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)

The detailed morphology of the dopaminergic amacrine cell type has been characterized in the macaque monkey retina by intracellular injection of horseradish peroxidase (HRP). This cell type was recognized by its large soma in an in vitro, wholemount preparation of the retina stained with the fluorescent dye, acridine orange. HRP-fills revealed a large, sparsely branching, spiny dendritic tree and a number of extremely thin, axon-like processes that arose from the soma and proximal dendrites. The axon-like processes were studded with distinct varicosities and were traced for up to 3 mm beyond the dendritic tree. The true lengths of the axon-like processes were greater than 3 mm, however, because the HRP reaction product consistently diminished before an endpoint was reached. Both the dendrites and the axon-like processes were narrowly stratified close to the outer border of the inner plexiform layer, although in a few cases single axon-like processes projected into the outer nuclear and outer plexiform layers. The HRP-filled amacrines appeared equivalent to a subpopulation of neurons that are intensely immunoreactive for tyrosine hydroxylase (TH). TH-immunoreactive cells showed a nearly identical soma size and dendritic field size range, the same pattern of dendritic branching and spiny morphology, and also gave rise to distinct axon-like processes from both the soma and proximal dendrites. To test this correspondence more directly, the large acridine stained cells were injected with Lucifer Yellow and the retina was subsequently processed for TH immunoreactivity using diaminobenzidine as the chromagen. In all cases Lucifer Yellow injected cells also showed intense TH immunoreactivity. Spatial densities of the TH amacrine cells were therefore used to calculate coverage factors for the dendritic trees and for the axon-like components of the HRP-filled cells. The axon-like processes showed a coverage factor of at least 300, about 100 times that of the dendritic fields. This great overlap could be directly observed in TH-immunoreacted retinal wholemounts as a dense plexus of fine, varicose processes. The density of the TH plexus is greater than the density predicted from the lengths (1-3 mm) of the HRP-filled axon-like processes however, and suggests that the axon-like processes have an actual length of about 4-5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The dopaminergic amacrine cell. 197 92

To determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) alters the tyrosine hydroxylase (TH) immunoreactivity of murine dopaminergic retinal amacrine cells, 8-10-week-old C57BL/6J mice were treated with i.p. with saline or cumulative doses of MPTP ranging from 10 to 300 mg/kg. Paraformaldehyde-fixed retinal whole mounts and cross sections were examined using immunochemistry with a tyrosine hydroxylase (TH) or a choline acetyltransferase (ChAT) polyclonal antibody and an avidin-biotin peroxidase reaction. Both TH+ amacrines and ChAT+ retinal neurons showed somal and process morphology and distributions that were commensurate with previous studies of the same or several related species. At 20 days following the MPTP treatment, there was a loss of TH+ amacrines according to a logarithmic relationship relative to MPTP dosage. The loss ranged from 18 to 87% for the dosage range without any decrease in the numbers of ChAT+ neurons. The TH+ amacrines were deleted randomly from the retinas without any peripheral-central predilection. By 273 days after MPTP treatment, the number of TH+ amacrines had returned to values found for age-matched controls demonstrating that the loss of TH immunoreactivity was reversible and occurred without destruction of TH+ amacrines. Computer densitometry revealed that the MPTP-treated TH+ amacrines were divided into two distinct populations: one with normal TH immunodensity levels and a second with TH immunodensity levels below our detection capability. Increasing the MPTP dosage increased the proportion of TH amacrines in the second population. The transient and completely reversible disappearance in the number of TH+ amacrines: (1) appears to form the basis for the decreased concentrations of dopamine and the loss of catecholamine fluorescent neurons previously described for MPTP-treated mouse retinae; (2) may underlie the defects in the electroretinograms of MPTP-treated monkeys, and (3) may result as a response to neurite damage similarly to the alterations in protein synthesis in other central neurons following axonal damage.
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PMID:MPTP produces reversible disappearance of tyrosine hydroxylase-containing retinal amacrine cells. 198 Aug 39

