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

Detailed study of developmental changes in the enteric nervous system is necessary to disclose the pathogenesis of Hirschsprung's and allied disease, some of which have hypoplastic ganglia. Therefore experiments were undertaken to study the fate of neural crest cells that develop in the rat gut during ontogeny. A polyclonal antibody against ret proto-oncogene product (c-Ret protein) and various monoclonal antibodies against neural markers (tyrosine hydroxylase, dopamine beta hydroxylase, microtubule-associated protein 5, microtubule-associated protein 2 and 160-kd neurofilaments) were used to identify neural crest-derived cells in rat embryos (10.5 to 15.5 days' gestation) and adult rats using a double immunostaining method. C-Ret protein was an early marker of lineage determination in the development of the enteric nervous system (11.5-day embryo: E 11.5). C-Ret-positive cells transiently coexpressed tyrosine hydroxylase, which also was observed in the vagal crest-derived precursors of enteric neurons (days E 11.5 to E 13.5). These cells also coexpressed other neural markers in the proximal gut. Expression of neural markers migrated to the distal intestine during development. This study found a discrepancy between the time when these markers appeared in the cranial and when they appeared in the caudal intestine. Tyrosine hydroxylase-positive cells did not appear in the postumbilical gut. The formation of the primitive neural network in the entire myenteric plexus at day E 15.5 was demonstrated by c-Ret protein. Other neural markers were lost or bad decreased immunoreactivity throughout the entire intestine of the E 15.5 and adult animals. In conclusion, (1) c-Ret protein is one of the earliest markers of lineage determination in the development of the enteric nervous system, (2) each neural marker is expressed at its own time and differs in spatial developmental lineage, (3) c-Ret protein and other neural markers are transiently expressed by a particular group of neural cells during the embryonic period, (4) there is a subpopulation of cells that has never transiently expressed tyrosine hydroxylase in the postumbilical gut, which may have originated from tissue other than the vagal crest, and (5) the primitive neural network in the myenteric plexus was completed at day E 15.5.
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PMID:ret Proto-oncogene product is a useful marker of lineage determination in the development of the enteric nervous system in rats. 902 62

Mesencephalic dopaminergic neurones typically require the presence of serum for their survival in culture. However, the present study, outlines how neurones from the rat ventral mesencephalon (E14-16) were successfully cultured in serum-free, antioxidant-rich Neurobasal medium supplemented with B27 components. Moreover, immunostaining with mouse monoclonal microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) from day 1 to 7 in vitro revealed these cultures were primarily neuronal (80-95%). Additionally, immunostaining with tyrosine hydroxylase (TH) revealed these cultures contained a relatively constant population of TH-positive neurones (5%) which were presumed to be dopaminergic. These primary cultures offer considerable advantages for the study of mesencephalic, TH-positive, dopaminergic neurones under conditions where milieu can be readily manipulated in the virtual absence of glia and without the confounding influence of serum.
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PMID:Development and survival of rat embryonic mesencephalic dopaminergic neurones in serum-free, antioxidant-rich primary cultures. 932 28

Metabotropic glutamate receptors (mGluRs), which couple glutamate to second messengers, have important roles in the regulation of movement by the basal ganglia. We used two polyclonal antisera to mGluR1a and mGluR2/3 and confocal laser microscopy to investigate the localization of these receptors in the basal ganglia of the rat. The mGluRs were visualized in combination with an antibody to tyrosine hydroxylase (TH), an antibody to microtubule-associated protein 2 (MAP2, a dendritic marker), or SV2 (an antibody to a protein associated with presynaptic terminals). In the neostriatum, punctate mGluR1a immunoreactivity (ir) was present in the neuropil. This staining did not colocalize with MAP2-ir or SV2-ir and was not altered by decortication or unilateral 6-hydroxydopamine (6-OHDA) lesions. In the globus pallidus and substantia nigra pars reticulata, however, mGluR1a-ir was tightly clustered along large MAP2-ir dendrites. In contrast to the variations in mGluR1a-ir staining, similar punctate neuropil mGluR2/3-ir staining was observed within all basal ganglia structures. In the neostriatum, these puncta were abundant; unlike mGluR1a, many mGluR2/3-ir puncta colocalized with SV2-ir, and striatal mGluR2/3-ir puncta were markedly reduced in number after decortication. Neither mGluR1a-ir nor mGluR2/3-ir could be detected in TH-ir soma within substantia nigra pars compacta, or in TH-ir striatal terminals. Overall, our observations suggest that mGluR1a and mGluR2/3 receptors have distinct cellular localizations in different components of the basal ganglia circuitry and are likely to subserve distinct functions. Our data support the presence of mGluR2/3 on the terminals of corticostriatal afferents, where they may regulate glutamate release. In contrast, mGluR1a appears to be a postsynaptic receptor of neurons in the neostriatum, globus pallidus, and substantia nigra pars reticulata.
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PMID:Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia. 945 72

