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)

Mesostriatal projections, which arise from dopaminergic and non-dopaminergic neurons in the ventral tegmental area, substantia nigra, and retrorubral area, are compartmentally organized in the striatum. Anterograde axonal tract tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L), combined with immunohistochemical localization of tyrosine hydroxylase (TH) and autoradiographic localization of mu-opiate receptor binding sites, shows that midbrain projections to the striatum are distributed to either the mu-opiate receptor-rich "patch" or the receptor-poor "matrix" striatal compartments. Three morphologically distinct mesostriatal afferent fiber types are labeled. The first type, type A, forms a plexus of relatively thin (0.1-0.4 micron), smooth fibers with small varicosities (0.3-0.6 micron). A second type, type B, is similar to the first in forming a plexus of fibers, but is slightly thicker (0.2-0.6 micron), with more frequent varicosities (0.4-1.0 micron) that give this fiber type a crinkled appearance. The third type, type C, constitutes a minority of striatal afferents and is characterized by its large caliber (0.4-0.7 micron) with large bulbous varicosities (1.2-2.0 micron). Projections of the ventral tegmental area (A10 cell group) are primarily dopaminergic type A fibers directed to the matrix of the ventromedial striatum, including the nucleus accumbens. The retrorubral area (A8 cell group) also provides predominantly dopaminergic type A fibers to the striatal matrix, but these are distributed dorsally. The substantia nigra contains a mixed population of neurons that project to the striatum. Some, located in the dorsal tier of the pars compacta (dorsal A9 cell group), provide dopaminergic type A fibers to the striatal matrix. Others, in the ventral tier of the pars compacta (ventral A9 cell group) and in the ventral tier of the pars reticulata (displaced A9 cells), provide dopaminergic type B fibers to the striatal patches. An additional set of substantia nigra neurons that are non-dopaminergic is the source of type C fibers to the striatal matrix. Thus, distinct dorsal and ventral sets of midbrain dopaminergic neurons project, respectively, to striatal matrix and patches, and there is a non-dopaminergic mesostriatal projection to the matrix.
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PMID:The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. 289 99

The serotoninergic (5-hydroxytryptamine, 5-HT) innervation of the rat ventral tegmental area (VTA) was examined by light and electron microscopic radioautography following intraventricular infusion of [3H]5-HT. The [3H]5-HT labeled processes were characterized with respect to their regional distribution, ultrastructure and relationships with all neurons, including dopaminergic neurons, identified in the same sections using immunocytochemistry for the localization of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). By light microscopy, [3H]5-HT labeled axons and axonal varicosities were detected throughout the interfascicular nucleus and ventral portion of the VTA. By electron microscopy, [3H]5-HT-labeled axons were found to be mainly small and unmyelinated, although a few showed several lamellae of myelin. The labeled varicosities measured 0.6 micron in mean diameter and contained many small, round or flattened agranular vesicles and a few large granular vesicles. More than 18% showed synaptic specializations in single thin sections. Most of these synapses were asymmetric and established on dendritic shafts. Based on the probability of seeing such synaptic specializations in single thin sections, it was estimated that as many as 50% of the labeled 5-HT terminals formed synaptic contacts in the VTA. In dually labeled light microscopic sections, [3H]5-HT-accumulating processes often appeared adjacent to TH-immunoreactive perikarya and proximal dendrites. Electron microscopy demonstrated that terminals with radioautographic labeling for 5-HT formed conventional synapses both with TH-labeled and unlabeled dendrites in the VTA. Many additional 5-HT terminals lacking recognizable synaptic densities were directly apposed to TH-labeled dendrites and were isolated from the rest of the neuropil by thin glial leaflets. These results suggest that 5-HT neurons innervate both dopaminergic and non-dopaminergic neurons in the VTA and may influence mesocortical and mesolimbic efferent systems through synaptic as well as non-synaptic mechanisms.
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PMID:Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons. 289 80

