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)

We investigated whether there is neurogenesis in the striatum of aged monkeys, and whether dopamine (DA) depletion induces the genesis of new DA neurons in this structure. Six aged macaques received repeated intraperitoneal injections of bromodeoxyuridine (BrdU) over a 3 week period to label dividing cells. Three macaques were injected in parallel with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to decrease dopaminergic innervation of the striatum. The brains were analysed 3 weeks after the last BrdU injection. In MPTP-treated aged macaques, the number of tyrosine hydroxylase (TH) immunoreactive (ir) striatal neurons increased 2.3-fold compared with controls. These TH-ir striatal cells did not express dopamine beta hydroxylase (DBH) but the dopamine transporter (DAT), suggesting that they are functional DA neurons. They were also negative for calbindin (CB), neuropeptide Y (NPY) and parvalbumin (PV), and a small proportion expressed calretinin (CR). This suggests that these cells stained for TH are interneurons. All these cells also co-expressed glutamic acid decarboxylase (GAD). They thus resemble the small, aspiny, GABAergic interneurons. None of the BrdU-labelled cells in the striatum expressed the neuronal markers neuronal nuclei (NeuN), or GAD or TH, and none of TH-ir cells incorporated BrdU. These data indicate that neurogenesis did not occur in the striatum of aged macaques. The new striatal TH-ir neurons observed after DA depletion was therefore derived from pre-existing GABAergic interneurons. Understanding of the molecular signals mediating this phenotypic shift might help in developing novel and elegant strategies for a cell-based therapy for Parkinson's disease that would avoid many of the drawbacks of cell transplantation.
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PMID:New striatal dopamine neurons in MPTP-treated macaques result from a phenotypic shift and not neurogenesis. 1648 74

The cyto- and chemoarchitecture of the anterior olfactory nucleus and piriform cortex of the short-beaked echidna and platypus were studied to determine: (1) if these areas contain chemically distinct subdivisions, and (2) if the chemoarchitecture of those cortical olfactory regions differs from therians. Nissl and myelin staining were applied in conjunction with enzyme reactivity for NADPH diaphorase and acetylcholinesterase, and immunoreactivity for calcium-binding proteins (parvalbumin, calbindin and calretinin) and tyrosine hydroxylase. Golgi impregnations were also available for the echidna. In the echidna, the anterior olfactory nucleus is negligible in extent and merges at very rostral levels with a four-layered piriform cortex. Several rostrocaudally running subregions of the echidna piriform lobe could be identified on the basis of Nissl staining and calcium-binding protein immunoreactivity. Laminar-specific differences in calcium-binding protein immunoreactivity and NADPH-d-reactive neuron distribution were also noted. Neuron types identified in echidna piriform cortex included pyramidal neurons predominating in layers II and III and non-pyramidal neurons (e.g., multipolar profusely spiny and neurogliaform cells) in deeper layers. Horizontal cells were identified in both superficial and deep layers. By contrast, the platypus had a distinct anterior olfactory nucleus and a three-layered piriform cortex with no evidence of chemically distinct subregions within the piriform cortex. Volume of the paleocortex of the echidna was comparable to prosimians of similar body weight and, in absolute volume, exceeded that for eutherian insectivores such as T. ecaudatus and E. europaeus. The piriform cortex of the echidna shows evidence of regional differentiation, which in turn suggests highly specialized olfactory function.
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PMID:The anterior olfactory nucleus and piriform cortex of the echidna and platypus. 1649 95

Lifelong neurogenesis in vertebrates relies on stem cells producing proliferation zones that contain neuronal precursors with distinct fates. Proliferation zones in the adult zebrafish brain are located in distinct regions along its entire anterior-posterior axis. We show a previously unappreciated degree of conservation of brain proliferation patterns among teleosts, suggestive of a teleost ground plan. Pulse chase labeling of proliferating populations reveals a centrifugal movement of cells away from their places of birth into the surrounding mantle zone. We observe tangential migration of cells born in the ventral telencephalon, but only a minor rostral migratory stream to the olfactory bulb. In contrast, the lateral telencephalic area, a domain considered homologous to the mammalian dentate gyrus, shows production of interneurons and migration as in mammals. After a 46-day chase, newborn highly mobile cells have moved into nuclear areas surrounding the proliferation zones. They often show HuC/D immunoreactivity but importantly also more specific neuronal identities as indicated by immunoreactivity for tyrosine hydroxylase, serotonin and parvalbumin. Application of a second proliferation marker allows us to recognize label-retaining, actively cycling cells that remain in the proliferation zones. The latter population meets two key criteria of neural stem cells: label retention and self renewal.
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PMID:Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate. 1668 18

