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)

Human fetal hippocampal tissue from normal women was obtained following elective abortion in the 8th to the 11th week of gestation. The hippocampal tissue was transplanted to the anterior chamber of the eye of adult athymic nude rats, where it was allowed to develop for up to 9 months before histological and electrophysiological evaluation. The transplants were revascularized from the host iris and many grew extensively in oculo. Large neurons were present in all transplants. Immunohistochemical studies revealed glutamic acid decarboxylase-containing terminals and clusters of gamma-aminobutyric acid-positive nerve cell bodies within the transplants, as well as scattered tyrosine hydroxylase-positive and acetylcholinesterase-containing fibers. Single neurons recorded extracellularly from transplants 4-9 months in oculo showed a slow spontaneous discharge, with both complex and single action potentials. Stimulation of the transplant surface evoked a small initial wave followed by a larger and longer-lasting field potential, similar to that seen in hippocampus in situ. A conditioning-testing paradigm was used to evaluate the presence of inhibitory circuitry in the hippocampal transplants. Significant suppression of the evoked test response was seen with interstimulus intervals ranging from 20 to 500 ms. Superfusion of enkephalin (100-300 nM) or penicillin (1600 U/ml) increased slow-wave activity, as did tetanic electrical stimulation. These treatments appeared to generate ictal-like activity, which in some cases persisted as interictal spikes. Illumination of the retina also increased neuronal activity, presumably by reflex activation of cholinergic afferents from the parasympathetic innervation of the iris. Taken together, our data suggest that fragments of hippocampus from aborted first trimester human fetuses, grafted to the eye chamber of rodent hosts, develop many organotypic histological and physiological features. This preparation may provide a unique means for the study of neurobiological properties of human brain in both normal and disease states.
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PMID:Morphological and electrophysiological studies of human hippocampal transplants in the anterior eye chamber of athymic nude rats. 270 63

A pre-embedding immunostaining procedure was developed using ferritin and peroxidase to enable simultaneous electron microscopic localization of two antigens in the same tissue section. This method was used to study the anatomic relationship between glutamic acid decarboxylase (GAD) immunoreactive axons and tyrosine hydroxylase (TH) - containing neurons of the rat arcuate nucleus. The findings provide ultrastructural evidence that GAD-immunoreactive terminals establish symmetric (Gray II) synapses on TH-reactive neurons.
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PMID:Application of avidin-ferritin and peroxidase as contrasting electron-dense markers for simultaneous electron microscopic immunocytochemical labelling of glutamic acid decarboxylase and tyrosine hydroxylase in the rat arcuate nucleus. 286 85

In the mouse, monosodium glutamate (MSG) administered neonatally provokes the necrosis of most dopaminergic perikarya in the arcuate nucleus, as classically described, but also stimulates surviving neurons as shown by their increase in both size and immunoreactivity for tyrosine hydroxylase (TH). In the treated animals, TH-immunoreactive axons rarefy in the median eminence (ME) external zone, but postnatal dopaminergic innervation of the intermediate lobe (IL) normally develops and even, due to enlarged axonal varicosities, is more conspicuous than in the control littermate IL at same stages. gamma-Aminobutyric acid-ergic (GABAergic) projections in the ME and the IL, revealed with a glutamic acid decarboxylase antiserum, have the same distribution as TH-immunoreactive axons and present the same modifications in the MSG-treated animals. No clearcut differences in dopaminergic and GABAergic innervation patterns can be observed in the IL in treated and control adult mice.
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PMID:Opposite effects of monosodium glutamate on the dopaminergic and GABAergic innervations of the median eminence and the intermediate lobe in the mouse. 286 9

We found that the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) (EC 1.14.16.2), dopamine beta-hydroxylase (EC 1.14.17.1), and phenylethanolamine N-methyltransferase (EC 2.1.1.28) share similar protein domains in their primary structures and that they share common gene coding sequences. In a recent report we also demonstrated that antiserums directed against choline acetyltransferase (EC 2.3.1.6), glutamic acid decarboxylase (EC 4.1.1.15), and TH cause specific complement-mediated lysis of cholinergic, gamma-aminobutyric acid-ergic, and dopaminergic subpopulations of synaptosomes, respectively. This interaction of specific antibodies to the specific subpopulation of synaptosomal membrane, e.g., recognition of antibody to TH to only the dopaminergic subpopulation of synaptosomal membrane protein, indicates that the neurotransmitter enzyme and membrane protein of its own synaptosomes may also share common protein domains. Therefore, we postulate that the specific neurotransmitter biosynthetic enzyme and a certain membrane protein of the nerve endings may share similar gene coding sequences, and that expression of these proteins may determine the phenotype of the neuron.
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PMID:Genes for neurotransmitter synthesis, storage, and uptake. 286 77