Spinal cord transection was induced in 3 groups of cats. The gap was surgically reconstructed using a collagen matrix bridge (Group COL), collagen matrix + pedicled omentum graft (Group COM), or gelfoam (Group GEF). After a variable observation period, animals underwent distal cord horse-radish peroxidase (HRP) injections, somatosensory evoked potentials recordings and polarographic measurement of local spinal cord blood flow (1SCBF) using the hydrogen clearance technique. The cord tissue was removed for histologic and immunohistochemical analysis. Results showed retrograde HRP labelling of proximal segmental cord neurons and somatosensory evoked potentials were present in group COM but not in COL or GEF treated animals. Local SCBF was 66% and 87% higher in COM than COL or GEF animals respectively but this increase could be reversed if flow from the pedicled omentum was clamped-off. Histologic examination of cord tissue after 45 days revealed the presence of catecholaminergic axons distal to the transection site in COM but not COL or GEF groups. Moreover, after 90 days, the rate and density of tyrosine hydroxylase immunoreactive (TH-IR) axons was 10-fold higher in COM than COL group and this was accompanied by a proportionate increase in the vascular density between the two groups. GEF treated animals showed no regeneration of transected fibers and poor blood flow pattern. These findings indicate that the placement of a pedicled omentum on a collagen matrix bridge results in near restoration of normal SCBF to the reconstructed cord region and is associated with marked regeneration of axons below the lesion site.
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PMID:Collagen-omental graft in experimental spinal cord transection. 217 74

We examined whether autoradiographic localization of [125I]-antirabbit immunoglobulin (IgG) was suitable for light and electron microscopic detection of a rabbit antiserum to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), and whether autoradiographic and peroxidase labeling could be combined for simultaneous immunocytochemical identification of TH and neuropeptides in brain. Adult rat brains were fixed by aortic arch perfusion with acrolein and paraformaldehyde. Vibratome sections of the fixed tissues were incubated with various dilutions of TH antiserum followed by [125I]-secondary IgG. These sections were then directly processed for autoradiography or were incubated with rabbit antiserum to substance P (SP) or methionine [Met5]-enkephalin (ME). These latter sections were then processed by the peroxidase-antiperoxidase (PAP) or conjugated peroxidase methods followed by autoradiography. Exposure periods of 12-20 days for light microscopy or 90 days for electron microscopy yielded substantial accumulations of silver grains even at the highest (1:30,000) dilution of TH antiserum. At this dilution, immunoreactivity for TH was virtually nondetectable by PAP and conjugated peroxidase methods. The differential sensitivities of the autoradiographic versus peroxidase methods provided a means for separable identification of rabbit antiserum to TH and to SP or ME. Ultrastructural analysis of the catecholaminergic neurons in the medial nuclei of the solitary tract (NTS) showed selective cytoplasmic localization of silver grains for [125I]-labeling of TH in perikarya, dendrites, and terminals. Within single thin sections prepared for dual labeling, the peroxidase marker for SP and for ME was differentially localized with respect to autoradiographic labeling of TH.
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PMID:Autoradiographic detection of [125I]-secondary antiserum: a sensitive light and electron microscopic labeling method compatible with peroxidase immunocytochemistry for dual localization of neuronal antigens. 242 51

