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)

The distribution and morphology of neurons containing the dopamine- and cyclic AMP-regulated phosphoprotein, DARPP-32, were investigated in the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (CeA). DARPP-32 immunoreactive neurons are numerous in both regions, but are restricted to the lateral dorsal and the lateral juxtacapsular subdivisions of the BST, and the central lateral and lateral capsular subdivisions of the CeA. Immunoreactive neurons in the lateral dorsal BST, and the central lateral and lateral capsular CeA are similar morphologically, while those in the juxtacapsular BST appear to be a subpopulation of striatal medium-sized spiny neurons. The distribution of DARPP-32 immunoreactive neurons in the BST and CeA overlaps considerably with axonal plexuses containing tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP). These studies provide further evidence of the close relationship between the CeA and BST, and also provide anatomical evidence for possible interactions between neurotransmitters, neuropeptides, and phosphoproteins.
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PMID:Localization of DARPP-32 immunoreactive neurons in the bed nucleus of the stria terminalis and central nucleus of the amygdala: co-distribution with axons containing tyrosine hydroxylase, vasoactive intestinal polypeptide, and calcitonin gene-related peptide. 197 Dec 24

Tyrosine hydroxylase-like, dopamine- and cyclic AMP-regulated phosphoprotein (Mr = 32,000)-like and enkephalin-like immunoreactive profiles and their codistribution have been evaluated at three rostrocaudal levels of the rat neostriatum by means of a computer-assisted morphometrical method, which allows an objective definition of high density/intensity patches using specific antibodies in combination with the peroxidase-antiperoxidase technique. Our results show that both tyrosine hydroxylase-like, dopamine- and cyclic AMP-regulated phosphoprotein-like and enkephalin-like profiles are organized in patches in the rat neostriatum. In the marginal zone, the tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches both occupied a large part of the total area. Moreover, in this zone, these putative markers for pre- and postsynaptic elements of dopaminergic synapses also showed a complete spatial overlap. In contrast, the enkephalin-like immunoreactive patches in the marginal zone occupied a smaller area, and showed only an incomplete, albeit significant overlap with the tyrosine hydroxylase-like immunoreactive/dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive system. In the central zone, tyrosine hydroxylase-like immunoreactive, dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive and enkephalin-like immunoreactive patches occupied a much smaller part of the total area than did those in the marginal zone. Within the central zone, enkephalin-like immunoreactive patches occupied a significantly larger area than did the tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches. No consistent pattern of overlap between the three different staining patterns could be seen in the central zone, probably due to the small, inconsistent size of the patches. Trend analysis showed a consistent trend of more tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches in the dorsal than in the ventral striatum, and a trend of more enkephalin-like immunoreactive patches in the rostral than in the caudal striatum. Our data thus demonstrate that, by using computer-assisted morphometrical techniques, it is possible to describe a non-homogenous but overlapping distribution of tyrosine hydroxylase-like immunoreactive and dopamine- and cyclic AMP-regulated phosphoprotein-like immunoreactive patches in the rat neostriatum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Morphometrical evidence for a complex organization of tyrosine hydroxylase-, enkephalin- and DARPP-32-like immunoreactive patches and their codistribution at three rostrocaudal levels in the rat neostriatum. 290 56

By means of semiquantitative immunocytochemistry, possible age-related changes in dopamine and cyclic AMP-regulated phosphoprotein mr 32 (DARPP-32) and glial fibrillary acidic protein (GFAP) immunoreactivities (IR) were investigated in tanycytes of the arcuate nucleus. These two markers showed opposite changes during aging. DARPP-32 IR decreased by around 70%, whereas GFAP IR increased by around 300% in 24-month-old vs. 3-month-old rats. These changes were accompanied by a progressive loss in the number of tanycytes, measured by counting of their long processes in the arcuate nucleus. No significant age-related change was observed either in GFAP IR in astrocytic populations of the mediobasal hypothalamus or in tyrosine hydroxylase IR in dopaminergic neurons of the dorsal arcuate nucleus. These observations indicate that the tanycytic population of the arcuate nucleus undergoes important modifications during aging, which include cell loss, impairment in the intracellular signalling cascade linked to DARPP-32, and hypertrophy. These changes may be related to the alterations in the neuroendocrine systems known to occur during aging.
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PMID:Age-related alterations in tanycytes of the mediobasal hypothalamus of the male rat. 772 39

