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)

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

We have employed immunocytochemical and axonal transport techniques to study the development of major projections to the dorsal striatum of the North American opossum. The opossum is born in a very immature state, 12-13 days after conception, and climbs into an external pouch where it remains attached to a nipple for several months. Its immaturity at birth and its protracted postnatal development make the opossum a good model for developmental studies. Although tyrosine hydroxylase-like immunoreactive (TH-LI), presumably dopaminergic, neurons were present in the ventral mesencephalon at birth (the presumptive substantia nigra and ventral tegmental area), there was no evidence for TH-LI axons in the striatal anlage. By postnatal day (PD)6, a few immunostained axons were found within the putamen. The subsequent growth of TH-LI axons into the striatum followed general caudal to rostral and ventrolateral to dorsomedial gradients and, at any age, they were most numerous in the areas exhibiting the greatest cytodifferentiation. By estimated (E)PD45, TH-LI axons were present in most, if not all, areas of the striatum. Serotoninergic (5-HT)-LI axons were found lateral to the presumptive striatum at birth but not within it. By PD7, however, a few 5-HT-LI axons could be identified in the putamen. The growth of 5-HT-LI axons into the striatum generally followed the same gradients described for TH-LI axons although at all ages their density was much less. Using the orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), evidence was obtained for the existence of thalamostriatal projections by PD5 and for corticostriatal projections by PD10. Crossed corticostriatal projections were present by EPD23. Our results suggest that the development of major projections to the striatum occurs postnatally in the opossum, rather than prenatally as in placental animals. The timetable for striatal innervation is discussed in light of the developmental sequences established for other motor circuits.
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PMID:The early development of major projections to the dorsal striatum in the North American opossum. 247 8

The afferent input to the basal forebrain cholinergic neurons from the pontomesencephalic tegmentum was examined by retrograde transport of wheatgerm agglutinin-horseradish peroxidase in combination with immunohistochemistry. Multiple tyrosine hydroxylase-, dopamine-beta-hydroxylase-, serotonin- and choline acetyltransferase-immunoreactive fibres were observed in the vicinity of the choline acetyltransferase-immunoreactive cell bodies within the globus pallidus, substantia innominata and magnocellular preoptic nucleus. Micro-injections of horseradish peroxidase-conjugated wheatgerm agglutinin into this area of cholinergic perikarya led to retrograde labelling of a large population of neurons within the pontomesencephalic tegmentum, which included cells in the ventral tegmental area, substantia nigra, retrorubral field, raphe nuclei, reticular formation, pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus, parabrachial nuclei and locus coeruleus nucleus. Of the total population of retrogradely labelled neurons, a significant (approximately 25%) proportion were tyrosine hydroxylase-immunoreactive and found in the ventral tegmental area (A10), the substantia nigra (A9), the retrorubral field (A8), the raphe nuclei (dorsalis, linearis and interfascicularis) and the locus coeruleus nucleus (A6), Another important contingent (approximately 10%) was represented by serotonin neurons of the dorsal raphe nucleus (B7), the central superior nucleus (B8) and ventral tegmentum (B9). A small proportion (less than 1%) was represented by cholinergic neurons of the pedunculopontine (Ch5) and laterodorsal (Ch6) tegmental nuclei. These results demonstrate that pontomesencephalic monoamine neurons project in large numbers up to the basal forebrain cholinergic neurons and may represent a major component of the ventral tegmental pathway that forms the extra-thalamic relay from the brainstem through the basal forebrain to the cerebral cortex.
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PMID:Afferents to the basal forebrain cholinergic cell area from pontomesencephalic--catecholamine, serotonin, and acetylcholine--neurons. 247 19

The source and possible role of excitatory amino acid projections to areas of the ventrolateral medulla (VLM) involved in cardiovascular control were studied. Following the injection of [3H]D-aspartate ([3H]D-Asp), a selective tracer for excitatory amino acid pathways, into vasopressor or vasodepressor areas of the VLM in rats, more than 90% of retrogradely labelled neurones were found in the nucleus of the solitary tract (NTS). Very few of the [3H]D-Asp-labelled cells were immunoreactive for tyrosine hydroxylase, none for phenylethanolamine-N-methyltransferase or gamma-aminobutyric acid. The density of labelled cells in the NTS was similar to that obtained with the non-selective tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and WGA-colloidal gold, but these tracers also labelled other cell groups in the medulla. Furthermore, the decrease in blood pressure, caused by pharmacological activation of neurones in the NTS of rats, or by electrical stimulation of the aortic depressor nerve in rabbits could be blocked by the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate injected into the caudal vasodepressor area of the VLM. This area corresponds to the termination of [3H]D-Asp transporting NTS neurones. These results provide evidence that a population of NTS neurones projecting to the VLM use excitatory amino acids as transmitters. Among other possible functions, this pathway may mediate tonic and reflex control of blood pressure via NMDA receptors in the VLM.
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PMID:Evidence for an excitatory amino acid pathway in the brainstem and for its involvement in cardiovascular control. 247 56

The light and electron microscopic localization of antigenic sites for a polyclonal antiserum directed against the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), was examined in the hippocampal formation of the rat brain with a double-bridged peroxidase-antiperoxidase method. By light microscopy, the majority of varicose processes with intense TH-like immunoreactivity (LI) were contained in the hilus of the dentate gyrus (DG) and strata radiatum and lacunosum-moleculare of the CA3 region of the hippocampus. Only a few immunoreactive fibers were observed in the molecular and granule cell layers of the DG, in strata oriens and pyramidale of CA3, and in all layers of CA1. Electron microscopy confirmed that these labeled processes were primarily axons and axon terminals. Terminals with TH-LI were 0.4-1.1 micron in diameter and contained many small clear vesicles and from 0 to 3 larger dense-core vesicles. The number and types of associations formed by terminals with TH-LI were remarkably similar in the DG and hippocampus proper despite known differences in intrinsic cells and function. In both regions, the majority of terminals with TH-LI formed junctions on small (distal dendrites (52% of 112 in the DG; 67% of 116 in CA3) and dendritic spines (30% in the DG; 18% in CA3) that were both asymmetric and symmetric. In the DG, axosomatic junctions (2% of 112) were symmetric and occurred exclusively on the perikarya of granule cells, whereas junctions on large (proximal) dendrites were more numerous (16%), exhibited symmetric as well as asymmetric membrane specializations, and were of both granule (molecular layer) and nongranule (hilus) cell origin. In CA3, synaptic contacts on perikarya (5% of 116) and large (proximal) dendrites (10%) of both pyramidal cell and nonpyramidal cell origin were few and all symmetric. The distribution and types of synaptic associations formed by terminals with TH-LI in the CA1 region paralleled that seen in the CA3 region. In both the dentate and hippocampus proper, 10% of the terminals with TH-LI were observed closely apposed to unlabeled terminals that formed asymmetric synapses with dendrites and dendritic spines. In rare instances, TH-immunoreactive terminals were found in close association with the basement membrane of blood vessels, astrocytic processes, or with other unlabeled terminals not forming recognizable junctions. In addition TH-LI was occasionally detected within the cytoplasm of a minority of astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ultrastructural localization of tyrosine hydroxylase-like immunoreactivity in the rat hippocampal formation. 256 53


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