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)

Neuronal transplantation is an approach that can be exploited to study the development of the human central nervous system as well as being used in attempts to restore neurological function. In the present study, we have examined cellular events that appear to precede the development of dopamine nerve fiber extension by neurons from the human fetal ventral mesencephalon. These cellular events were examined using neuronal cell suspensions from human fetal ventral mesencephalic tissue (gestational ages 7-10 weeks) transplanted into the striatum of unilaterally lesioned 6-hydroxydopamine (6-OHDA) rats. Animals were sacrificed for immunohistochemistry 9-10 weeks after the transplantation prior to the manifestation of behavioral recovery. Histological analysis revealed tyrosine hydroxylase (TH) immunoreactive neurons in the grafts. The majority of these neurons had very short TH positive processes (60-70 microns), indicating that the maturation of grafted dopaminergic neurons was still incomplete. Immunostaining for the human specific intermediate neurofilament (hNF, clone: BF-10) showed dense neuronal fibers in the grafts. These fibers extended deeper into the host brain than the TH positive neuronal processes. The whole striatum, particularly the medial part of the striatum, exhibited long NF positive processes. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed fine astrocytic processes inside the grafts, which were clearly different from host reactive glial cells surrounding the grafts. These graft-derived glial processes tended to extend into the host brain deeper than the TH positive neuronal processes from the grafts. These early histological findings of the grafted human fetal ventral mesencephalon suggest that the graft-derived NF positive neuronal processes, as well as the glial processes, radiate from the grafted tissue and extend into the host brain prior to the extension of TH positive processes. These results further suggest that human-to-rat xenografts can be used to study the neural development of human fetal brain tissue.
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PMID:Development of human fetal ventral mesencephalic grafts in rats with 6-OHDA lesions of the nigrostriatal pathway. 775 3

Retrograde tract-tracing techniques were used to investigate whether catecholaminergic neurons in the ventrolateral medulla (VLM) send collateral axonal projections to both central nuclei of the amygdala (ACe) in the rat. Rhodamine-labelled latex microspheres or fluorogold (2%) were microinjected into the region of either the right or left ACe. After a survival period of 10-12 days, the rats were sacrificed and transverse sections of the brainstem were processed immunohistochemically for the identification of cell bodies containing the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) or phenylethanolamine-N-methyltransferase (PNMT). Neuronal perikarya containing the retrogradely transported tracers were observed throughout the rostrocaudal extent of VLM, bilaterally. Approximately 10% of the retrogradely labelled neurons were observed to contain both retrograde tracers. The majority (79 +/- 6.8%) of these double labelled neurons were located within the caudal VLM and their number decreased rostrally. In addition, the proportion of double labelled neurons to single labelled neurons in VLM decreased rostrally; approximately 11% in the caudal VLM and 6% in the rostral VLM. Furthermore, approximately 21% of all VLM neurons that projected to ACe were found to be catecholaminergic: 75% of these were immunoreactive to TH and 25% to PNMT. However, no neurons were found in VLM that contained both retrograde tracers and immunoreactivity to TH or PNMT. These data demonstrate that axons originating from non-catecholaminergic neurons in VLM bifurcate to innervate ACe bilaterally. Although the function of these VLM neurons that project to both ACe is not known, they may be the anatomical substrate by which VLM neurons relay simultaneously autonomic and/or visceral sensory information to influence the activity of ACe.
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PMID:Collateral axonal projections from ventrolateral medullary non-catecholaminergic neurons to central nucleus of the amygdala. 787 22

