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)

Although the entorhinal cortex is a key structure connecting the hippocampal formation with the rest of the cerebral cortex, little is known about its early chemoanatomical development in primates. In the present study, a cytoarchitectonic analysis and immunocytochemical detection of somatostatin, neurotensin, parvalbumin, calbindin-D 28K, DARPP-32, as well as tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin, were carried out on serial sections of the entorhinal cortex of six rhesus monkey fetuses aged E47 to E90 (gestation period 165 days). At E56 the cortical plate of the entorhinal cortex already exhibited a sublamination; at E64 the lamina dissecans was partly formed, allowing the emergence of the lamina principalis externa and interna, and at E83 most of the regional and laminar subdivisions characteristic of the adult cortex could be identified, except for the rhinal sulcus restricted to a small dimple. The neurochemical development paralleled the early cytoarchitectonic differentiation, both largely preceding that of the neighboring cortical areas. The somatostatin-like immunoreactive innervation, first detected at E56, was very dense as early as E64 and displayed by E83 a laminar distribution similar to that found in the adult. Labeled neurons indicated an intrinsic origin for this innervation but an extrinsic connection might be present as labeled fibers in the subplate of the entorhinal cortex were in continuity with positive fibers in the intermediate zone of the hippocampal formation. A faint neurotensin-like immunoreactivity first detected at E64 became prominent at E83 in the entorhinal cortex but stopped abruptly at the anlage of the rhinal sulcus. The lack of neurotensin-labeled neurons contrasted with their presence in other parts of the hippocampal region and suggested a precocious extrinsic connection. Only rare parvalbumin-LIR neurons were detected at midgestation, whereas calbindin-D 28K was expressed from E47 on in Cajal-Retzius cells and from E56 on in various types of neurons in the cortical plate and subplate. Most characteristic was a category of medium-sized, deeply stained calbindin-LIR neurons, present only in the lamina principalis externa and possibly corresponding to the population of large neurons described by Kostovic et al. (1990, Soc Neurosci Abstr 16:846) in early developing entorhinal cortex of human fetuses. These and probably other neurons were also DARPP-32-positive, suggesting the possibility of an early dopaminergic regulation. Indeed, the monoaminergic innervation of the entorhinal cortex was detected from E56 on and gradually increased in density, displaying areal and laminar differences in the distribution of the dopaminergic, noradrenergic, and serotoninergic afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurochemical development of the hippocampal region in the fetal rhesus monkey. I. Early appearance of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex during the first half of gestation (E47 to E90). 835 10

Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
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PMID:Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. 835 18

A number of marker substances for neuronal and neuroendocrine cells have been demonstrated in the cytoplasm of the interstitial Leydig cells of human testes using basic immunocytochemical methods and some of their modifications. We were able to reveal immunoreactivity for enzymes involved in the synthesis of the catecholamines dopamine and noradrenaline (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase), for the indolamine 5-hydroxytryptamine (serotonin), as well as for a number of well-known neuronal markers such as the neurofilament protein 200, synaptophysin, chromogranin A + B, the neural cell-adhesion molecule (N-CAM), the microtubule-associated protein (MAP-2), and the calcium-binding proteins: S-100, calbindin and parvalbumin. Immunoreactivity for these substances was found in the majority of the interstitial cells although differences in the staining intensity among the individual Leydig cells and among Leydig cells from different patients were observed. At the electron-microscopic level the Leydig cell cytoplasm was seen to contain microtubules, intermediate- and microfilaments as well as clear (40-60 nm) and dense-core (100-300 nm) vesicles, providing a morphological correlate for some of the immunocytochemical results. Although individual marker substances are not absolutely specific for nerve and neuroendocrine cells, the results obtained, together with the already established neuron-specific enolase-, substance P-, methionine-enkephalin- and proopiomelanocortin (POMC)-derived peptide-like immunoreactivity, provide strong evidence for the neuroendocrine (paraneuronal, APUD-like) nature of the Leydig cells of the human testis.
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PMID:The Leydig cell of the human testis--a new member of the diffuse neuroendocrine system. 847 1

The neuroendocrine nature of a subset of Leydig cells has already been established. The present investigation deals with neuroendocrine characteristics of Leydig tumour cells. A number of neuroendocrine and neuronal markers were demonstrated in Leydig cell tumours of 7 men aged 25-41 years. The following substances were immunocytochemically tested in Leydig tumour cells: the monoamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, the indoleamine serotonin, the calcium-binding protein parvalbumin, the microtubule associated protein-2, neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and neuronal nitric oxide synthase (NOS). Compared to the normal interstitial cells beyond the tumours, all neoplastic cells showed a significantly weaker immunoreactivity for nerve cell markers as well as for testosterone and cyclic guanosine monophosphate (cGMP), which is usually accumulated by nitric oxide (NO). This provides evidence for a certain dedifferentiation of Leydig tumour cells. However, these results suggest that tumourous development of Leydig cells does not include loss of neuronal phenotype. Moreover, on the assumption that 'neuronal' Leydig cells exist beside 'non-neuronal' ones in normal testicular tissue, we propose the hypothesis that 'neuronal' Leydig cells can transform to tumour cells.
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PMID:Neuroendocrine characteristics of human Leydig cell tumours. 859 7