Dual labeling electron microscopic immunocytochemistry was used to investigate the cellular substrate for functional interactions between substance P (SP) and dopamine in the rat nucleus accumbens. Coronal vibratome sections from acrolein-fixed brains were sequentially processed for the localization of: (1) a rat monoclonal antiserum against SP identified by the peroxidase--anti-peroxidase immunocytochemical method, and (2) a rabbit polyclonal antiserum against tyrosine hydroxylase (TH) identified by immunoautoradiography. The monoclonal rat antiserum recognized principally SP, but also exhibited cross-reactivity with certain other tachykinins such as substance K. Terminals showing SP-like immunoreactivity (SPLI) were 0.2-1.5 microns in diameter and contained numerous small (30-40 nm), round vesicles; one or more large (80-150 nm), dense-core vesicles; and an occasional membrane-bound multivesicular body. From a total of 114 SP-labeled terminals that were quantitatively analyzed, 30.1% formed symmetric synapses with dendrites; whereas only 8% formed asymmetric junctions with dendritic spines. Terminals showing SPLI also occasionally formed junctions with dendrites receiving synaptic input from other terminals that were similarly labeled for the peptide or from terminals immunoautoradiographically labeled for TH. In contrast to the low frequency of postsynaptic relationships, 39.8% of the terminals containing SPLI showed close associations with other unlabeled or TH-labeled terminal or preterminal axons. The axonic contacts were characterized by equally spaced membranes that were not separated by glial processes. Within the terminals containing SPLI, vesicles were located near the axonic contacts; whereas vesicles in unlabeled terminals were located more distally with respect to these appositions. We conclude that in the rat nucleus accumbens SP or a closely related tachykinin subserves principally inhibitory functions at postsynaptic sites as indicated by the prominence of symmetric junctions. The abundance of axonic associations and sparsity of convergent input from TH- and SP-labeled terminals at closely spaced sites on dendrites supports the concepts that a SP-like tachykinin also may modulate the release of dopamine through direct or indirect presynaptic mechanisms. The possibility that there may be more extensive postsynaptic associations through convergence at widely spaced sites on common neurons is discussed.
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PMID:Substance P in the rat nucleus accumbens: ultrastructural localization in axon terminals and their relation to dopaminergic afferents. 245 97

The sequential application of the avidin-biotin-peroxidase complex technique was used to localize multiple tissue antigens on a single free floating section of rat brain. Sequential visualization of individual antigens was achieved by the silver-gold-intensified diaminobenzidine (DAB) in the first step, nickel-intensified DAB in the second step, and the DAB alone in the third step of the immunostain procedure. For the demonstration of this method, tyrosine hydroxylase (TH), corticotropin-releasing factor (CRF), and vasopressin (VAS) antisera were used. Sections from the hypothalamic paraventricular nucleus (PVN) of rats pretreated with colchicine were stained. Black TH containing cell bodies were clearly distinguished from blue stained CRF cells and from yellow stained VAS-containing cell bodies in the PVN on the 25-30 micron thick vibratome sections. The sequential immunostaining procedure presented here results in superior staining of multiple antigens as compared to that achieved by the sequential application of the peroxidase-antiperoxidase (PAP) technique.
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PMID:Light microscopic triple-colored immunohistochemical staining on the same vibratome section using the avidin-biotin-peroxidase complex technique. 245 9

The coexistence of immunoreactivities for glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and substance P (SP) was revealed in the hamster main olfactory bulb, using the peroxidase-antiperoxidase immunohistochemical method. Adjacent 40 micron thick Vibratome sections were incubated in different antisera and those cells which were bisected by the plane of sectioning were identified at the paired surfaces of two consecutive sections. The coexistence of the immunoreactivities for 1) TH and GAD, 2) TH and SP and 3) GAD and SP in the same cells could thus be determined by observing the immunoreactivity of the two halves of the cell incubated in two different antisera. About 70% of TH-like immunoreactive (TH-LI) neurons in the periglomerular region also contained GAD-like immunoreactivity, whereas about 45% of GAD-LI ones were also TH-like immunoreactive. Furthermore, almost all (more than 95%) of SP-LI neurons contained both GAD-like and TH-like immunoreactivities. These observations indicate that in the periglomerular region of the hamster main olfactory bulb, some neurons (about 9% of all neurons containing TH-like and/or GAD-like immunoreactivities) may contain three different categories of neuroactive substances, that is, amino acid (GABA), amine (dopamine) and peptide (SP).
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PMID:Possible coexistence of amino acid (gamma-aminobutyric acid), amine (dopamine) and peptide (substance P); neurons containing immunoreactivities for glutamic acid decarboxylase, tyrosine hydroxylase and substance P in the hamster main olfactory bulb. 245 79