Basic parameters which are crucial for the survival of human embryonic striatal grafts need to be investigated before initiating clinical trials in Huntington's disease. In order to define the dissection of human striatal-donor tissue which gives rise to the largest amount of striatal neurons after intrastriatal transplantation, we studied the lateral and medial ganglionic eminences of embryonic striatal primordia obtained from human embryos sized 17-30 mm in crown-to-rump length (corresponding to Carnegie stages 18-23). Anatomical landmarks that demarcated the lateral and medial ganglionic eminences from each other were present only in embryos with 20 mm crown-to-rump length or larger. In monolayer cultures, the lateral ganglionic eminence gave rise to a six-fold higher yield of dopamine- and cyclic AMP-regulated phosphoprotein 32-immunoreactive striatal neurons as compared to the medial ganglionic eminence. We also xenografted the lateral and medial ganglionic eminences from five embryos sized 21-30 mm in crown-to-rump length to the ibotenate lesioned striatum of immunosuppressed rats. The grafts were evaluated with respect to general morphology, survival and integration using (immuno-) histochemical stains for acetylcholinesterase/Cresyl Violet, nicotinamide adenine dinucleotide phosphate-diaphorase, dopamine- and cyclic AMP-regulated phosphoprotein-32, tyrosine hydroxylase and calbindin-D28KD. As assessed 9-25 weeks after implantation, 13 out of 16 and 8 out of 13 grafts, in the groups grafted with the medial and lateral ganglionic eminences, respectively, had survived. Previous studies with rat donor tissue have indicated that the functional efficacy of striatal grafts is related to the development of striatal-specific P-zone regions and that these are enriched in transplants derived from the lateral as opposed to the medial ganglionic eminence. Also in the human striatal xenografts of the present study, P-zones appeared more abundant when the donor tissue was derived from the lateral ganglionic eminence. However, the proportion of graft tissue that expressed P-zone properties was always very low (at most 30%) and never approached the 80-90% previously observed in transplants of rat lateral ganglionic eminence. We conclude that the relative yield of striatal neurons in grafts of the human embryonic striatal primordium has to be improved before neural transplantation should be applied in patients with Huntington's disease.
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PMID:Phenotypic development of the human embryonic striatal primordium: a study of cultured and grafted neurons from the lateral and medial ganglionic eminences. 878 40

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.
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PMID:Evidence for aspartate-immunoreactive neurons in the neostriatum of the rat: modulation by the mesencephalic dopamine pathway via D1-subtype of receptor. 884 77

In the present study, we have characterized aspects of integration, growth and phenotypic differentiation of embryonic grafts derived from the selective dissection of either the lateral or medial portion of the ganglionic eminences of the rodent forebrain. Donor tissues were derived from embryonic day 15 rat, or embryonic day 14 mouse embryos, and injected, as single cell suspensions into the striatum or substantia nigra of adult rats previously subjected to an intrastriatal ibotenic acid lesion. Two to six weeks following grafting, immunocytochemical detection of DARPP-32, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein, was used to identify areas with a striatum-like phenotype within both the intrastriatal and the intranigral grafts. It was thus revealed that all the lateral ganglionic eminence grafts, irrespective of their placement, were dominated by striatum-like tissue (up to 90% of the total graft volume), while the medial ganglionic eminence transplants were only sparsely positive (< 10% of the total graft volume). These striatum-like regions of the grafts were selectively innervated by tyrosine hydroxylase immunopositive fibres from the host substantia nigra. Furthermore, axons derived from the lateral ganglionic eminence mouse grafts placed in the striatum, as detected by the mouse-specific neuronal marker M6, showed a more extensive and directed outgrowth towards the globus pallidus when compared to fibres emanating from the medial ganglionic eminence grafts. Mouse lateral and medial ganglionic eminence grafts placed into the substantia nigra exhibited similar fibre outgrowth patterns; both types of grafts thus innervated the substantia nigra-pars reticulata and extended axons into the cerebral peduncle. These results show that DARPP-32-positive striatal projection neurons are derived, for the most part, from the lateral ganglionic eminence and that the restricted lateral ganglionic eminence dissection provides a more optimal source of striatal tissue for grafting in the rat Huntington model.
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PMID:Projection neurons in fetal striatal transplants are predominantly derived from the lateral ganglionic eminence. 884 5

