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)

Embryonic striatal grafts develop a modular organization in which patches of tissue enriched in many transmitter substances characteristic of striatum (P regions) are embedded in surrounds (NP regions) expressing only low levels of these substances. Catecholaminergic fibers from the host brain, identified by their expression of tyrosine hydroxylase (TH), grow into such grafts and selectively terminate in the striatum-like P regions. This terminal pattern suggests that cell-cell affinities between neurons of the substantia nigra and striatum may play a role either in the aggregation of the striatal cells into P regions, or in the targeting of the TH-positive fibers to the cell clusters. In the present study, we tested the first of these possibilities. Striatal grafts derived from embryonic day 15 striatal primordia were implanted into the ibotenate-damaged host striatum of rats previously treated with 6-hydroxydopamine (6-OHDA) to destroy TH-containing dopaminergic nigrostriatal afferents. The 6-OHDA lesions that eliminated nearly all TH-like immunostaining in the host striatum also resulted in disappearance of nearly all TH-positive fibers in the grafts. In this dopamine-depleted environment, the grafts nevertheless developed a clear modular organization. They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers. These observations suggest that the ingrowth of TH-positive fibers from the host is not obligatory for the sorting out of striatal from nonstriatal cells during the formation of P regions in embryonic striatal grafts. Despite the fact that dopaminergic denervation of the host striatum did not disrupt either the aggregation of grafted cells into P regions or the acquisition of striatal neurochemical phenotypes by cells in the P regions, there were clear differences between the staining patterns of these grafts and grafts placed into dopamine-innervated striatum. Most striking was a sharp increase of met-enkephalin-like immunostaining in the P zones of the denervated grafts. Upregulation of met-enkephalin is known to occur in the dopamine-depleted mature striatum, and was observed in the parts of host striatum surrounding the grafts on the side ipsilateral to the 6-OHDA lesions. This result suggests that functional interactions between dopaminergic and enkephalinergic systems can occur in the striatal circuits reconstructed by embryonic striatal grafting. More generally, our results suggest that TH-containing afferents from the host striatum, though not required for induction and maintenance of striatal phenotypy in striatal grafts, can chronically regulate neurotransmitter/neuromodulator expression in neurons of the striatum-like P zones in a manner similar to that found for the normal striatum.
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PMID:Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia. 127 38

In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects of olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) - 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) - 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) - 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70-80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) - 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) - 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.
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PMID:Postnatal X-ray irradiation effects on glomerular layer of rat olfactory bulb: quantitative and immunocytochemical analysis. 135 42

Many dopaminergic cells of the substantia nigra are known to contain the calcium-binding proteins calretinin and calbindin-D28k. Catecholaminergic cell groups throughout the rat brain were therefore examined by two-colour immunofluorescence to determine whether they too contained these calcium-binding proteins as well as tyrosine hydroxylase (TH). Some TH+ cell groups are mostly positive for both calretinin and calbindin, notably in the ventral tegmental area, the interfascicular nucleus, and parts of the substantia nigra. Other TH+ cell groups in the midbrain, hindbrain and hypothalamus are very diverse; different cell groups are positive for calretinin, or calbindin, or both, or neither. In the olfactory bulb, entirely separate sets of periglomerular cells are positive for TH, calretinin and calbindin. However, there is considerable heterogeneity in calcium-binding protein expression within most cell groups, even in the substantia nigra. This could be a sign that calcium-binding proteins are regulated according to aspects of neuronal activity.
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PMID:Immunohistochemical markers in rat brain: colocalization of calretinin and calbindin-D28k with tyrosine hydroxylase. 135 63

It has been shown that morphologic and biochemical presynaptic markers of dopaminergic terminals are preserved in a unilateral experimental model of neonatal hypoxic-ischemic injury to the striatum. As the substantia nigra is spared direct injury in this model, we anticipated that the number of tyrosine hydroxylase-positive dopaminergic neurons projecting to the striatum would also be normal. We have found, however, that following unilateral neonatal striatal injury the number of ipsilateral tyrosine hydroxylase-positive neurons is decreased, as is the mean area of the substantia nigra pars compacta. The decrease in neurons is correlated with the decrease in striatal size (r = 0.7, P = 0.01). Neuron loss is most pronounced in the substantia nigra pars reticulata, where it is 50%. Calbindin-positive neurons in the dorsal tier of the substantia nigra pars compacta appear to be preserved. We also examined effects on the nigra following a neonatal excitotoxic striatal lesion made with quinolinic acid. We observed a decrease in the number of substantia nigra tyrosine hydroxylase-positive neurons in the absence of direct nigral injury, and the decrease was closely correlated with reductions in striatal area (r = 0.91, p < 0.01). While there are a number of possible explanations for these observations, one major possibility is that there has been a reduction in tyrosine hydroxylase-positive neurons due to a diminution in developmental target-derived trophic support from the striatum. If striatum-derived trophic support plays a role in the developmental regulation of substantia nigra neuron number, then abnormalities in this supportive relationship may play a role in the loss of these neurons in some animal models of developmental nigral degeneration, and some forms of human parkinsonism.
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PMID:Neonatal hypoxic-ischemic or excitotoxic striatal injury results in a decreased adult number of substantia nigra neurons. 135 61

