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)

A population of tyrosine hydroxylase (TH)-containing neurons that is up-regulated after lesion of the nigrostriatal dopaminergic pathway has been described in the primate striatum. The goal of this study was to examine the morphology, synaptology, and chemical phenotype of these neurons and TH-immunoreactive (-ir) terminals in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys. TH-ir perikarya were small (10-12 microm), displayed nuclear invaginations, and received very few synaptic inputs. On the other hand, TH-containing dendrites were typically large in diameter (>1.0 microm) and received scarce synaptic innervation from putative excitatory and inhibitory terminals forming asymmetric and symmetric synapses, respectively. More than 70% of TH-positive intrastriatal cell bodies were found in the caudate nucleus and the precommissural putamen, considered as the associative functional territories of the primate striatum. Under 10% of these cells displayed calretinin immunoreactivity. TH-ir terminals rarely formed clear synaptic contacts, except for a few that established asymmetric axodendritic synapses. Almost two-thirds of TH-containing boutons displayed gamma-aminobutyric acid (GABA) immunoreactivity in the striatum of parkinsonian monkeys, whereas under 5% did so in the normal striatum. These findings provide strong support for the existence of a population of putative catecholaminergic interneurons in the associative territory of the striatum in parkinsonian monkeys. Their sparse synaptic innervation raises interesting issues regarding synaptic and nonsynaptic mechanisms involved in the regulation and integration of these neurons in the striatal microcircuitry. Finally, the coexpression of GABA in TH-positive terminals in the striatum of dopamine-depleted monkeys suggests dramatic neurochemical changes in the catecholaminergic modulation of striatal activity in Parkinson's disease.
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PMID:Synaptic microcircuitry of tyrosine hydroxylase-containing neurons and terminals in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. 1648 90

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

The present study investigated the prenatal development of the cyto- and chemoarchitecture of the human nucleus of the solitary tract from 9 to 35 weeks, by using Nissl staining and immunoreactivity to calbindin, calretinin, tyrosine hydroxylase and GAP-43. The nucleus began to gain heterogeneity and show different subnuclei as early as 13 weeks, and approached cytoarchitectural maturation from 21 to 25 weeks. The subnuclear division pattern observed in the fetal nucleus of the solitary tract at 25 weeks was very similar to that of the adult. Neurons immunoreactive to calbindin first appeared in the medial gastrointestinal area of the nucleus at 13 weeks, particularly within a putative gelatinosus subnucleus, while calretinin immunoreactivity during fetal life suggested the possible presence of a central subnucleus. Tyrosine hydroxylase immunoreactive neurons were seen in the medial subdivisions of the nucleus of the solitary tract as early as 13 weeks, but the population continued to increase until 25 weeks. Strong GAP-43 immunoreactivity was also present in the nucleus of the solitary tract at 13 weeks, especially in the dorsolateral and commissural subnuclei, while at 21 weeks there was a significant decline of GAP-43 expression. Results from the chemoarchitectural study showed that the human nucleus of the solitary tract expressed various neurochemical substances at an early developmental age (13 weeks), even before cellular and neuropil maturation was fully attained. Expression of these factors may play an important role in establishment and integration of viscerosensory function in the nucleus.
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PMID:Development of the human nucleus of the solitary tract: a cyto- and chemoarchitectural study. 1672 Jan 6

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

The neurochemistry of the retina of the larval and postmetamorphic sea lamprey was studied via immunocytochemistry using antibodies directed against the major candidate neurotransmitters [glutamate, glycine, gamma-aminobutyric acid (GABA), aspartate, dopamine, serotonin] and the neurotransmitter-synthesizing enzyme tyrosine hydroxylase. Immunoreactivity to rod opsin and calretinin was also used to distinguish some retinal cells. Two retinal regions are present in larvae: the central retina, with opsin-immunoreactive photoreceptors, and the lateral retina, which lacks photoreceptors and is mainly neuroblastic. We observed calretinin-immunostained ganglion cells in both retinal regions; immunolabeled bipolar cells were detected in the central retina only. Glutamate immunoreactivity was present in photoreceptors, ganglion cells, and bipolar cells. Faint to moderate glycine immunostaining was observed in photoreceptors and some cells of the ganglion cell/inner plexiform layer. No GABA-immunolabeled perikarya were observed. GABA-immunoreactive centrifugal fibers were present in the central and lateral retina. These centrifugal fibers contacted glutamate-immunostained ganglion cells. No aspartate, serotonin, dopamine, or TH immunoreactivity was observed in larvae, whereas these molecules, as well as GABA, glycine, and glutamate, were detected in neurons of the retina of recently transformed lamprey. Immunoreactivity to GABA was observed in outer horizontal cells, some bipolar cells, and numerous amacrine cells, whereas immunoreactivity to glycine was found in amacrine cells and interplexiform cells. Dopamine and serotonin immunoreactivity was found in scattered amacrine cells. Amacrine and horizontal cells did not express classical neurotransmitters (with the possible exception of glycine) during larval life, so transmitter-expressing cells of the larval retina appear to participate only in the vertical processing pathway.
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PMID:Presence of glutamate, glycine, and gamma-aminobutyric acid in the retina of the larval sea lamprey: comparative immunohistochemical study of classical neurotransmitters in larval and postmetamorphic retinas. 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