Addition of embryonic striatal tissue, usually as a combination of the lateral and medial ganglionic eminences, to intrastriatal mesencephalic grafts has previously been reported to enhance recovery of drug-induced rotational behavior in the host and to modify axonal fiber outgrowth from the grafted dopaminergic neurons. This study investigated the effects of adding (cografting) either lateral or medial ganglionic eminence tissue to embryonic mesencephalic grafts implanted intrastriatally, in rats with unilateral 6-hydroxydopamine lesions. The cografts did not exhibit increased survival or cell size of dopaminergic neurons when compared to transplants of mesencephalic tissue alone. Neither did recipients of cografts exhibit any enhancement of graft-induced recovery of function, when tested for drug-induced rotational behavior or forelimb function in the staircase test. However, cografts containing lateral ganglionic eminence displayed patches of dense tyrosine hydroxylase-immunoreactive fibers within the graft tissue. These patches largely coincided with patches in adjacent stained sections, which were rich in immunostaining for the striatal-specific marker dopamine- and cyclic AMP-regulated phosphoprotein-32 (DARPP-32). Such patches were not present in rats receiving cografts containing medial ganglionic eminence or mesencephalic tissue alone. Thus, it seems that the grafted dopaminergic neurons preferentially grow into the areas of the transplants containing lateral ganglionic eminence tissue. In summary, the results suggest that embryonic lateral ganglionic eminence exerts trophic effects on the outgrowth of dopaminergic axons, but does not enhance the behavioral effects of grafted dopaminergic neurons.
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PMID:Addition of lateral ganglionic eminence to rat mesencephalic grafts affects fiber outgrowth but does not enhance function. 917 Nov 60

The effects of the stage of donor embryos on the survival of grafts from different neuronal cell types have been well documented. Indeed, this parameter has been shown to be highly important in the survival and function of transplants of various tissues of the CNS. However this question has not been addressed in grafts of embryonic striatal tissue transplanted into animal models of Huntington's disease. In this study, rats which had received a unilateral ibotenic acid lesion in the dorsal striatum received grafts from a standard dissection of embryonic striatal primordium taken from donors of embryonic stage either E14, E16, E17 or E19 days. Three months after transplantation six rats from each group were killed for analysis of graft survival and morphology. The remaining animals in each group were killed between 10 and 14 months after grafting. Graft morphology was detected using a range of markers including: acetylcholinesterase and Cresyl Violet, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), tyrosine hydroxylase and striatally-enriched phosphatase. All the grafts from different donor stages survived well at both time-points and Cresyl Violet staining indicated neuronal cell types spread throughout the grafts. The transplants were seen to have a characteristic "patchy" appearance with areas of dense AChE activity and DARPP-32 immunopositivity interspersed with areas of much lighter expression. These areas also co-localized consistently with striatally-enriched phosphatase and tyrosine hydroxylase expression, indicating that they comprised the striatal-like compartment of the graft (the so called P zones, containing cells of the mature striatum), and receiving specific afferent input from the host dopaminergic system. There was no significant difference in total graft volume, when comparing individual groups at both time-points from grafting. However, when comparing the volume of the P zones, the striatal primordium from the youngest donor stages (E14 and E16) produced grafts with a significantly higher proportion of striatal-like tissue. Therefore, in order to increase the proportion of striatal tissue within these grafts, tissue from younger embryonic donors should be used. This has important implications in the application of this model towards clinical trials in Huntington's disease.
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PMID:The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. I. Morphological characteristics. 921 34