The sources and histochemical characteristics of dopaminergic projections to motor and premotor areas of cortex were investigated in owl monkeys in which information from related studies was used to subdivide cortex into motor fields. Brainstem projections to frontal cortex were identified by injections of different fluorescent dyes in the primary motor cortex (M1) and the supplementary motor area (SMA), first identified by microstimulation. Injections were also placed in dorsal premotor cortex and lateral prefrontal cortex. The distribution of retrogradely labeled neurons was related to the location of tyrosine hydroxylase immunolabeled neurons on the same or alternate brain sections to identify the dopamine (DA) neurons. All DA cortically projecting neurons were located in the A8-A10 complex, largely in its dorsal components, including the parabrachial pigmented n. of the ventral tegmental area (VTA), pars gamma of the substantia nigra compacta, and the dorsal part of the retrorubral area (A8). Fewer cells were in the midline groups of VTA (n. linearis rostralis and caudalis) and in the n. paranigralis. DA neurons projecting to M1, SMA, and prefrontal cortex were largely intermixed, and some of these neurons were double or triple labeled by the fluorescent dyes, indicating collateralization to two or three fields; DA cells projecting to M1 were more numerous than to the other locations. The dorsal components of the A8-A10 complex from which arose the DA mesocortical projection were also characterized by the presence of calbindin-immunoreactive neurons and by a dense neurotensin and noradrenergic terminal innervation. Compared to rodents or felines, the DA neurons projecting to the lateral frontal lobe of primates appear to be shifted dorsally and laterally in the nigral complex. The topographic overlap, partial collateralization, and common histochemical characteristics of the DA mesocortical neurons projecting to different fields of the lateral frontal lobe suggest that some degree of functional unity exists within this projection.
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PMID:Topography and collateralization of the dopaminergic projections to motor and lateral prefrontal cortex in owl monkeys. 136 30

The anatomy of melanin-containing neurons and other midbrain structures was examined by tyrosine hydroxylase (TH), calbindin D28k, and substance P immunostaining. Greater than 95% of cells in the substantia nigra pars compacta contained melanin, but densely packed cells in a ventral tier had a low content of melanin and loosely packed cells in a dorsal tier had a high content of melanin. Approximately 60% in the gamma group and 40% in the retrorubral nucleus had a low content of melanin. TH immunostaining was moderate in both the ventral and dorsal tiers, but more intense in the gamma group and retrorubral nucleus. Calbindin D28k was absent from the ventral and dorsal tiers, but present in the gamma group and retrorubral nucleus. In the light of primate tracing studies these findings suggest that the ventral tier of the pars compacta projects to striosomes of the striatum and the dorsal tier, gamma group and retrorubral nucleus to the matrix compartment. The ventral tier is more vulnerable than the dorsal tier in Parkinson's disease, but the cells contain less melanin. Neither tier contains calbindin D28k. This differential vulnerability between the ventral and dorsal tiers cannot be explained by melanin or calbindin D28k.
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PMID:Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson's disease. 138 1

Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9 months of life; control monkeys were reared socially (SR) with mothers and peers. Subjects were killed at 19-24 yr of age. Because the behaviors of SD monkeys are reminiscent of changes in striatal or amygdalar function, we used immunocytochemistry for substance P (SP), leucine-enkephalin (LENK), somatostatin, calbindin, and tyrosine hydroxylase (TH) to evaluate qualitatively and quantitatively patterns of neurotransmitter marker immunoreactivity within subcortical regions. In SD monkeys, the chemoarchitecture of the striatum was altered. Neuronal cell bodies and processes immunoreactive for SP and LENK were depleted markedly in patch (striosome) and matrix regions of the caudate nucleus and putamen; the average density of SP-immunoreactive neurons was reduced 58% relative to SR monkeys. Calbindin and TH immunoreactivities were diminished in the matrix of caudate and putamen of SD monkeys. TH-immunoreactive neurons, but not cresyl violet-stained neurons, in the substantia nigra pars compacta were decreased (43%) in SD monkeys. Peptide-immunoreactive terminals were reduced in the globus pallidus and substantia nigra in SD monkeys. The nucleus accumbens was the least affected of striatal regions. Striatal somatostatin immunoreactivity wa qualitatively and quantitatively similar in SD and SR monkeys. Several regions, for example, bed nucleus of the stria terminalis, amygdala, and basal forebrain magnocellular complex, that were in the same sections and are enriched in these markers did not appear altered in SD monkeys, suggesting a regional specificity for vulnerability. The altered chemoarchitecture of some basal ganglia regions in adult monkeys that experienced social deprivation as infants suggests that the postnatal maturation of neurotransmitter phenotypes in some structures is influenced by social environment. Abnormal motor and psychosocial behaviors resulting from this form of social/sensory deprivation may result from alterations in peptidergic and dopaminergic systems within the basal ganglia.
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PMID:Social deprivation of infant rhesus monkeys alters the chemoarchitecture of the brain: I. Subcortical regions. 168 26

In cynomolgus monkeys, midbrain neurons immunoreactive (IR) for the calcium-binding protein calbindin D-28k (CaBP) occur principally in the dorsal tier of substantia nigra pars compacta (SNc) and in the ventral tegmental area (VTA), and most of these neurons co-express tyrosine hydroxylase (TH). In monkeys rendered parkinsonian (PD) after MPTP injections, CaBP-IR neurons are much less severely affected than TH-IR neurons in SNc and in VTA, and most spared neurons in SNc/VTA display both CaBP and TH immunoreactivity. These results reveal that, in contrast to the situation in other neurodegenerative diseases, CaBP may be used as a marker for a specific neuronal population that is less prone to degeneration in Parkinson's disease.
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PMID:Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. 168 19

Dopamine neurons have been demonstrated with the use of tyrosine hydroxylase (TH)-immunohistochemistry in the retina of Meriones shawi, a wild species of pigmented sand rat, in order to compare their morphology, density, and distribution with those in albino laboratory rat. The morphology and density of TH-immunoreactive cells were quite comparable in the two species: the dopamine cell population was composed of amacrine cells, displaced amacrine cells, and interplexiform cells, these latter being more numerous in the albino rat. The distribution of dopamine cells was more homogeneous in the sand rat retina where a peak density in the area centralis was not observed. The relationships between TH-immunoreactive cells and horizontal cells, demonstrated by their immunoreactivity to calbindin, have been observed in view of the dopamine action driven by scleral processes of interplexiform cells. A close vicinity occurred between 40% of the TH-immunoreactive cell and horizontal cell somata within the inner nuclear layer.
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PMID:Morphology, density and distribution of tyrosine hydroxylase immunoreactive cells in the retina in the gerbil Meriones shawi. Relationships with horizontal cells. 168 40

The arrangement of the enteric nerve plexuses in the colon of the guinea-pig and the distributions and projections of chemically specified neurons in this organ have been studied. Immunoreactivity for neuron specific enolase was used to examine the total population of neurons and individual subpopulations were studied using antibodies raised against calbindin, calcitonin gene-related peptide (CGRP), leu-enkephalin, gastrin releasing peptide (GRP), galanin, gamma aminobutyric acid, neurokinin A, neuropeptide Y (NPY), somatostatin, substance P, tyrosine hydroxylase and vasoactive intestinal peptide (VIP). Neuronal pathways within the colon were lesioned using myotomy and myectomy operations and extrinsic pathways running between the inferior mesenteric ganglia and the colon were also severed. Each of the antibodies revealed nerve cells and nerve fibres or only nerve fibres within the wall of the colon. VIP, galanin and GRP were in anally projecting pathways in the myenteric plexus, as they are in other species. In contrast, there are differences in the projection directions of enkephalin, substance P, NPY and somatostatin nerve fibres between regions and species. Surprisingly, somatostatin and NPY fibres have opposite projections in the small intestine and colon of the guinea-pig. The majority of nerve fibres that innervate the circular muscle, including fibres with immunoreactivity for VIP, enkephalin, substance P, NPY, galanin and GRP come from the myenteric ganglia. The mucosa is innervated by fibres from both the myenteric and submucous ganglia. The present results suggest that the guinea-pig distal colon is a suitable place in which to determine relations between structure, neurochemistry and functions of enteric neural circuits.
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PMID:Projections of chemically-specified neurons in the guinea-pig colon. 170 5


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