Enteric neurons have distinct neurochemical codings in each species. The basal tone of the gastrointestinal tract of the rabbit is low and produces neurally evoked pendular movements. Therefore, it might have an innervation pattern different from that of other laboratory animals. We have characterised myenteric neuron populations in rabbit ileum with neurochemical markers that are known to be associated with distinct cell types and/or fibre systems in the myenteric plexus. The density of nerve cells estimated with the NADH-diaphorase technique was about 2500 cells/cm2 and most, if not all, neurons contained microtubule-associated protein 2. NADPH-diaphorase-positive cells were numerous. One cell type was large and emitted long straight processes, whereas small cells bore thin filamentous dendrites. Neurons immunoreactive for 28-kDa calcium-binding protein were rare. Over 70% of them had very strongly labelled lamellar dendrites. Their axons were beaded and formed pericellular baskets around unstained somata. We found very few small tyrosine-hydroxylase-positive cells. The fibre network in the plexus was very strong; the axons formed many pericellular baskets. In double labelling studies, no co-localisation was revealed between the 28-kDa calcium-binding protein and NADPH-diaphorase. Some fibres containing 28-kDa calcium-binding protein formed only a few contacts on somata of NADPH-diaphorase-positive cells. None of the NADPH-diaphorase-labelled cells were found to be stained for tyrosine hydroxylase. Tyrosine-hydroxylase-positive fibres rarely made pericellular baskets on the surface of NADPH-diaphorase-positive somata. Strongly immunolabelled pericellular baskets were never observed around NADPH-diaphorase-positive cell somata. The results suggest that myenteric neurons in rabbit comprise distinct and characteristic neurochemical properties that are different from the rodent pattern. Therefore, the explanation of the motility pattern of rabbit intestine can be approached on a chemical neuroanatomical basis.
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PMID:Some neurohistochemical properties of nerve elements in myenteric plexus of rabbit ileum: similarities and dissimilarities to the rodent pattern. 956 Apr 71

In rat brain substantia nigra catecholamine neurons in vitro, a sensitive indicator of excitatory amino-acid-induced damage is dendritic degeneration that precedes the loss of the cell body. The present study has shown that dendritic loss is not specific for excitatory amino acids and is an early indicator of neurodegeneration produced by numerous agents that initiate damage by different primary cellular actions. Rats were anesthetised by fluothane inhalation and killed, and the brain was rapidly removed. Three-hundred-micrometer-thick slices containing substantia nigra were incubated for 2 h at 35 degrees C in the presence or absence of kainic acid (50 microM), 1-methyl-4-phenylpyridinium ion (10 or 50 microM), ouabain (10 or 30 microM), 6-hydroxydopamine (10 or 100 microM), potassium cyanide (100 microM or 1 mM), or elevated extracellular potassium chloride (25, 50, or 100 mM). The slices were fixed and recut into thin sections (30 micrometer) and substantia nigra dopamine neurons were immunolabeled for tyrosine hydroxylase coupled to diaminobenzidine. Both the cell body and the extensive dendritic projections were immunolabeled. Each agent caused a similar pattern of toxicity including loss of tyrosine-hydroxylase-immunolabeled dendrites at lower concentrations and damage to, or disintegration of, the cell bodies at higher concentrations. For example, 100 microM potassium cyanide reduced the proportion of substantia nigra neurons which exhibited dendrites from 66 +/- 4% (SEM) in controls to 54 +/- 7%, without obvious changes in cell bodies. After 1 mM potassium cyanide, only 13 +/- 2% of substantia nigra neurons retained dendrites and cell bodies were shrunken or disintegrated. Loss of dendrites was also evident in substantia nigra neurons stained with cresyl violet or immunolabeled for microtubule-associated protein 2. The findings suggest that disruption of the dendritic arbor is an early indicator of neurodegeneration, irrespective of how this is initiated. The approach that we have developed may therefore prove valuable in investigating the mechanisms of degeneration of catecholamine neurons.
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PMID:Dendrite loss is a characteristic early indicator of toxin-induced neurodegeneration in rat midbrain slices. 1068 96