The present study compares the distribution of three calcium binding proteins, calbindin-D28k, calretinin, and parvalbumin, in the midbrain tegmentum of rats and humans. In order to compare the distributions of these proteins directly, the cytoarchitecture of this region was evaluated by using immunohistochemistry for tyrosine hydroxylase and substance P in serial sections in both transverse and horizontal planes. There was a high degree of homology in the cytoarchitecture of the three main dopaminergic regions identified. The A8 group was localised in the retrorubral fields, which extended rostrally into the midbrain reticular fields in the human. The A9 group corresponded to the substantia nigra, which was delimited by its dense substance P innervation. The heterogeneous A10 group, situated along the dorsal border as well as medial to the A9 group, comprised multiple nuclei. The distribution of calcium binding proteins was similar in both species, although a larger proportion of neurons contained these proteins in the rat. Calbindin-D28k was localised in neurons within A8 and A10 nuclei and within the caudomedial A9 region (and rostrolateral A9 in the rat only). Calretinin was localised in similar regions. In contrast, neurons containing parvalbumin were concentrated in the substantia nigra pars reticulata. The results suggest that few dopaminergic neurons receiving striatal input in the substantia nigra contain calcium binding proteins; rather, the nondopaminergic nigral neurons contain parvalbumin. Interestingly, dopaminergic neurons are more numerous in humans, whereas nondopaminergic neurons predominate in rats, which suggests that functional differences may exist between rats and humans.
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PMID:Cytoarchitectural distribution of calcium binding proteins in midbrain dopaminergic regions of rats and humans. 878 81

The neostriatum is one of the areas with relatively high levels of glial cell line-derived neurotrophic factor (GDNF) messenger RNA expression in the developing and adult brain. GDNF expression in the neostriatum has been suggested to be involved in promoting the survival of nigral dopaminergic neurons, acting as a target-derived neurotrophic factor. However, GDNF messenger RNA expression in the striatum starts several days before dopaminergic and other afferent neurons reach the striatum, suggesting additional trophic effects of this factor on striatal neurons. In the present report, we have examined whether GDNF is able to prevent the degeneration of striatal calbindin- and parvalbumin-immunoreactive neurons in a lesion model of Huntington's disease. Fischer 344 rat 3T3 fibroblast cell line expressing high levels of GDNF (F3A-GDNF) was used to assess the protective effect of this factor, on striatal neurons, against excitotoxicity. Quinolinate (34 nmol) was injected at two different coordinates, and calbindin, parvalbumin and tyrosine hydroxylase immunoreactivity were examined seven days after lesion. Dopaminergic afferents were spared after quinolinate injection, but the number of calbindin- and parvalbumin-immunoreactive neurons was decreased. Interestingly, implantation of F3A-GDNF cells increased the density of tyrosine hydroxylase staining in the intact and also in the quinolinate-lesioned striatum. Furthermore, GDNF partially protected calbindin- but not parvalbumin-immunoreactive neurons from quinolinate excitotoxicity. Instead, mock-transfected fibroblasts did not affect any of these parameters. Our results show that GDNF specifically protects a subpopulation of striatal calbindin-immunoreactive neurons against quinolinate lesion, suggesting that GDNF administration may have a potential therapeutic application in the prevention and treatment of striatonigral degenerative disorders.
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PMID:Glial cell line-derived neurotrophic factor protects striatal calbindin-immunoreactive neurons from excitotoxic damage. 893 Oct 1

We have localized the dopamine D1 receptor in rat retina using a subtype-specific monoclonal antibody. Immunolabelling can be detected in the inner and outer plexiform layers and in a number of cells in the inner nuclear layer. In the inner plexiform layer, labelled processes form four distinct horizontal bands and a series of patches. In order further to characterize the labelling pattern of the D1 receptor antibody, double-labelling experiments were performed with antibodies against population-specific neuronal markers in the retina. Antibodies against tyrosine hydroxylase, choline acetyltransferase, calretinin, calbindin, the glutamate transporter GLT-1, protein kinase C, recoverin and parvalbumin were co-applied with the D1 receptor antibody. With these cell markers we demonstrate that horizontal cells, at least three types of cone bipolar cells and a small number of amacrine cells are immunolabelled for the D1 receptor. In the inner plexiform layer, processes labelled by the D1 receptor antibody are co-stratified with processes labelled by the GLT-1 antibody. D1 receptor-labelled processes are not co-localized with the processes of amacrine cells and ganglion cells labelled by antibodies against tyrosine hydroxylase, choline acetyltransferase or calretinin. Our results indicate that dopamine D1 receptors are localized predominantly to horizontal cells and cone bipolar cells. Furthermore, the spatial disparity between dopaminergic processes and the site of the majority of D1 receptors supports the idea that in the retina dopamine acts as a neuromodulator that diffuses through extracellular space. The localization of D1 receptors to a number of identified cell types enables future physiological work to be directed towards specific synaptic circuits within the retina.
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PMID:Immunohistochemical localization of dopamine D1 receptors in rat retina. 895 93