Grafts of fetal neural tissue, rich in dopamine (DA) neurons, have previously been shown to improve the symptoms of parkinsonism, both in humans and in animal models. In order to circumvent some of the problems associated with cell transplant therapy, such as the limited availability of transplant tissue, we have established a reaggregate (three-dimensional) tissue culture system that can be used to proliferate normal mammalian neuronal precursors. We demonstrate the in vitro growth of DA-neuronal precursors derived from embryonic porcine ventral mesencephalon, Carnegie stages 15-18. Cultures of DA-neuronal precursors were maintained in F12 medium supplemented with Chang C Supplement for 5 days and switched to serum-free N2 medium for an additional 10 days. Cultures labeled with tritiated thymidine on Days 5-7 in vitro revealed that 43.5% of the DA neurons had incorporated the label, indicative of cell division. Histological examination of the cultured cells demonstrated rosette-like structures, similar to developing neuroepithelium in vivo. Neuronal maturation in vitro was stimulated by dibutyryl cyclic AMP (dbcAMP). Exposure to 5 mM dbcAMP for 7 days stimulated tyrosine hydroxylase (TH), neuron-specific enolase, and 200-kDa neurofilament accumulation three- to sixfold above control levels. After 15 days in vitro, cultured cells reversed amphetamine-induced rotation when grafted into the striata of hemiparkinsonian rats. Successful transplants of cultured neurons were dependent upon a minimum density of DA neurons within the graft (greater than 100 DA neurons/mm3 of graft volume). Data suggest that the percentage of TH neurons can be increased about threefold by culturing the aggregates in tyrosine-free medium, which selects for TH-positive cells. The ability to cultivate mammalian neuronal precursor cells in vitro may eventually make graft therapy a more practical approach to treatment of neurological diseases.
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PMID:A model three-dimensional culture system for mammalian dopaminergic precursor cells: application for functional intracerebral transplantation. 790 68

Dopaminergic (DA) cells of the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) display differences in their topography, biochemistry and susceptibility to pathological processes. Neuronal dopamine concentration is regulated in large part by tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis, and by the dopamine reuptake system. In the present study, TH protein, TH mRNA and dopamine membrane transporter (DAT) mRNA were quantified at cellular level in 4 arbitrary subregions of the rat ventral mesencephalon (lateral, middle, medial SNC and VTA), using in situ hybridization and immunoautoradiography. The distribution of labelling for TH protein and TH mRNA was almost superimposable and close to that of DAT mRNA in mesencephalic neurons. Lower values of cellular expression in TH protein, TH mRNA and DAT mRNA were observed in the lateral part of the SNC compared to the other subregions. TH and DAT expression were correlated in SNC but not in VTA. Indeed DA cells in this region expressed low levels of DAT mRNA in comparison to the middle and medial SNC. These results suggest a heterogeneity of DA metabolism among populations of mesencephalic cells. The relative lower expression of the DAT gene in VTA neurons suggests a less efficient dopamine reuptake capacity, which may partly account for the relative sparing of the mesolimbic system reported in Parkinson's disease and MPTP-treated animals.
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PMID:Differential expression of tyrosine hydroxylase and membrane dopamine transporter genes in subpopulations of dopaminergic neurons of the rat mesencephalon. 791 4

Parkinson's disease is characterized by the degeneration of melanized dopaminergic neurons of the substantia nigra. The functional capacity of the surviving dopaminergic neurons is affected, as suggested by the subnormal levels of tyrosine hydroxylase messenger RNA and protein found in the remaining cells. The reduced expression of tyrosine hydroxylase may be due to either the evolving neurodegenerative process or its downregulation, possibly secondary to chronic levodopa treatment. The cellular content of tyrosine hydroxylase was determined in the mesencephalon from 16 Macaca fascicularis monkeys, using a semiquantitative immunocytochemical method. Thirteen monkeys were rendered parkinsonian by weekly intravenous injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 2 (subacute treatment) or 20 (chronic treatment) weeks. Three of the monkeys received levodopa and 3 others received GM1 ganglioside. The loss of dopaminergic neurons in the mesencephalon of the MPTP-intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance. After both subacute and chronic treatment, the cellular content of tyrosine hydroxylase was reduced by 40% in the surviving neurons of the lesioned substantia nigra, but by less in the other mesencephalic dopaminergic regions. Neuronal survival and tyrosine hydroxylase content in monkeys that had received levodopa were not significantly different. The cellular content of tyrosine hydroxylase was increased in the substantia nigra of the monkeys that received GM1 ganglioside injections. The results show that the decreased expression of tyrosine hydroxylase found in nigral dopaminergic neurons after partial degeneration of the mesostriatal dopaminergic system is not influenced by levodopa treatment and is partially reversed by GM1 ganglioside administration.
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PMID:Decreased tyrosine hydroxylase content in the dopaminergic neurons of MPTP-intoxicated monkeys: effect of levodopa and GM1 ganglioside therapy. 791 99