The substantia nigra pars reticulata (SNR) is involved in movement and seizure control. In male but not female postnatal day 15 (PN15) rats, GABAA receptor agonists depolarize the SNR neurons and increase the expression of the calcium-regulated gene KCC2 (potassium/chloride cotransporter). Moreover, in PN15 rat SNR, 7beta-estradiol down-regulates KCC2 expression only in the presence of depolarizing GABAA receptor responses. The hypothesis tested here was that GABAA receptors and estradiol also regulate the expression of the phosphorylated form of the transcription factor cAMP responsive element binding protein (phosphoCREB), in PN15 rat SNR and substantia nigra pars compacta (SNC). Rats were injected with muscimol or 17beta-estradiol or their vehicles, and killed 1 h later. Sections were stained with an antibody specific for phosphoCREB alone or counterstained with either tyrosine hydroxylase (TH)- or parvalbumin (PRV)-specific antibodies. Muscimol increased phosphoCREB-ir in male but not in female SN neurons. Using gramicidin perforated patch clamp of PN14-15 SNC neuron, it was shown that muscimol bath application depolarized male SNC neurons but did not significantly alter membrane potential in females. In males, 17beta-estradiol decreased phosphoCREB expression in all studied cell types. In females, 17beta-estradiol did not influence phosphoCREB expression in PRV-ir SNR cells, but increased it in the dopaminergic SN neurons. These data suggest that GABAA receptor activation and estradiol promote the sexual differentiation of the SN in a cell-type-specific manner, by influencing calcium-regulated gene transcription, and therefore promoting the acquisition of sex-specific roles of the SN in movement and seizure control.
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PMID:Sex- and cell-type-specific patterns of GABAA receptor and estradiol-mediated signaling in the immature rat substantia nigra. 1670 49

In an effort to understand better the neurochemical changes that occur in Parkinson disease, we have examined the expression patterns of the calcium-binding protein parvalbumin in the zona incerta in parkinsonian rats. Sprague-Dawley rats had small volumes of either saline (control) or 6 hydroxydopamine (6OHDA) injected into the medial forebrain bundle, the major tract carrying dopaminergic nigrostriatal axons. After various post-lesion survival periods, ranging from 2 hrs to 84 days, rats were perfused with formaldehyde and their brains processed for routine tyrosine hydroxylase (TH) or parvalbumin immunocytochemistry. In the 3 to 84 days post-lesion cases, there was an overall 50% reduction in the number of parvalbumin(+) cells in the zona incerta on the 6OHDA-lesioned side when compared to control. In the 2 hrs post-lesion cases, there was no substantial loss of parvalbumin(+) cells in the zona incerta after 6OHDA lesion, although in these cases (unlike the longer survival periods), there was limited loss of TH(+) cells in the midbrain on the lesion side. The loss of parvalbumin(+) cells from the zona incerta was due to a loss of antigen expression rather than a loss of the cells themselves, since the number of Nissl-stained cells in the zona incerta was similar on the control and 6OHDA-lesioned sides. In summary, our results indicate that a loss of the midbrain dopaminergic cells induces a major change in parvalbumin expression within the zona incerta. This change may have key functional and clinical implications.
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PMID:Reduction in parvalbumin expression in the zona incerta after 6OHDA lesion in rats. 1690 63

We investigated the structural and molecular organization of the extracellular matrix in Thylamys elegans, a marsupial representative of the mammalian order Didelphimorphia. Perineuronal nets (PNs) associated with distinct types of neurons were visualized by detection of chondroitin sulfate proteoglycans and hyaluronan, and by labeling with Wisteria floribunda agglutinin (WFA), a marker for PNs in the mammalian brain. In the neocortex of Thylamys, these methods revealed PNs on pyramidal cells. In contrast, parvalbumin-immunoreactive interneurons in the neocortex and hippocampal formation (displaying robust, WFA-labeled PNs in placental mammals) were ensheathed only with a delicate rim of hyaluronan and proteoglycans not detectable with WFA. The absence of WFA staining was characteristic also of some subcortical regions which contained PNs intensely labeled for chondroitin sulfate proteoglycan and hyaluronan. However, corresponding to placental mammals, numerous subcortical nuclei showed clearly WFA-stained PNs. Similar as in placental mammals, cholinergic basal forebrain neurons and tyrosine hydroxylase-immunoreactive neurons of the substantia nigra and locus coeruleus were devoid of PNs. Together with our earlier study on Monodelphis, the present results reveal that South American opossums show either a particular "marsupial" or "Didelphid" type of extracellular matrix chemoarchitecture, supporting the view that these components may vary phylogenetically as integral parts of neuronal physiology at the systems and single cell level.
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PMID:Organization of brain extracellular matrix in the Chilean fat-tailed mouse opossum Thylamys elegans (Waterhouse, 1839). 1699 16