Fibroblast growth factor-2 (FGF-2) was injected into mouse cerebral ventricles at embryonic day (E) 14 in utero and its effects on developing brain morphology and expression of various cell- or differentiation-associated protein markers in the cerebral cortex were examined. High doses of FGF-2 (200 or 300 ng) caused encephalic alternations such as deformation of the calvarium, enlargement of the ventricular spaces, and thinning of the cerebral cortex. There was no gross abnormality in the alignment of the cerebral neuronal layers, however, both cell number and cell density of the upper layers (II/III) and the lower layers (IV-VI) of the cerebral cortex were increased. Brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase, nestin, and microtubule-associated protein 2 were aberrantly or ectopically expressed in the deep areas of the cerebral cortex. A substantial number of these cells coexpressed these antigens. These observations demonstrate that a subpopulation of neurons in the cortical deep layer abnormally differentiated or partly sustained their immature state following a single administration of FGF-2 at E14. Developmental analysis of localization of BDNF-positive cells suggested that the abnormality started around P5. Furthermore, cell migration was not affected by FGF-2 administration. FGF-2 seems to play predominant roles in the proliferation of neuronal precursors and in neuronal differentiation in the developing mouse cerebral cortex even at relatively late stages of brain neurogenesis.
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PMID:Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex. 1149 57

Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) are potential therapeutic molecules for the treatment of Parkinson's disease (PO). Here we compare the effects of BMP3, 5, 6, and 7 and GDF5 and 6 in a rat mesencephalic cell culture system that reflects the developmental stage of neurons around birth. High concentrations of BMP5, 6, and 7 and GDF5 and 6 induced astroglial cell fate and a depletion of oligodendrocytes. Only BMP5, 6, and 7, however, significantly increased the number of tyrosine hydroxylase (TH)-positive neurons and induced nuclear translocation of the phosphorylated BMP-restricted Smad in a substantial number of TH- and microtubule-associated protein 2(MAP2ab)-positive cells. None of the proteins protected TH-positive cells against 6-hydroxydopamine-induced oxidative stress. BMP3 was without any effect throughout the studies. We conclude that BMP5, 6, and 7 act directly and independently on precursors of the dopaminergic and astroglial lineage and induce their differentiation. In contrast, GDF5 and 6 primarily affect nonneuronal cells in mesencephalic cultures of this stage.
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PMID:Bone morphogenetic proteins but not growth differentiation factors induce dopaminergic differentiation in mesencephalic precursors. 1249 80