We have studied the early development of subcortical projections to presumptive somatic sensory-motor areas of neocortex in the North American opossum Didelphis virginiana. The opossum is born in a very immature state, 12-13 days after conception, and climbs into an external pouch where it is available for experimental manipulation. Using the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, we have obtained evidence that axons from the dorsal raphe and superior central nuclei, the substantia nigra, the locus coeruleus and the parabrachial nuclei reach presumptive somatic sensory-motor areas of neocortex by at least postnatal day (PND) 10. Axons showing serotonin-like immunoreactivity, presumably from the dorsal raphe and/or superior central nuclei, and axons containing tyrosine hydroxylase immunoreactivity, presumably from the substantia nigra and/or locus coeruleus, are present in the same areas at birth or shortly thereafter. Thalamic axons do not grow into comparable areas of neocortex until after PND 10. Such axons reach the subplate region of ventrolateral neocortex first and then proceed dorsomedially; by estimated PD (EPND) 21, they are present in presumptive layers I, V and VI, but they do not innervate an identified layer IV until EPND 48. The developmental sequences suggested by our study are compared with those reported for other species and are discussed in light of their importance in the formation of major sensory and motor circuits.
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PMID:The early development of subcortical projections to presumptive somatic sensory-motor areas of neocortex in the North American opossum. 245 90

The results of many anatomical, physiological, and pharmacological studies suggest that substance P-containing neurons of the striatum project to the substantia nigra, and that substance P influences the activity of dopaminergic nigrostriatal neurons. The purpose of the present ultrastructural study was to employ dual immunocytochemical labeling to determine the morphological basis for the observed actions of substance P on nigral dopaminergic neurons. Substance P-like and tyrosine hydroxylase-like immunoreactivities were localized simultaneously at the ultrastructural level in the substantia nigra of the rat. A double label method was utilized which relied on a combination of the peroxidase-antiperoxidase method (Sternberger, 1979) for substance P, and immunogold or silver enhanced immunogold labeling for tyrosine hydroxylase. The present results indicate that tyrosine hydroxylase immunoreactive (THLI) dendrites in the substantia nigra receive synaptic input from terminals exhibiting substance P-like immunoreactivity. These findings support the idea that substance P is a major neurotransmitter in the striatonigral loop, and suggest that striatal substance P neurons act directly upon nigral dopaminergic cells.
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PMID:Direct demonstration of interactions between substance P immunoreactive terminals and tyrosine hydroxylase immunoreactive neurons in the substantia nigra of the rat: an ultrastructural study. 246 Sep 62

Following injections of small volumes (10-30 nl) of WGA-HRP (1-2%) into the ventral tegmental area, axonal transport of the lectin-peroxidase conjugate to ventral striatum was evaluated by light microscopy after TMB histochemistry and by electron microscopy following stabilization of the TMB reaction product with DAB and H2O2. Label was distributed more or less evenly in ventral striatum, with only slight patchiness observable in the boundary zone between the nucleus accumbens and ventromedial caudate-putamen. The electron microscope revealed that labeled axons contained markedly flattened vesicles and dense axoplasm and contacted perikarya, dendrites and dendritic spines of short (0.2-0.3 microns) symmetric appositions. Boutons with a similar triad of morphological features were observed in preparations processed for conventional electron microscopy and for tyrosine hydroxylase immunocytochemistry, suggesting that the characteristic morphological features observed are not an epiphenomenon related to histochemical processing.
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PMID:Evidence for a morphologically distinct subpopulation of striatipetal axons following injections of WGA-HRP into the ventral tegmental area in the rat. 246 96


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