Disease relevance of Th

• The terminals of preganglionic axons in the ciliary ganglion exhibited not only immunoreactivity for ChAT, but also for TH and contained stores of endogenous catecholamine [1].
• The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition [2].
• The present results suggest (1) that the postnatal increases in adrenal TH mRNA levels are not directly due to hypoxia at birth, and (2) that the increased mortality seen after hypoxia in nicotine pups concurs with a perturbed LC function in these animals [3].
• The preferential differentiation of T helper (Th) cells to Th1 or Th2 subsets is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases [4].
• Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores [5].

Psychiatry related information on Th

• Food deprivation decreased MAOA mRNA in the LC (but not RN), increased TH mRNA in the LC, and did not alter NET or 5HTT mRNA levels [6].
• Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology [7].
• Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and diethyldithiocarbamate, a dopamine beta hydroxylase inhbitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC [8].
• As shown previously, idiotype (Id) sharing between anti-2,4,6-trinitrophenyl T helper (Th) cells and antibodies in BALB/c mice results from immunoglobulin (Ig)-dependent selection of the T cell repertoire [9].
• With the dose used deprenyl recovers 50% DA levels and tyrosine hydroxylase activity depressed by the neurotoxin, normalizing locomotor activity of mice [10].

High impact information on Th

• Dopamine-deficient mice (Dbh(Th/+), Th-/-; hereafter DD mice) cannot synthesize dopamine in dopaminergic neurons [11].
• Peptide analogs that do not stimulate MBP-specific TH cells but bind to the I-Au molecule competitively inhibit T cell reactivity to MBP in vitro and prevent the induction of EAE in vivo [12].
• We have characterized TH cell reactivity in B10.PL and PL/J (H-2u) mice to 39 N-terminal MBP peptide derivatives of different lengths and with individual amino acid substitutions [12].
• Experimental autoimmune encephalomyelitis (EAE) results from T helper (TH) cell recognition of myelin basic protein (MBP) [12].
• Three different cases of pancreatic beta cell hyperplasia in mice are accompanied by an increase in a subclass of cells expressing tyrosine hydroxylase (TH), a neuronal enzyme [13].

Chemical compound and disease context of Th

• Rats sympathectomized as neonates by treatment with 6-hydroxydopamine subsequently had a greater proportion of neurons possessing detectable TH-IR in the ciliary ganglion; both the TH-IR perikarya and their axons in the iris were more intensely immunofluorescent [1].
• Differential expression of monoamine oxidase A, serotonin transporter, tyrosine hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food deprivation [6].
• Concomitant elevation of tyrosine hydroxylase and dopamine beta-hydroxylase by cyclic AMP in cultured mouse neuroblastoma cells [14].
• Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity [15].
• Tyrosine hydroxylase, dopa oxidase, and peroxidase activities were studied in soluble fractions of B16 melanoma tumor homogenates by polyacrylamide gel disc electrophoresis [16].

Biological context of Th

• A DNA mapping panel derived from an interspecific backcross was used to position the mouse insulin-2 locus (Ins-2) on Chromosome 7, near H19 (0/114 recombinants) and Th (1/114 recombinants) [17].
• Mutant ganglionic anlagen also fail to switch on the genes that encode two enzymes needed for the biosynthesis of the neurotransmitter noradrenaline, dopamine-beta-hydroxylase and tyrosine hydroxylase, demonstrating that Phox2b regulates the noradrenergic phenotype in vertebrates [18].
• This disappearance is caused by apoptosis revealed by the presence of activated caspase 3 in the dying tyrosine hydroxylase-positive mutant cells [19].
• The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development [20].
• Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH) [20].