The nigrostriatal and mesolimbic systems of the rat were reconstructed using an organotypic culture model, whereby neonatal brain tissue was grown in vitro for approximately one month. The nigrostriatal system comprised of tissue from the substantia nigra, the dorsal striatum and the frontoparietal cortex, while the mesolimbic system included the ventral tegmental area, ventral striatum (including the fundus striati, accumbens nucleus, olfactory tubercle, lateral septum, ventral pallidum and piriform cortex) and cingulate cortex. These regions were also cultured alone or in pairs. The cultures were monitored in vitro, and after one month fixed in a formalin-picric acid solution, and processed for immunohistochemistry using antibodies raised against tyrosine hydroxylase, nitric oxide synthase, preprocholecystokinin, glutamate decarboxylase, neuropeptide Y, dopamine- and cyclic AMP-regulated phosphoprotein-32 and glial fibrillary acidic protein. The tissue survived in single, double or triple cultures, although differences were found depending upon the source and combination of cultured region. Neurons had localization and shape as in vivo. Local networks were especially prominent in the mesencephalon, where both tyrosine hydroxylase-positive axons spread from the "substantia nigra" to the rest of the tissue, and where nitric oxide synthase-positive networks also surrounded tyrosine hydroxylase-positive neurons. Glutamate decarboxylase-positive nerve terminals formed dense networks around tyrosine hydroxylase-positive neurons. In the striatum, nitric oxide synthase and dopamine- and cyclic AMP-regulated phosphoprotein-32 neurons were surrounded by tyrosine hydroxylase-positive nerve terminals. The nigral and ventral tegmental area dopamine neurons projected to striatal and cortical structures, but the projection from the ventral tegmental area to the cingulate cortex was more prominent. With regard to co-existence, preprochole-cystokinin-like immunoreactivities was found in many tyrosine hydroxylase-positive neurons and neuropeptide Y- and nitric oxide synthase-like immunoreactivity co-existed in striatal and cortical tissues. In general terms, the chemical neuroanatomy in the cultures was similar to that described earlier in vivo. Nitric oxide synthase staining was particularly intense. Taken together, the organotypic model captures many of the morphological and neurochemical features seen in vivo, providing a valuable model for studying neurocircuitries of the brain in detail, where 'normal' and 'pathological' conditions can be simulated.
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PMID:Neurocircuitries of the basal ganglia studied in organotypic cultures: focus on tyrosine hydroxylase, nitric oxide synthase and neuropeptide immunocytochemistry. 1062 53

The anatomy of the inferior-collicular complex of the barn owl, situated below the fourth ventricle in the tectal lobe, was studied by determining the distribution of antigens with antibodies directed against tyrosine hydroxylase, gamma-aminobutyric acid (GABA)(Abeta), dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), calretinin, and calbindin. Additionally, the somata were stained with cresyl violet, and fibers were marked according to the Gallyas procedure. These markers were chosen to allow for an easy delineation of the boundaries between the subnuclei of the inferior colliculus. We could discriminate eight structures that belong to the three subnuclei of the inferior colliculus [the central nucleus (ICC), the superficial nucleus (ICS), the external nucleus (ICX)] and to the optic tectum. Periventricular tectal layers 15a and 15b stained well with all the antibodies used. The ICS, embedded in tectal layer 15a, may be divided into a dorsal and a ventral lamina. It does not have direct contact with the other nuclei of the inferior colliculus. The border between tectal layer 15a and ICX was well marked by all antibodies, but less so in Gallyas and cresyl violet stains. The ICC consists of a core and a medial and lateral shell. The core was clearly demarcated with antibodies against calretinin and calbindin. The border between the lateral shell and the ICX was marked less well than the borders between ICX and 15a, but the somata were much more darkly labeled with the DARPP-32 antibody in ICX than in the lateral shell of ICC. None of the markers delineated the border between the medial and lateral shell of ICC.
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PMID:Anatomical markers for the subdivisions of the barn owl's inferior-collicular complex and adjacent peri- and subventricular structures. 1292 22


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