We have previously found in rat superior cervical ganglion that there is a fall in neuron numbers and in cellular neuropeptide Y (NPY) immunoreactivity over the first year of life. In this study, we have used computerized image analysis to quantitate changes in neuron size, numbers and immunoreactivity for neuron-specific enolase (NSE), tyrosine hydroxylase (TH) and NPY in this ganglion between 1 and 85 weeks of age. Neuronal cytoplasmic area increased between 1 and 11 weeks and then remained stable until after 67 weeks, when there was a further increase in size of both NPY-positive and NPY-negative cells. Numbers of NPY-positive cells, but not those of NPY-negative cells, fell between 11 and 30 weeks. Both populations were stable after this time. Neuronal levels of NSE and TH remained constant, but levels of NPY fell between 58 and 67 weeks. These results indicate that changes in adult neuronal size, numbers and neurochemistry are independent phenomena. The increase in cell size and the fall in NPY after 58 weeks correspond to the time of withdrawal of some preganglionic inputs and may be responses to this event. By contrast, the decrease in NPY-positive cell numbers occurs some months before this time.
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PMID:Morphometric and neurochemical changes in rat superior cervical ganglion during growth and adulthood. 809 86

Pineal cells of the embryonic quail are multipotent stem cells which are able to differentiate in vitro into pigmented epithelial cells, lens cells and skeletal muscle fibers. Neuronal expression was added in this study in the repertory of differentiating potency of pineal cells. We used immunohistochemical methods to characterize neuronal properties with antibodies against serotonin, GABA, tyrosine hydroxylase and neuron-specific antigen (HPC-1) in addition to the enzyme histochemistry for acetylcholinesterase activity. Cells in the culture were found to be positively stained with these methods, suggesting that embryonic pineal cells are neuropotent to differentiate various types of neuronal cells. We have studied the culture conditions which favor increment of neuronal cells with extension of neuritic processes, and we have found that neuronal cells are maintained for quite a long period under suppressive conditions of DNA synthesis and under the effect of basic fibroblast growth factor (FGF). Suppression of DNA synthesis was achieved by the addition of aphidicolin, an inhibitor of DNA polymerase alpha, in the medium. Time lapse videograph revealed two different cell types participated in neurogenesis; a minor population of small round cells and a major one of flat epithelial cells. Since embryonic quail pineal cells have been shown to differentiate into two types of photoreceptors, the present results show wider retinal potency of cell differentiation by embryonic pineal cells. The cessation of DNA synthesis as well as growth factor(s) may be positively involved in the mechanisms of determination and differentiation of pineal neurons.
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PMID:Retinal differentiation from multipotential pineal cells of the embryonic quail. 813 21