A combined immunoperoxidase/immunofluorescence procedure was used to examine potential sites of overlap between catecholamine and LHRH systems in the brains of ewes sacrificed during either anestrous or the breeding season. Cells and fibers immunoreactive for either tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase (DBH) were visualized in the same sections as immunopositive LHRH perikarya and fibers. TH- and DBH-positive varicosities in the preoptic area and anterior hypothalamus appeared to contact both LHRH cell bodies and their dendrites. Clusters of TH-positive cells and fibers were found in the organum vasculosum of the lamina terminalis, and partially overlapped the location of immunoreactive LHRH fibers in that structure. Immunoreactive TH and LHRH fibers were densely interspersed within the zona externa of the median eminence, particularly within its lateral portion. No obvious qualitative differences were apparent in either the distribution of catecholamine cells and fibers or their overlap with LHRH elements between the brains of anestrous and breeding season ewes. These observations suggest the possibility of catecholaminergic synaptic inputs onto LHRH neurons in the ewe, as well as the potential for interaction between catecholamines and LHRH at the level of the median eminence.
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PMID:Potential sites of interaction between catecholamines and LHRH in the sheep brain. 289 58

Adrenal medullary cell suspensions, derived from newborn rats (postnatal day 1-6), were implanted into the head of the caudate nucleus in 35 rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopamine (DA) pathway. Behavioral recovery from Met-amphetamine induced circling, cell growth and morphological features (tyrosine hydroxylase positive cells), and release of adrenaline (Ad), noradrenaline (NA), DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated for 40 weeks after transplantation. Met-amphetamine induced circling decreased significantly in 43% (15/35) of the rats. The decrease was concurrent with transmutation of the tyrosine hydroxylase-like immunopositive (THLI) cells into mature neurons that had abundant elongated neurites with varicosities and synapses on neuronal elements in the host caudate. In the absence of behavioral recovery (57%, 20/35) THLI cells were very scant. DA, DOPAC and HVA were reduced more than 90% in perfusates collected by in vivo dialysis from the striata of the animals that were not improved by transplant. These levels recovered to 20-50% of controls in animals whose behavior recovered. Ad and NA were not detected in the perfusates of either recovered or non-recovered animals. The results suggest that some grafted adrenal medullary cells transform into dopaminergic neurons and the release of DA from these grafted cells functionally affects behavior improvement for at least 40 weeks.
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PMID:Adrenal medullary cells transmute into dopaminergic neurons in dopamine-depleted rat caudate and ameliorate motor disturbances. 289 25

Ventral mesencephalic anlagen survive following grafting to the striatum of weaver mutant mice and reinnervate the dopamine-depleted basal ganglia of the recipients. The aim of the present study was to examine the pattern of connectivity established by graft-deriving dopamine afferents in the host striatum. Grafts were obtained from normal embryos at a gestational age of 14-15 days and implanted into a surgical cavity overlying the dorsal striatum of adult weaver recipients. Tissue was processed for electron microscopic immunocytochemistry using a primary antiserum against tyrosine hydroxylase. At the time of examination, recipient weaver mutants were 8.5 months old and the grafts had survived for 4.5 months. Grafts were found to contain an estimated 100-1000 tyrosine hydroxylase immunoreactive neurons. Tyrosine hydroxylase immunoreactive fibres, displaying characteristic varicosities, innervated the dorsal striatum to a depth of 1000 micron. In the non-grafted striatum, 8% of the contacts of tyrosine hydroxylase immunoreactive nerve terminals were junctional. That proportion contrasted with the corresponding value of normal animals, which is 27%. In the grafted striatum, 29% of the contacts were junctional. That percentage approximated the value found in normal animals. By applying a stereological correction, it can be estimated from those numbers that the true proportion of junctional contacts in the non-grafted striatum of 8.5-month-old mutants may be 26%, whereas that in the grafted side may be 91%, which is close to the normal situation. The majority of contacts in the reinnervated striatum (84%) were made with dendrites and spines. However, the proportion of total axosomatic contacts in the reinnervated striatum was twice as high as that found in the striatum of normal animals, and the proportion of junctional synapses was three times higher than that found normally. We conclude that: (1) in spite of a genetically determined degenerative process, the dorsal neostriatum of weaver mutant mice is receptive to synaptic investment by dopamine afferents originating in normal donor tissue. (2) In repopulating the denervated weaver striatum, graft-deriving dopamine afferents display a connectional selectivity, i.e. they establish synaptic relations preferentially with those cellular domains that are normally innervated by dopamine nerve terminals. In this context, it is possible that dopamine fibres originating in the grafts invest postsynaptic sites that had either been vacated from the intrinsic dopamine input or had never received such an input. (3) The striatal connectivity following transplantation may retain features of immaturity as suggested by t
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PMID:Reinstatement of synaptic connectivity in the striatum of weaver mutant mice following transplantation of ventral mesencephalic anlagen. 290 79