The subventricular zone (SVZ) of the lateral ventricle develops from residual progenitors of the embryonic lateral ganglionic eminence (LGE) and maintains neurogenic activity throughout life. Precursors from LGE/SVZ migrate to the olfactory bulb (OB) where they differentiate into local interneurons, principally in the granule layer and glomerular layer (GL). By in situ dye labeling, we show that neonatal and adult SVZ progenitors differentially contribute to neurochemically distinct types of periglomerular interneurons in the GL. Namely, calbindin-positive periglomerular cells are preferentially generated during early life, whereas calretinin- and tyrosine hydroxylase-expressing neurons are mainly produced at later ages. Furthermore, homochronic/heterochronic transplantation demonstrates that progenitor cells isolated from the LGE or SVZ at different stages (embryonic day 15 and postnatal days 2 and 30) engraft into the SVZ of neonatal or adult mice, migrate to the OB, and differentiate into local interneurons, including granule and periglomerular cells as well as other types of interneurons. The total number of integrated cells and the relative proportion of granule or periglomerular neurons change, according to the donor age, whereas they are weakly influenced by the recipient age. Analysis of the neurochemical phenotypes acquired by transplanted cells in the GL shows that donor cells of different ages also differentiate according to their origin, regardless of the host age. This suggests that progenitor cells at different ontogenetic stages are intrinsically directed toward specific lineages. Neurogenic processes occurring during development and in adult OB are not equivalent and produce different types of periglomerular interneurons as a consequence of intrinsic properties of the SVZ progenitors.
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PMID:Generation of distinct types of periglomerular olfactory bulb interneurons during development and in adult mice: implication for intrinsic properties of the subventricular zone progenitor population. 1723 97

In order to investigate epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy (DRPLA), we immunohistochemically examined the expression of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex in autopsy cases. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 cases of juvenile and 2 cases of early adult types with progressive myoclonus epilepsy (PME), 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to tyrosine hydroxylase, tryptophan hydroxylase, substance P, methionine-enkephalin, parvalbumin, calbindin-D28K, calretinin, and excitatory amino acid transporters. Although the size of the tegmentum was small, we failed to find any PME-specific brainstem changes in the expression of neurotransmitters, neuropeptides and calcium-binding proteins. The number of interneurons immunoreactive for calbindin-D28K and parvalbumin, markers of GABAergic inhibitory interneurons, were reduced throughout the cerebral cortex, but there was no significant difference in the density of immunoreactive neurons between DRPLA patients of each type. The expression of glutamate transporters was comparatively spared. The current study revealed an absence of PME-specific brainstem lesions and indicated a possible involvement of the reduced GABAergic interneurons in the cerebral cortex in formation of PME in DRPLA.
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PMID:Neuropathological analysis of the brainstem and cerebral cortex lesions on epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy. 1730 19

Olfactory sensory information is processed and integrated by circuits within the olfactory bulb. Golgi morphology suggests the olfactory bulb contains several major neuronal classes. However, an increasingly diverse collection of neurochemical markers have been localized in subpopulations of olfactory bulb neurons. While the mouse is becoming the animal model of choice for olfactory research, little is known about the proportions of neurons expressing and coexpressing different neurochemical markers in this species. Here we characterize neuronal populations in the mouse main olfactory bulb, focusing on glomerular populations. Immunofluorescent labeling for: 1) calretinin, 2) calbindin D-28K (CB), 3) parvalbumin, 4) neurocalcin, 5) tyrosine hydroxylase (TH), 6) the 67-kDa isoform of GAD (GAD67), and 7) the neuronal marker NeuN was performed in mice expressing green fluorescent protein under the control of the glutamic acid decarboxylase 65kDa (GAD65) promoter. Using unbiased stereological cell counts we estimated the total numbers of cells and neurons in the bulb and the number and percentage of neurons expressing and coexpressing different neurochemical populations in each layer of the olfactory bulb. Use of a genetic label for GAD65 and immunohistochemistry for GAD67 identified a much larger percentage of GABAergic neurons in the glomerular layer (55% of all neurons) than previously recognized. Additionally, while many glomerular neurons expressing TH or CB coexpress GAD, the majority of these neurons preferentially express the GAD67 isoform. These data suggest that the chemospecific populations of neurons in glomeruli form distinct subpopulations and that GAD isoforms are preferentially regulated in different neurochemical cell types.
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PMID:Quantitative analysis of neuronal diversity in the mouse olfactory bulb. 1731 23


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