Nigrostriatal dopaminergic neurons play an essential role in the central regulation of motor functions. These functions are initiated through the release of dopamine from axon terminals in the striatum or from dendrites in the substantia nigra (SN) and are terminated by the reuptake of dopamine by the sodium- and chloride-dependent dopamine transporter (DAT). DAT also can transport dopamine neurotoxins and has been implicated in the selective vulnerability of nigrostriatal dopaminergic neurons in major models of Parkinson's disease. We have used electron microscopic immunocytochemistry with an N-terminal domain anti-peptide antibody to examine the subcellular distribution of DAT in the rat SN and dorsolateral striatum. In the SN, immunogold labeling for DAT was localized to cytoplasmic surfaces of plasma membranes and smooth endoplasmic reticulum of dendrites and dendritic spines, few of which contained synaptic vesicles. Neuronal perikarya in the SN contained immunogold-labeled pleomorphic electron-lucent tubulovesicles but showed immunolabeling of plasma membranes only rarely. Axon terminals in the striatum contained extensive immunogold labeling of cytoplasmic surfaces of plasma membranes near aggregates of synaptic vesicles and less frequent labeling of intervaricose segments of plasma membrane or small electron-lucent vesicles. In sections dually labeled for DAT and the catecholamine-synthesizing enzyme tyrosine hydroxylase, both markers were colocalized in most profiles in the SN and striatum. These findings support the proposed topological model for DAT and suggest that this transporter is strategically located to facilitate uptake of dopamine and neurotoxins into distal dendritic and axonal processes of nigrostriatal dopaminergic neurons.
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PMID:The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons. 855 28

Neuronal activity may lead to long lasting changes in cell phenotype through induction of genes such as c-fos which encode transcriptional regulatory factors. Odor-activated olfactory bulb cells exhibit increases in c-fos mRNA expression. The present study examined whether odor stimulation of awake rats also leads to increases in Fos protein in these cells. The phenotype of Fos-immunoreactive cells was partially characterized using double-immunoperoxidase staining. Odor exposure increased Fos-immunoreactivity (IR) in specific sets of olfactory bulb neurons. Fos-IR was not co-localized with IR for glial fibrillary acidic protein, but was co-localized with tyrosine hydroxylase (TH)-IR in a subpopulation of dopaminergic neurons, suggesting that bulbar TH expression may be regulated in part by a Fos mechanism.
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PMID:Odors increase Fos in olfactory bulb neurons including dopaminergic cells. 859 90

Two fundamental questions about neuron cell culture were addressed. Can one serum-free medium that was developed for optimum growth of hippocampal neurons support the growth of neurons from other regions of the brain? Is the region specific state of differentiation maintained in culture? To answer these questions, we isolated neurons from six other rat brain regions, placed them in culture in B27/Neurobasal defined medium, and analyzed their morphology and growth dependence on cell density after 4 days in culture. Neuronal identity was confirmed by immunostaining with antibodies to neurofilament 200. Neurons from each brain region maintained distinctive morphologies in culture in the virtual absence of glia. Cells isolated from embryonic day 18 cerebral cortex by digestion with papain showed the same high survival as hippocampal neurons, e.g., 70% survival for cells plated at 160/mm2. At this age and density, neurons from the septum showed slightly lower survival, 45%. Survival of dentate granule neurons from postnatal day four brains was 30-40%, significantly lower, and relatively independent of plating density. This suggests an absence of dependence on trophic factors or contact for dentate granule neurons. Growth of cerebellar granule neurons isolated from postnatal day 7, 8, or 9 brains in B27/Neurobasal was compared to growth in BME/10% serum. Viability in serum-free medium at 4 days was much better than that in serum, did not require KCl elevated to 25 mM, and occurred without substantial growth of glia. Cerebellar granule neurons plated at 1,280 cells/mm2 were maintained in culture for three weeks with 17% of the original cell density surviving. Survival of cells isolated from embryonic day 18 substantia nigra was 50% at 160 cells/mm2 after 4 days, similar to that of striatum, but slightly less than hippocampal neuron survival. The dopaminergic phenotype of the substantia nigral neurons was maintained over 2 weeks in culture as judged by immunoreactivity with antibodies to tyrosine hydroxylase. During this time, immunoreactivity was found in the processes as they grew out from the soma. Together, these studies suggest that B27/Neurobasal will be a useful medium for maintaining the differentiated growth of neurons from many brain regions. Potential applications of a common growth medium for different neurons are discussed.
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PMID:Serum-free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus. 860 Mar


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