Indirect immunofluorescence histochemistry was used to study the relation among GABAergic, catecholaminergic, cholinergic, and peptidergic neurons in the rat mediobasal hypothalamus. By employing a direct double-labelling procedure using sheep antiserum against glutamic acid decarboxylase (GAD), mouse monoclonal and rabbit antibodies to neurotensin (NT) and rabbit antisera to tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), galanin (GAL), growth hormone-releasing factor (GRF), or somatostatin (SOM), it was demonstrated that GAD-positive fibers and terminals in the external part of the median eminence co-contained immunoreactivity for TH, NT, GAL or GRF, but not for SOM. In the internal part of the median eminence-infundibular stalk, GAD-positive/NT-, GAL-, and GRF-negative and GAD-positive/TH-positive fiber plexa were shown. When a recently developed direct triple-labelling procedure with biotin-conjugated mouse secondary antibodies in conjunction with diethylaminocoumarin (DAMC)-conjugated avidin was employed, presence of GAD/GAL/NT- as well as GAD/GRF/NT-containing varicosities could be demonstrated close to hypophysial portal vessels. In colchicine-pretreated animals, GAD was shown to coexist with TH, NT, or GAL in cell bodies in both the dorsomedial and ventrolateral domains of the arcuate nucleus, but with GRF only in the ventrolateral division. ChAT-positive neurons in the ventrolateral region were also TH-positive. In the ventrolateral arcuate nucleus, triple-labelling followed by elution-restaining showed GAD/NT/GAL/TH-immunoreactivities in the same cells. Similarly, double-labelling with two following elution-restaining steps showed several NT/GAL/GRF/TH-containing cell bodies in this part of the arcuate nucleus. GAD-positive cells in the anterior hypothalamic periventricular area and fibers in the pituitary neurointermediate lobe were also TH-positive. The results demonstrate complex patterns of storage of chemical messengers in neurons of the arcuate nucleus-median eminence complex. Possible neuroendocrine interactions of these systems in the control of prolactin and growth hormone secretion are discussed.
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PMID:Peptide- and transmitter-containing neurons in the mediobasal hypothalamus and their relation to GABAergic systems: possible roles in control of prolactin and growth hormone secretion. 290 36

Cellular relationships between serotonin (5-HT) axons and tyrosine hydroxylase (TH)-containing neurons were examined by combined (3H)5-HT uptake radioautography and TH immunocytochemistry in the medial zona incerta (ZI) of adult rats, 7 and 50 days after an intracerebral injection of 5,7-Dihydroxytryptamine (5,7-DHT). Seven days post-lesion, only rare, scattered (3H)5-HT-labeled axon terminals were apparent in the zone of the medial ZI accessible to intraventricularly injected (3H)5-HT. In contrast, in sham-injected animals (3H)5-HT-labeled varicosities were numerous and often observed adjacent to TH-immunoreactive perikarya and dendrites. Fifty days post 5,7-DHT injection, the density of (3H)5-HT-labeled terminals approximated that seen in sham-treated animals. At the ultrastructural level, these regenerated 5-HT axons were similar in size, shape and content to those observed in sham-operated rats. Also, as in sham, some of the (3H)5-HT-labeled axons were directly apposed to TH-immunopositive labeled profiles. The latter included large dendritic shafts and dendritic spines, but only rare perikarya. In both sham- and 5,7-DHT-treated animals a few of the contacts between (3H)5-HT-labeled and TH-immunoreactive profiles exhibited an asymmetric synaptic differentiation. These results indicate that 5-HT fibers in the medial ZI, following regeneration, can reestablish normal relationships and even synapses with a given population of chemically identified cells.
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PMID:Reinnervation of dopamine neurons by regenerating serotonin axons in the rat medial zona incerta. A combined radioautographic and immunocytochemical ultrastructural study. 290 80

