Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC12 pheochromocytoma cells was initially depressed reaching a nadir at 6 hours post-inoculation, but recovered rapidly with a return to baseline activity by 8 to 9 hours post-inoculation. Subsequently, TH activity again fell with a second more variable rise in activity occurring at 24 hours post-inoculation. Studies with metabolic inhibitors and 2 temperature-sensitive viral mutants indicated that these alterations of TH activity were dissociated from morphological cytopathology and likely required expression of "late" viral gene products. Immunotitration using anti-TH antibody suggested that early depression of TH activity resulted principally from loss of enzyme protein rather than simple enzyme inactivation, and that reconstitution of activity at 9 hours was related to augmented enzyme synthesis. These observations illustrate the complexity of perturbed cellular metabolism during HSV-1 infection and suggest involvement of two unexpected processes: alteration of a specialized cell function as a result of viral genes expressed late in the replicative cycle, and augmented synthesis of a cell-coded gene product during the course of infection.
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PMID:Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1. 285 60

The role of spinal pathways in the regulation of adrenal medullary tyrosine hydroxylase and catecholamines was studied in adult rats subjected to spinal cord transection at the third thoracic level. In these animals the sympathoadrenal preganglionic neurons were isolated from their supraspinal afferents. This treatment led after three days to a progressive reduction of tyrosine hydroxylase activity and dopamine content (as compared to unoperated controls) until at least the 10th day. The results of the administration of dexamethasone or adrenocorticotropic hormone to spinalized rats suggest that in these animals glucocorticoid hypersecretion is not involved in the decline of adrenal tyrosine hydroxylase and that in fact adrenocorticotropic hormone supplementation can prevent it. A neurogenic origin for the depression of adrenomedullary function is favoured because unilateral splanchnicotomy (which by itself does not affect adrenal tyrosine hydroxylase), prior to cord section, prevented the diminution of tyrosine hydroxylase activity in the denervated gland. The decline of adrenal tyrosine hydroxylase and dopamine after spinal section may result from a decrease of modulatory impulses to the adrenal from decentralized sympathoadrenal preganglionic neurons in the isolated cord, following the loss of a descending facilitation of these neurons and/or the release of a segmental interneuronal inhibition of these neurons from a descending inhibitory influence. Such descending pathways may decussate partially below the low cervical level because rats with hemisection of the cord at C6-C7 exhibited no decline of adrenal tyrosine hydroxylase or of dopamine measured on either side seven days postoperatively.
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PMID:Differential effects of transection of the spinal cord and splanchnic nerve on adrenal tyrosine hydroxylase and catecholamines. 285 54

The results reported here indicate that treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused significant changes in the dopamine-synthesizing enzyme, tyrosine hydroxylase. The authors examined the effects of two doses of MPTP on the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in the striatum, and also the time-course of these effects. Rats received an intraperitoneal loading dose, followed by a 24-hr infusion of MPTP (total doses of 21 or 42 mg) from subcutaneously-implanted osmotic pumps. Seven days after treatment, the activity of tyrosine hydroxylase was decreased by MPTP (42 mg); however, the activity of tryptophan hydroxylase was not affected. In time-course experiments, the activity of tyrosine hydroxylase was maximally reduced at 3 and 7 days after treatment with MPTP (42 mg). The activity of tryptophan hydroxylase did not significantly change at any time-point. Concurrent administration of haloperidol (HALO; 2 mg/kg, 4 doses) with MPTP significantly enhanced the depression of the activity of tyrosine hydroxylase in the striatum caused by MPTP, while treatment with haloperidol alone had no such effect. Concentrations of dopamine in the striatum were maximally decreased to approx. 50% of control in animals treated with haloperidol and MPTP (42 mg), whereas treatment with MPTP alone decreased concentrations of dopamine to approx. 70% of control.
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PMID:Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase and tryptophan hydroxylase in rat. 287 13

The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
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PMID:The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. 287 93

Manic depression is a severe cyclic mental illness that can be unipolar or bipolar and has a lifetime risk of approximately 7 per 1,000 in most populations. Families with multiple cases of manic depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission. Psychoactive antidepressant and stimulant drugs that help to ameliorate depression and mania are thought to act by affecting catecholamine neurotransmitter systems such as adrenaline, noradrenaline and dopamine, amongst others. Mutations affecting the tyrosine hydroxylase (TH) gene, which encodes the rate-limiting enzyme for the synthesis of these three neurotransmitters, might therefore be responsible for causing the manic depressive phenotype. We have studied three Icelandic kindreds amongst whom it appears that a single autosomal dominant disease allele is segregating. In these families there were 44 cases amongst 73 individuals at risk. Genetic linkage studies were carried out using clones encoding tyrosine hydroxylase the variable portion of the Harvey-ras-1 (HRAS1) locus and the variable region of the insulin gene (INS). All three markers are closely linked on chromosome 11 and were used to observe the segregation of restriction fragment length polymorphisms (RFLPs) in the three affected kindreds. We found no evidence for linkage to these markers in any of the three families. In contrast, Gerhard et al. found linkage between manic depression and HRAS1 in a single large Amish kindred. We conclude that there is genetic heterogeneity of linkage in manic depression. Therefore mutations at different loci are responsible for the manic depressive phenotype in the Amish and in Iceland.
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PMID:Molecular genetic evidence for heterogeneity in manic depression. 288 Dec 10