A microinjection of a homogenate of scrapie agent-infected brain (strain 263 K) into the nigrostriatal system in the golden hamster is followed by the progressive development of the disease which terminates by the death of animals around the 4th month postinoculation. These intracerebral inoculations induce more rapid changes in neuronal activity which can be revealed by the assessment of the specific synthesizing enzymes of neurotransmitter systems. The microinoculation of a homogenate of an infected brain unilaterally into the substantia nigra (SN) provokes a decrease in tyrosine hydroxylase (TH), the synthesizing enzyme for dopamine in the dopaminergic neurones, in the striatum ipsilateral to the injected SN. This biochemical response, specifically induced by the active pathogen, is detectable as soon as the 5th day postinoculation and is detectable towards the 80th day. A return of TH levels to control values is detected after this period. At the end of the incubation period and towards the death of the animals, TH is not different from control TH measured from intact animals. The decrease in TH is concomitant with an increase in striatal glutamic acid decarboxylase (GAD), the synthesizing enzyme for gamma-aminobutyric acid (GABA), measured 20 days postinoculation with no change in choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. Studies of the biochemical responses associated locally to the scrapie agent inoculation have been performed at the striatal level. The intrastriatal administration of the infective agent induces 20 days postinoculation an increase in GAD with no change in TH and ChAT. Ninety days postinoculation, a decrease in GAD was detected associated with an increase in TH with no change in ChAT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in tyrosine hydroxylase, glutamic acid decarboxylase and choline acetyltransferase after local microinoculation of scrapie agent into the nigrostriatal system of the golden hamster. 286 98

Male Wistar rats were fed a diet of 24% protein either ad lib (AL) or every other day (EOD) beginning shortly after weaning. Rats were killed at 6 or 24-months of age. The corpus striatum, cerebral cortex, hippocampus, and cerebellum were assayed for muscarinic cholinergic receptor binding and the activities of choline acetyltransferase (ChAT), L-glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH). Sensecent rats maintained on EOD feeding schedules from weaning showed a markedly higher density of striatal muscarinic binding sites and higher activities of cerebellar, hippocampal, and striatal ChAT, as compared with values in AL-fed rats. Regional GAD and TH activities were relatively unaffected by EOD feeding; however, at 6 months, EOD-fed rats had higher cortical GAD and lower cortical TH activities than corresponding AL-fed rats. EOD feeding for only 2 weeks produced no significant effects on neurochemical parameters examined in 24-month-old rats. We conclude that EOD feeding from weaning can alter neurochemical markers of senescence in rat brain; that cholinergic systems are affected in particular; and that the observed alterations produced by EOD feeding represent chronic rather than acute effects.
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PMID:Effects of intermittent feeding on neurochemical markers in aging rat brain. 286 86

We surveyed retinas of Raja erinacea, Mustelus canis, and Squalus acanthias for neurotransmitter substances by using antisera directed against the substances themselves or against their synthesizing enzymes. Both the peroxidase-antiperoxidase (PAP) and indirect fluorescent techniques were employed to visualize the primary antisera. In all three species positive results were obtained with antisera directed against tyrosine hydroxylase (TOH), glutamic acid decarboxylase (GAD), serotonin (5-HT), and leucine enkephalin (Lenk). Antisera directed against glucagon, neurotensin, beta-endorphin, vasoactive intestinal peptide, or bombesin failed to show any specific staining. Immunoreactivity was located in amacrine, interplexiform, and horizontal cells as well as in axons of the optic fiber layer. The four antisera labelled different amacrine cell classes, distinguished on the bases of perikaryal morphology and the distribution of cell processes in the inner plexiform layer (IPL). Amacrine cells that labelled with the same marker were seen to have different morphologies in the species studied. Thus, TOH-like immunoreactivity was distributed in layers 1, 3, and 5 of the IPL in Mustelus but only in layers 1 and 3 in Raja retina. GAD-like immunoreactivity was found diffusely over all layers of the IPL in Raja, but in Mustelus it was confined primarily to layers 1, 3, and 5 of the IPL. Lenk- and 5-HT-like immunoreactivities showed similar species variations. Two neurochemical classes of interplexiform cell were identified in this study. In Mustelus GAD-like and Lenk-like immunoreactive interplexiform cells were seen whereas in Raja only GAD-positive interplexiform cells were detected. In squalus no unequivocal demonstration of any interplexiform cell was made with these antisera. The GAD antiserum also labelled a subset of the horizontal cells in the dorsal retina of Raja. TOH and 5-HT-antisera labelled axons in the optic fiber layer of all three species but reactive ganglion cell perikarya were not identified.
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PMID:Retinal neurochemistry of three elasmobranch species: an immunohistochemical approach. 286 65