Human fetal brain is a potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative diseases. We explored whether NSCs isolated from cortex and striatum of human fetuses, aged 6-9 weeks post-conception, maintain their regional identity and differentiate into specific neuron types in culture and after intrastriatal transplantation in neonatal rats. We observed no differences between cortex- and striatum-derived NSCs expanded as neurospheres in proliferative capacity, growth rate, secondary sphere formation, and expression of neural markers. After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2- and parvalbumin-containing neurons. However, whereas cortical NSCs produced higher number of glutamatergic and tyrosine hydroxylase- and calretinin-positive neurons, several-fold more neurons expressing the striatal projection neuron marker, DARPP-32, were observed in cultures of striatal NSCs. Human cortical and striatal NSCs survived and migrated equally well after transplantation. The two NSC types also generated similar numbers of mature NeuN-positive neurons, which were several-fold higher at 4 months as compared to at 1 month after grafting. At 4 months, the grafts contained cells with morphologic characteristics of neurons, astrocytes, and oligodendrocytes. Many of neurons were expressing parvalbumin. Our data show that NSCs derived from human fetal cortex and striatum exhibit region-specific differentiation in vitro, and survive, migrate, and form mature neurons to the same extent after intrastriatal transplantation in newborn rats.
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PMID:Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats. 1704 30

Bisphenol A (BPA), known as an environmental endocrine disrupter, is widely used in industry and dentistry. We investigated the effects of fetal and neonatal exposure to bisphenol A (BPA) on the brain development of mice. The density of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in substantia nigra was significantly decreased in BPA-exposed female mice (3 microg/g powder food), but not in the male mice, as compared with that of the control mice. The densities of calbindin D-28 K-, calretinin- and parvalbumin-IR neurons in the cerebral cortex were not different between BPA-exposed and the control mice. The present study indicates that chronic exposure of BPA during prenatal and neonatal periods causes a decrease of TH-positive neurons in substantia nigra only in female mice brain.
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PMID:Effects of pre- and neonatal exposure to bisphenol A on murine brain development. 1711 58

The ventral tegmental area (VTA), the origin of dopaminergic cell bodies that comprise the mesocorticolimibic DA system, is widely implicated in drug and natural reward, cognition, and several psychiatric disorders. In addition to dopaminergic neurons, this region is populated by GABAergic neurons, which both regulate the firing of their dopaminergic counterparts and send projections throughout the brain. Although the dopaminergic neurons of the VTA have been extensively characterized neuroanatomically, much less is known about the GABAergic neurons in this region. Recent data suggest that the rostro-caudal topographic organization of these GABAergic neurons may correspond to their ability to regulate drug reward. In the present study, we used immunohistochemical techniques to examine the frequency and topography of GABAergic neurons throughout the rostro-caudal axis of the VTA and the extent to which they coexpress other proteins, including tyrosine hydroxylase (a marker of DA neurons), cholecystokinin, parvalbumin, calretinin, and calbindin d 28k.
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PMID:Topographical organization of GABAergic neurons within the ventral tegmental area of the rat. 1711 19

Somatostatin (SRIF), as a neuroactive peptide in the CNS, exerts its actions via five subtypes of specific receptors (ssts). In this work, the localization of sst(5) was studied immunocytochemically in rat retinal amacrine cells (ACs). Labeling for sst(5) was diffusely distributed throughout the full thickness of the inner plexiform layer (IPL) and formed two distinct fluorescence bands in the distal part of the IPL. Double labeling experiments showed that sst(5) was expressed in GABAergic ACs. It was further shown that labeling for sst(5) was observed in both dopaminergic and cholinergic ACs, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), respectively. The immunostaining appeared mainly on the cell membranes and somatodendritic compartments of these ACs. For the cholinergic ACs, weak sst(5)-immunoreactivity was also observed in the processes terminating in the IPL. In contrast, no sst(5)-immunoreactivity was found in glycinergic AII ACs, stained by parvalbumin (PV). Furthermore, labeling for SRIF was co-localized with sst(5) in both dopaminergic and cholinergic ACs. These results suggest that sst(5) may serve as an autoreceptor or conventional receptor in retinal ACs.
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PMID:Expression of somatostatin receptor subtype 5 in rat retinal amacrine cells. 1715 33


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