately 31% decrease) in spleens from sham-operated rats. This loss in volume density occurred largely due to a loss in parenchymal fibers (approximately 45% decrease). Bilateral subdiaphragmatic vagotomy blocked the effect on NA innervation produced by the surgical stress of sham operation. Retrograde tracing following injection of either fluorogold or true blue into the spleen, coupled with immunocytochemical localization of tyrosine hydroxylase (TH), demonstrated abundant fluorogold (true blue)-labeled neurons in the SM-CG; many, but not all, of these neurons also were TH-positive. These findings indicate that the SM-CG neurons supply NA innervation to the spleen, providing sympathetic innervation as the second neuron in the classical two-neuron sympathetic chain, and suggest additional non-NA innervation of the spleen as well. This study also suggests that surgical stress of sham operation may alter directly the NA innervation of the spleen, possibly by inducing temporary retraction of NA fibers of the parenchymal compartment, which is likely to reduce the availability of NE for interaction with cells of the immune system that possess adrenoceptors and are present adjacent to NA varicosities in this region.4+ Bilateral vagotomy ameliorated the effects of sham operation on NA innervation; since the vagal nerve does not distribute fibers to the spleen, this effect is likely to occur through altered feedback circuits effecting sympathetic outflow, or through altered neuroendocrine outflow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Origin of noradrenergic innervation of the spleen in rats. 257 9

The possible relationships between adrenaline-synthesizing neurons and serotoninergic afferent fibers in the nucleus tractus solitarii of the rat were investigated both morphologically and biochemically. Adrenergic elements (cell bodies, dendrites and nerve endings) were detected simultaneously with serotoninergic axonal varicosities in the same electron-microscopic sections by means of combined phenylethanolamine-N-methyltransferase immunocytochemistry and [3H]serotonin-uptake radioautography. Among some 500 serotoninergic varicosities scanned in the areas of significant overlap between the 2 types of labeling, only 3 were directly apposed to an adrenergic process, identified as a dendrite in each case. No synaptic membrane differentiations were seen at these occasional sites of contact. Destruction of the serotonin input by 5,7-dihydroxytryptamine had no significant effect on the tyrosine hydroxylase dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase enzymatic activities in the C2 adrenergic region, but induced 22% and 38% increases of tyrosine hydroxylase and dopamine-beta-hydroxylase activities, respectively, in the neighboring A2 noradrenergic area. Taken together, these results suggest that serotoninergic and adrenergic neurons do not significantly interact in the nucleus tractus solitarii; this implies that the possible catecholaminergic relays for the action of serotonin in autonomic regulation at this level could consist of noradrenergic neurons rather than of their adrenergic counterparts.
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PMID:Are adrenergic neurons subject to a serotoninergic influence in the nucleus tractus solitarii? A morphological and biochemical study in the rat. 257 57

Hypothalamic neurons were grown as single cells in three-dimensional culture. Solitary neurons lacking cell contacts were immunocytochemically examined for inherent expression of vasopressin (VP), tyrosine hydroxylase (TH), and luteinizing hormone releasing hormone (LHRH). Immunoreactive VP and TH were detected within a day. Sixty to eighty-five percent of neurons displayed homogeneously distributed reaction product for VP or TH. One percent exhibited intense punctate staining of somas and varicosities. Few neurons stained for LHRH. Results indicate that hypothalamic neurons can express appropriate neuropeptides and transmitter-specific products without contacting other neurons or nonneuronal cells. Thus, this culture system may provide a useful model to study intrinsic neuronal processes.
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PMID:Solitary hypothalamic neurons inherently express vasopressin and tyrosine hydroxylase. 257 27

In the mouse, monosodium glutamate (MSG) administered neonatally provokes the necrosis of most dopaminergic perikarya in the arcuate nucleus, as classically described, but also stimulates surviving neurons as shown by their increase in both size and immunoreactivity for tyrosine hydroxylase (TH). In the treated animals, TH-immunoreactive axons rarefy in the median eminence (ME) external zone, but postnatal dopaminergic innervation of the intermediate lobe (IL) normally develops and even, due to enlarged axonal varicosities, is more conspicuous than in the control littermate IL at same stages. gamma-Aminobutyric acid-ergic (GABAergic) projections in the ME and the IL, revealed with a glutamic acid decarboxylase antiserum, have the same distribution as TH-immunoreactive axons and present the same modifications in the MSG-treated animals. No clearcut differences in dopaminergic and GABAergic innervation patterns can be observed in the IL in treated and control adult mice.
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PMID:Opposite effects of monosodium glutamate on the dopaminergic and GABAergic innervations of the median eminence and the intermediate lobe in the mouse. 286 9

This study examines the effect of chronic administration of misonidazole on four neurotransmitter pathways (norepinephrine, dopamine, acetylcholine, and GABA) of the central nervous system (CNS). Biochemical assays examined the neurotransmitter synthesizing enzymes tyrosine hydroxylase (TOH) for catecholamines and choline acetyltransferase (CAT) for acetylcholine. An immunocytochemical stain for glutamic acid decarboxylase (GAD) was used as an enzymatic marker for GABAergic neurons. In drug-treated mice, enzymatic activity for TOH as well as the total concentration of enzyme was significantly increased in the locus coeruleus (LC), a principal norepinephrine-containing nucleus of the brainstem, but not in other brain regions. Correlative histofluorescence examination of the LC also showed an increase in the fluorescence intensity of noradrenergic neurons of the nucleus. In contrast, CAT activity was not different from controls in any of the areas examined. In the brainstem, immunocytochemical staining for GAD showed a significant reduction in the number of immunoreactive varicosities juxtaposed to neurons of the lateral vestibular nucleus suggestive of a loss of afferent GABAergic input from the cerebellum. These data suggest that both norepinephrine and GABAergic systems may be altered in selective nuclei of the CNS by chronic administration of misonidazole, and that drug related changes in NE and GABA may underline some of the neurotoxic side effects of MISO and/or exacerbate a patient's pre-existing cardiovascular or neurological problems.
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PMID:Effect of misonidazole on neurotransmitter systems. 287 48