We established adrenal medullary cell lines from transgenic mice expressing an oncogene, the temperature-sensitive simian virus 40 large T-antigen, under the control of the tyrosine hydroxylase promoter. A clonal cell line, named tsAM5D, conditionally grew at a permissive temperature of 33 degrees C and exhibited the dopaminergic chromaffin cell phenotype as exemplified by the expression pattern of mRNA for catecholamine-synthesizing enzymes and secretory vesicle-associated proteins. tsAM5D cells proliferated at the permissive temperature in response to basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). At a non-permissive temperature of 39 degrees C, bFGF and CNTF acted synergistically to differentiate tsAM5D cells into neuron-like cells. In addition, tsAM5D cells caused to differentiate by bFGF plus CNTF at 39 degrees C became dependent solely on nerve growth factor for their survival and showed markedly enhanced neurite outgrowth. In the presence of bFGF and CNTF, the morphological change induced by the temperature shift was associated with up-regulated expression of neuronal marker genes including neuron-specific enolase, growth-associated protein-43, microtubule-associated protein 2, neurofilament, and p75 neurotrophin receptor, indicating that the cells underwent neuronal differentiation. Thus, we demonstrated that tsAM5D cells could proliferate at permissive 33 degrees C, and also had the capacity to terminally differentiate into neuron-like cells in response to bFGF and CNTF when the oncogene was inactivated by shifting the temperature to non-permissive 39 degrees C. These results suggest that tsAM5D cells should be a good tool to allow a detailed study of mechanisms regulating neuronal differentiation.
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PMID:Temperature-dependent, neurotrophic factor-elicited, neuronal differentiation in adrenal chromaffin cell line immortalized with temperature-sensitive SV40 T-antigen. 1275 72

Glucoprivation induced by 2-deoxy-D-glucose (2DG) suppresses pulsatile luteinizing hormone (LH) secretion in female rats. The suppression is enhanced in the presence of estrogen. In the present study, 2DG-induced Fos expression was examined in the solitary tract nucleus (NTS), hypothalamic paraventricular nucleus (PVN), raphe obscurus nucleus (ROb) and raphe pallidus nucleus (RPa), which have been previously suggested to be involved in glucoprivation-induced suppression of LH secretion in female rats. Ovariectomized (OVX) or estrogen-primed ovariectomized (OVX+E(2)) rats were injected intravenously with 2DG (400 mg/kg BW). The brain was removed 1 h after the injection. The number of Fos-like-immunoreactive (Fos-li) cells in the PVN and NTS was significantly increased in OVX+E(2) rats compared with control groups, but did not show a significant increase in the OVX group. Few Fos-li cells were observed in the ROb and RPa in all groups. All of the Fos-li cells in the PVN and NTS were neurons because they had immunoreactivities to microtubule-associated protein 2. Some Fos-li cells (8.3%) had tyrosine hydroxylase-like immunoreactivities in the NTS in 2DG-treated OVX+E(2) rats. These results suggest that neurons in the PVN and NTS are involved in the estrogen-dependent neural cascade mediating glucoprivic suppression of LH secretion in female rats.
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PMID:Glucoprivation-induced Fos expression in the hypothalamus and medulla oblongata in female rats. 1496 40

We previously established a primary culture system of the accessory olfactory bulb (AOB) to investigate the functional roles of individual types of neuron in pheromonal signal processing. However, the detailed characteristics of cultured AOB neurons were not yet apparent. In the present study, we address the cytological aspects of cultured AOB neurons using immunocytochemical staining methods. Cultured AOB neurons were compared with cultured main olfactory bulb (MOB) neurons in neuronal composition, maturational time course, and cell size. The number of total neurons, measured by microtubule-associated protein 2 (MAP2) immunostaining, progressively decreased, and glutamic acid decarboxylase positive (GAD+) interneurons were scarcely changed in their number in both AOB and MOB cultures over the culture periods. In contrast, the number of tyrosine hydroxylase positive (TH+) neurons in AOB cultures showed a slight, but significant, increase over time in culture, while those in MOB cultures remarkably decreased. The numbers of total neurons and GAD+ neurons were significantly greater in AOB cultures than in MOB cultures at all investigated time points. However, the numbers of TH+ neurons were lower at 7 days in vitro (DIV) and greater at 21 DIV in AOB cultures than in MOB cultures. The somatic sizes of all types of neurons at 14 DIV were significantly larger in AOB cultures than in MOB cultures. Furthermore, the frequency distributions of somatic sizes of total, GAD+, and TH+ neurons were significantly different between AOB and MOB cultures. These subtle differences in vitro may reflect in vivo differences between the AOB and MOB.
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PMID:Differences in development and cellular composition between neuronal cultures of rat accessory and main olfactory bulbs. 1559 91


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