Studies of various parameters of amino acid and catecholamine metabolism in human cerebral cortex have provided a number of biochemical markers that appear to delineate areas of focal epileptic activity. These observations have been consolidated further by investigations of a number of experimental models of epilepsy in animals. In appraising this data, it is important to take into consideration whether the tissue samples were obtained during an actual seizure state or in an interictal period. It is also important when possible to assess the extent of astrogliosis and neuronal loss. Sites of spontaneously active epileptic spiking in the cerebral neocortex have a somewhat different amino acid profile when compared to gray matter obtained from surrounding nonspiking gyri several centimeters away. There is an elevation in glycine content, a relative diminution in taurine, and a trend towards lowered glutamic acid levels. However, the concentrations of the eight amino acids measured appear in both the foci and surround to still be within the general range for normal tissue. Measurements of key enzymes involved in the synthesis and regulation of neurotransmitters provide a complementary method of evaluating functional changes in epileptic brain as they are generally less labile than their substrates. There is a moderate increase in the activity of glutamic acid dehydrogenase, an enzyme that plays an important role in the synthesis of glutamic acid from glucose. In some patients a decrease in glutamic acid decarboxylase has also been reported: this enzyme forms gamma-aminobutyric acid (GABA) from glutamic acid and is thus important for inhibition in the central nervous system. Moreover, there is a striking increase in the activity of tyrosine hydroxylase, the rate-limiting enzyme responsible for catecholamine synthesis. The possibility of a focal abnormality in catecholamine metabolism is reinforced by the simultaneous finding of a relative decrease in the number of alpha-1 postsynaptic receptor sites. An important marker of energy metabolism in neural tissue, Na+,K+-ATPase activity, has also been found to be decreased in actively spiking human cerebral cortex. Data from experimental animal foci produced by topical application of convulsant agents show a consistent drop in glutamic acid tissue content. This can be matched to an efflux of glutamic acid from the cortical surface, which in turn is proportional to the electrographic activity of the spike focus. In addition, there is often also a decrease in taurine and GABA in such foci, as well as an increase in the levels of a number of neutral amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Amino acid and catecholamine markers of metabolic abnormalities in human focal epilepsy. 287 18

This study examines the effect of chronic administration of misonidazole on four neurotransmitter pathways (norepinephrine, dopamine, acetylcholine, and GABA) of the central nervous system (CNS). Biochemical assays examined the neurotransmitter synthesizing enzymes tyrosine hydroxylase (TOH) for catecholamines and choline acetyltransferase (CAT) for acetylcholine. An immunocytochemical stain for glutamic acid decarboxylase (GAD) was used as an enzymatic marker for GABAergic neurons. In drug-treated mice, enzymatic activity for TOH as well as the total concentration of enzyme was significantly increased in the locus coeruleus (LC), a principal norepinephrine-containing nucleus of the brainstem, but not in other brain regions. Correlative histofluorescence examination of the LC also showed an increase in the fluorescence intensity of noradrenergic neurons of the nucleus. In contrast, CAT activity was not different from controls in any of the areas examined. In the brainstem, immunocytochemical staining for GAD showed a significant reduction in the number of immunoreactive varicosities juxtaposed to neurons of the lateral vestibular nucleus suggestive of a loss of afferent GABAergic input from the cerebellum. These data suggest that both norepinephrine and GABAergic systems may be altered in selective nuclei of the CNS by chronic administration of misonidazole, and that drug related changes in NE and GABA may underline some of the neurotoxic side effects of MISO and/or exacerbate a patient's pre-existing cardiovascular or neurological problems.
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PMID:Effect of misonidazole on neurotransmitter systems. 287 48

Immunogold staining (IGS) for glutamic acid decarboxylase (GAD) was combined with the peroxidase-antiperoxidase (PAP) technique for tyrosine hydroxylase (TH) to analyze gamma-aminobutyric acid-catecholaminergic neuronal interactions in the rhesus hypothalamus. At the light-microscopic level, TH-immunoreactive (-IR) perikarya and their fibers (brown) were observed in the anterior ventral periventricular area (AVPV), the arcuate nucleus (ARC) and the adjacent periventricular zone (ARC-PVZ). GAD-IR processes (light red) were also present throughout the hypothalamus and appeared to contact some TH-IR neurons. At the electron-microscopic level, PAP was present in perikarya, dendrites, axons and axon terminals of TH-IR neurons. Colloidal gold particles (15 nm) were found only in dendrites and axon terminals of GAD-IR neurons. Labeled GAD terminals typically contained small, clear synaptic vesicles, while TH terminals contained these and sometimes one or two dense-core vesicles. In the ARC and ARC-PVZ, asymmetrical (Gray I) axodendritic synapses occurred between GAD and TH-IR profiles, with TH/GAD directionality more prevalent. Symmetrical (Gray II) synapses were less common, with either TH or GAD presynaptic in axodendritic and dendrodendritic contacts. GAD/GAD interactions were not observed, but TH/TH contacts appeared to be mostly dendrodendritic. In the AVPV, only symmetrical synapses were encountered, and their directionality was difficult to determine. GAD- and TH-IR dendrites frequently established dendrodendritic synapses, but GAD/TH dendrosomatic synapses were seldom seen. These results illustrate the complex interactions of GAD- and TH-containing elements in the neuroendocrine hypothalamus.
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PMID:GABAergic and catecholaminergic synaptic interactions in the macaque hypothalamus: double label immunostaining with peroxidase-antiperoxidase and colloidal gold. 287 51


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