We studied the effect of destruction of the adrenergic neuronal population on the recovery of preganglionic choline acetyltransferase activity in adult rat sympathetic ganglia. To produce a partial destruction of the adrenergic system, rats were injected with guanethidine for 4 weeks; the preganglionic nerve to the superior cervical ganglion was then crushed and the guanethidine injections were continued for an additional 3 days to 6 weeks. To determine that the drug was effective, tyrosine hydroxylase activity was assessed; enzymic activity was reduced by 76% or more after guanethidine administration. In addition, electron microscopy studies showed that the number of principal cell-synaptic contacts and vesicle-containing varicosities were decreased by 90% after guanethidine administration. Those measures indicated the drug effectively destroyed the postsynaptic adrenergic neurons. In contrast, crushing the preganglionic nerve in animals not treated with guanethidine did not change tyrosine hydroxylase activity, suggesting minimal nonspecific damage to the ganglion as a result of the lesion. Choline acetyltransferase activity was measured as an index of presynaptic cholinergic integrity. After crush of the preganglionic nerve, there was a gradual recovery of ganglionic choline acetyltransferase activity in the saline-injected rats from 5% of control 3 days after the crush to 49% of control after 6 weeks. On the other hand, in the ganglia of rats administered guanethidine, there was a much enhanced recovery of choline acetyltransferase activity after the nerve crush compared with saline-injected animals; in the guanethidine-injected rats, the ganglionic choline acetyltransferase activity 3 days and 6 weeks after the nerve crush was 15 and 96%, respectively, compared with the uncrushed side. These results demonstrate after destruction of the adrenergic target tissue, recovery of presynaptic choline acetyltransferase activity in the adult rat sympathetic ganglion can still occur after denervation; however, the mechanism(s) that controls the regeneration is altered, so that enzymic activity is enhanced.
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PMID:Target organ destruction enhances recovery of choline acetyltransferase activity in adult rat sympathetic ganglia after denervation. 287 22

The distribution of serotonin (5-HT) and tyrosine hydroxylase (TH) was examined in the hypothalamus of juvenile baboons, 24 h after infundibular stalk section. Simultaneous immunostaining for 5-HT with peroxidase-antiperoxidase (PAP) and TH with 15 nm colloidal gold (IGS) was performed on Vibratome sections from 3 operated and 1 control female. Light microscopy revealed fine 5-HT immunopositive (5-HT+) fibers, presumably axons, in the suprachiasmatic nuclei and ventromedial hypothalamus (VMH) after stalk section. In addition, focal accumulations of swollen and heavily stained 5-HT+ fibers occurred on the side of the surgical approach. Enlarged fibers were densest in the medial preoptic area, lateral and VMH areas, and the median eminence. TH immunoreactivity (TH+) in VMH cell bodies and axons was only slightly increased over that in controls. Electron microscopy of areas of 5-HT+ and TH+ overlap (medial VMH and adjacent periventricular zone) showed that 5-HT+ profiles were mostly unmyelinated axons and irregular varicosities. A few myelinated 5-HT+ axons were also observed. TH+ perikarya, dendrites, axons and terminals showed gold labeling characteristic for this enzyme. However, colocalization of 5-HT (PAP) and TH (IGS) was present in a number of fiber varicosities in experimental animals only. Both single- and double-labeled profiles occurred in individual thin sections, thus arguing against antibody cross-reactivity. These results indicate that: hypothalamic 5-HT+ fibers project to the median eminence in primates; 5-HT fibers become more obvious after stalk section due to accumulation of transmitter; focal 5-HT+ immunoreactivity in the hypothalamus can increase dramatically after distant and mild surgical trauma, and coexistence of 5-HT and TH in single neurons can appear after acute stalk section and/or trauma in experimental animals. These findings might represent uptake of exogenous 5-HT or amplified expression of endogenous neurotransmitter, suggesting that plasticity of transmitter phenotype might follow acute surgical and/or endocrine intervention in mature primate brain. Neuroendocrine studies employing the stalk-sectioned primate might thus be radically affected.
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PMID:Immunostaining reveals accumulation of serotonin and coexistence with tyrosine hydroxylase in hypothalamic neurons of acutely stalk-sectioned baboons. 288 96

Immunocytochemistry was used to demonstrate tyrosine hydroxylase (TH)-positive profiles in the spleen of the adult Fischer 344 rat. At the light microscopic level, numerous varicose nerve profiles were seen in the white pulp, particularly surrounding the central arteries and their arteriole branches. At the electron microscopic level, varicosities were seen in close proximity to smooth muscle cells of the arteries, and directly abutting lymphocytes (presumable T-lymphocytes) of the nearby periarteriolar lymphatic sheath. There were no intervening cell processes between the TH-positive terminals and the lymphocyte. The opposing membranes were smooth and evenly spaced approximately 6 nm apart. Additional TH-positive nerve profiles were seen in the inner marginal zone and within trabeculae. The correlation between this immunocytochemical staining and previously demonstrated histofluorescence for norepinephrine leads to the conclusion that lymphocytes in the splenic white pulp have direct associations with noradrenergic fibers of the sympathetic nervous system. This association provides a route by which the autonomic nervous system could directly influence specific immune system effector cells.
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PMID:Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)-positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp. 289 Jul 71


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