As determined by autoradiographic techniques, multiple high doses of methamphetamine elicited a reduction in dopamine receptor population (both D1 and D2) in several areas of the rat central nervous system. D1 receptors were labeled with the D1-selective antagonist, [3H]SCH 23390, and D2 receptors were labeled with the D2-selective neuroleptic, [3H]sulpiride. Scatchard analysis, obtained from saturation data in caudate-putamen, indicated that the receptor alterations were due to a decrease in the number of receptors (Bmax) without an apparent change in affinity (Kd). A time course demonstrated that five doses of methamphetamine were required to elicit significant changes in receptors in most brain areas examined. The onset of the receptor alterations in various brain regions correlated with the development of methamphetamine-induced depression of striatal tyrosine hydroxylase activity. In most brain areas, the dopamine receptors returned to normal within 7 days following methamphetamine.
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PMID:Methamphetamine-induced reduction in D1 and D2 dopamine receptors as evidenced by autoradiography: comparison with tyrosine hydroxylase activity. 289 Oct 82

The role of the serotonin uptake carrier in the methamphetamine-induced depression of serotonin synthesis was examined. In vivo, coadministration of citalopram or chlorimipramine with methamphetamine blocked the irreversible depression of tryptophan hydroxylase activity observed in the neostriatum and cerebral cortex after repeated administration of high doses of methamphetamine. The methamphetamine-induced reduction of neostriatal serotonin and 5-hydroxyindoleacetic acid was also attenuated by the two uptake inhibitors. In contrast, neither drug antagonized the depression of neostriatal tyrosine hydroxylase activity observed after methamphetamine administration. Citalopram also blocked the reversible inhibition of tryptophan hydroxylase activity observed after the acute administration of methamphetamine. In vitro, citalopram significantly inhibited methamphetamine-induced [3H]serotonin release from neostriatal slices. The results demonstrate that inhibitors of the serotonin uptake carrier can antagonize both the in vivo and in vitro effects of methamphetamine on serotonergic neurons. Furthermore, the methamphetamine-induced depression of serotonin synthesis is dependent upon a functional serotonin uptake system.
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PMID:Role of the serotonin uptake carrier in the neurochemical response to methamphetamine: effects of citalopram and chlorimipramine. 385 54

Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.
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PMID:Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. 610 22

Tyrosine hydroxylase (TH) levels in the rat neostriatum are decreased by chronic treatment with methamphetamine. GABAergic neurons could potentially interact with the nigrostriatal dopaminergic neurons in either the neostriatum or the substantia nigra; therefore, the GABA transaminase inhibitors, amino-oxyacetic acid, gamma-acetylenic GABA and ethanolamine-O-sulfate, were evaluated for possible influences on the methamphetamine-induced decrease in TH. TH was measured by the procedure of Nagatsu et al. (1964). Methamphetamine (10 mg/kg, s.c.) was given every 6 h for 24 h. Thirty-six h after initiation of the methamphetamine treatment, neostriatal TH activity was approximately 70% of control. Concurrent administration of amino-oxyacetic acid (20 mg/kg, i.p.) or gamma-acetylenic GABA (15 mg/kg, i.p.) with methamphetamine completely blocked the TH depression. Dose-response curves were constructed for amino-oxyacetic acid and gamma-acetylenic GABA. A single intraventricular injection of ethanolamine-O-sulfate (400 micrograms/rat), 2-6 h before initiating the methamphetamine regimen, also completely blocked the TH depression. These data suggest that the striatonigral or other GABAergic systems are involved in the regulation of the functional state of the nigrostriatal dopaminergic neurons, and that enhanced GABAergic function will antagonize the effects of high doses of methamphetamine.
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PMID:Blockade of methamphetamine-induced depression of tyrosine hydroxylase by GABA transaminase inhibitors. 610 24

Acute administration of methamphetamine produced a dose-dependent depression of tryptophan hydroxylase (TPH) activity. The depression was observed in several serotonergic nerve terminal regions of the rat brain and spinal cord. Complete recovery of TPH activity following methamphetamine treatment occurred in all regions, but the time to recovery varied with the dose administered. In contrast to TPH, tyrosine hydroxylase (TH) was not affected by a single injection of methamphetamine. The data are discussed in the context of the effects of single versus repeated doses of methamphetamine on tryptophan and tyrosine hydroxylase.
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PMID:Methamphetamine-induced depression of tryptophan hydroxylase: recovery following acute treatment. 612 Aug 43


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