Pretreatment of guinea pigs with 6-hydroxydopamine in vivo for 24 h (250 mg/kg i.p.) reduced the norepinephrine and tyrosine hydroxylase contents of varicosities isolated from ileal myenteric plexus by 91 and 89%, respectively, indicating extensive destruction of noradrenergic varicosities. Destruction appeared to be restricted to noradrenergic varicosities because 5-hydroxytryptamine contents were unaffected. In vivo 6-hydroxydopamine treatment reduced the K+- and veratridine-evoked release of ATP from myenteric varicosities by 56 and 63%, respectively, indicating that much, but not all, of the evoked release of ATP probably originated from noradrenergic varicosities. Pretreatment of guinea pigs with 5 mg/kg of reserpine i.p. depleted norepinephrine contents of isolated varicosities by 90% but did not significantly reduce K+- or veratridine-evoked release of ATP, suggesting that the exocytotic release process was unaffected by reserpine. Selective destruction of serotonergic varicosities by treatment of guinea pigs with 50 mg/kg of desmethylimipramine i.p. followed by 40 mg/kg of 5,7-dihydroxytryptamine s.c. failed to diminish K+- or veratridine-evoked release of ATP from myenteric varicosities, indicating that the nonadrenergic release of ATP did not arise from serotonergic varicosities.
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PMID:Adrenergic and possible nonadrenergic sources of adenosine 5'-triphosphate release from nerve varicosities isolated from ileal myenteric plexus. 392 25

1. 5,6-dihydroxytryptamine (5,6-DHT) or a lesion of the raphe centralis superior (RCS) cause significant decreases in the serotonin (5-HT) content and significant increases in the tyrosine hydroxylase activity in the locus coeruleus (LC) of the rat. This suggests that noradrenaline (NA) synthesis is controlled by serotonin-containing neurons in the raphe system via their terminals in the LC. 2. Radioautography after intraventricular infusion of tritiated serotonin (3H-5-HT) and biochemical determinations of endogenous 5-HT content showed an almost complete disappearance of serotoninergic axonal varicosities and content in the LC region 10-15 days after intraventricular administration of 75 micrograms of 5,6-DHT. Two to 4 months after neurotoxin administration, 5-HT fibers had regrown in the LC but, contrary to the normal innervation pattern, the majority of them invaded the medial most portion of the nucleus and the adjacent subependymal region. The LC region regained almost all of its endogenous 5-HT content in the same time period. 3. Functional recuperation of these 5-HT fibers was demonstrated by the fact that the RCS had, after regeneration, the same functional control on NA synthesis as in the normal animal.
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PMID:Functional recuperation of the serotoninergic innervation in the rat locus coeruleus. 611 4

Myocardial noradrenaline (NA) content, together with the activities of the enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was measured in biopsy specimens taken during cardiac surgery from patients with various heart diseases. Fluorescence histochemical studies were also performed on comparable specimens. The mean NA content in patients with symptomatic ischaemic heart disease (IHD) was significantly higher than that in patients with valvular heart disease (VHD), atrial septal defect (ASD) or congestive heart failure (CHF). The lowest mean NA content was found in patients with CHF. The activities of TH and DBH were highest in the IHD group, although the differences between IHD and VHD groups were not significant. Histochemical investigations of adrenergic structures showed less fluorescence intensity in the CHF than in the other 3 groups. On the other hand, the density of the adrenergic nerve net and the size and number of varicosities were greatest in patients suffering from IHD. The significance of these results is discussed in relation to the pathophysiological mechanisms underlying these various disease conditions. In IHD the high myocardial NA content creates local conditions for excessive NA release into the myocardial interstitium at the onset of ischaemia, which is known to result in several adverse local consequences.
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PMID:Myocardial catecholamines and their biosynthetic enzymes in various human heart diseases. 612 8


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