Olfactory bulbs (OBs) from embryonic day 15 and 17 and postnatal day 1 mice were transplanted into the lateral ventricle of juvenile host mice without bulbectomy, and fine structural and chemical features of neurons and glia in the OB transplants were investigated immunocytochemically and electron microscopically. In the OB transplants there were neither clearly defined glomeruli nor layers, nor olfactory marker protein immunoreactive elements. However, chemically defined neuronal populations resembling those in the normal OBs such as those immunoreactive for gamma-aminobutyric acid (GABA), tyrosine hydroxylase and Ca(2+)-binding proteins (calbindin-D28K, calretinin, parvalbumin) were observed. Electron microscopically, dendrodendritic and somatodendritic reciprocal synapses, that is, synapses characteristic of the OB, were occasionally observed in the OB transplants. These results indicated that at least some embryonic or newborn mouse OB neurons and/or precursor cells could exhibit chemical properties and form typical synaptic contacts observed in normal OB, even when they received no inputs from olfactory receptor cells.
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PMID:Differentiation of chemically defined neuronal populations in the transplanted olfactory bulb without olfactory receptor innervation. 917 76

The striatum of the human brain has a highly differentiated neurochemical architecture visible in stains for many of the neurotransmitter-related molecules present in the striatum. The distributions for these chemical markers have never been analyzed comprehensively. We compared the distributions of multiple neurochemical markers in a serial-section analysis of the caudate nucleus, the putamen, and the ventral striatum in normal human brains. The cholinergic system was identified with choline acetyltransferase (ChAT). The organization of the cholinergic fiber system was compared with that of striatal systems expressing immunoreactivity for calbindin D28k, met-enkephalin, substance P, tyrosine hydroxylase, and parvalbumin. Each striatal region analyzed displayed a unique neurochemical organization. In the dorsal caudate nucleus, the distribution of all markers followed the classical striosome/matrix organization as previously reported. In the dorsal putamen, ChAT-staining was less intense, and striosomes were delineated primarily by unstained fiber bundles. In the ventral caudate nucleus/nucleus accumbens region, the boundaries of ChAT-stained regions were not always visible with stains for calbindin, enkephalin, and substance P. The ventral putamen displayed a similar organization, except in its lateral part, where ChAT-poor regions were often found adjacent to, rather than in register with, regions expressing low levels of the other markers (calbindin, enkephalin, substance P, and tyrosine hydroxylase). Our findings suggest that, in addition to the classical striosome-matrix organization visible in the dorsal caudate nucleus and putamen, there is further neurochemical differentiation in a large ventral part of the caudate nucleus and putamen and in the ventral striatum-nucleus accumbens proper. The more complex relationships among the different neurochemical systems in the ventral striatum may reflect the increase in size in the primate of striatal regions associated with association and limbic cortex.
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PMID:Neurochemical architecture of the human striatum. 921 37

Intrinsic, striatal tyrosine hydroxylase-immunoreactive (TH-i) cells have received little consideration. In this study we have characterized these neurons and their regulatory response to nigrostriatal dopaminergic deafferentation. TH-i cells were observed in the striatum of both control and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated monkeys; TH-i cell counts, however, were 3.5-fold higher in the striatum of MPTP-lesioned monkeys. To establish the dopaminergic nature of the TH-i cells, sections were double-labeled with antibodies to dopamine transporter (DAT). Immunofluorescence studies demonstrated that nearly all TH-i cells were double-labeled with DAT, suggesting that they contain the machinery to be functional dopaminergic neurons. Two types of TH-i cells were identified in the striatum: small, aspiny, bipolar cells with varicose dendrites and larger spiny, multipolar cells. The aspiny cells, which were more prevalent, corresponded morphologically to the GABAergic interneurons of the striatum. Double-label immunofluorescence studies using antibodies to TH and glutamate decarboxylase (GAD67), the synthetic enzyme for GABA, showed that 99% of the TH-i cells were GAD67-positive. Very few (<1%) of the TH-i cells, however, were immunoreactive for the calcium-binding proteins calbindin and parvalbumin. In summary, these results demonstrate that the dopaminergic cell population of the striatum responds to dopamine denervation by increasing in number, apparently to compensate for loss of extrinsic dopaminergic innervation. Moreover, this population of cells corresponds largely with the intrinsic GABAergic cells of the striatum. This study also suggests that the adult primate striatum does retain some intrinsic capacity to compensate for dopaminergic cell loss.
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PMID:Dopaminergic neurons intrinsic to the primate striatum. 925 87


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