Anatomical context of Th

• Development of the dopaminergic phenotype in the mouse substantia nigra (SN) was studied by monitoring tyrosine hydroxylase (TH), the rate-limiting enzyme in CA biosynthesis in vivo and in culture [21].
• Increased tyrosine hydroxylase is also observed in the BDNF+/- carotid artery, another sympathetic neuron target [22].
• In the substantia nigra and ventral tegmental area where TH-IN are normally present, no differences either in the immunostaining of TH-IN or the pattern of TH immunoreactive fibers were detected between MObr/y and controls [23].
• We have measured the effects of l-DOPA on cell viability, tyrosine hydroxylase (TH) expression, DA metabolism and glutathione levels of parkin knockout (PK-KO) midbrain cultures [24].
• Effects of systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine beta-hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus [25].

Associations of Th with chemical compounds

• The molecular interaction between the Y(1) receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y(1) receptor-expressing SK-N-MC cells transfected with a TH promoter sequence [26].
• Immunoblot analysis revealed that SK elicited a parallel increase in TH enzyme protein [21].
• Although diminished in magnitude, a sweat response to pilocarpine was also noted in TH -/- mice at P21 [27].
• Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability [28].
• Finally, phospho-Ser31 TH levels were increased in dopaminergic neurons of rats trained to chronically self-administer cocaine [29].

Physical interactions of Th

• Although the function of alpha-synuclein is not thoroughly elucidated, we found that alpha-synuclein regulates dopamine synthesis by binding to and inhibiting tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis [30].
• The extent of the lesion was measured by striatal DA transporter binding and stereological estimation of the number of tyrosine hydroxylase immunoreactive neurones in the substantia nigra pars compacta (SNc) [31].
• The hyperdopaminergic state of GABAB1-/- mice is accompanied by molecular changes, including reduced levels of tyrosine hydroxylase mRNA, D1 receptor binding-sites and Ser40 phosphorylation of tyrosine hydroxylase [32].
• In addition to the classic major histocompatibility complex-restricted Th cell, the response was also dependent upon the so-called second order Th2 population, which binds to idiotypic determinants, is carrier specific, but does not require hapten linked to carrier for function [33].

Enzymatic interactions of Th

• Here we report that Cdk5 phosphorylates tyrosine hydroxylase (TH), the key enzyme for synthesis of dopamine [29].
• Enhanced expression of Ca2+ channel alpha1A and beta4 subunits and phosphorylated tyrosine hydroxylase in the adrenal gland of N-type Ca2+ channel alpha1B subunit-deficient mice with a CBA/JN genetic background [34].
• Immunohistochemical staining with a TH monoclonal antibody coupled with confocal microscopy was employed on vibratome-cut brain sections of female GnRH-green fluorescent protein (GFP) transgenic mice to evaluate possible appositions between GnRH and tuberoinfundibular dopaminergic (TIDA) neurons [35].

Co-localisations of Th

• BDNF has been colocalized by immunocytochemistry with tyrosine hydroxylase (TH) in nerve fibers and nerve terminals within the lateral septum of rats [36].

Regulatory relationships of Th

• However, tyrosine administration did not enhance phosphorylated TH levels or enzyme catalytic activity in raclopride-stimulated NSDA neurons in alpha-synuclein knockout mice [37].
• Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site [38].
• Expanded ES NP-derived TH(+) neurons coexpressed additional DA markers such as dopa decarboxylase and DAT (dopamine transporter) [39].
• Brains of female and male homozygous PRL-null (- or -) mice and normal heterozygous (+ or -) siblings were compared using formaldehyde-induced endogenous catecholamine fluorescence and tyrosine hydroxylase (TH) immunocytochemistry [40].
• Moreover, pretreatment with WIN-51,708 also prevented the reduction of TH levels induced by METH as well as the induction of GFAP in astrocytes [41].

Other interactions of Th

• Wnt-3a promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 (Nurr1) but did not increase the number of tyrosine hydroxylase-positive neurons [42].
• The present study was designed to test whether PRL replacement during the early postnatal period would increase DA and TH expression in dwarfs [43].
• The present study supports the hypothesis that alpha-synuclein functions as a molecular chaperone protein that regulates the phosphorylation state of TH in a substrate and activity-dependent manner [37].
• TH appears in these neurons at E11.5, consistent with a putative role of Pitx3 in TH transcription [38].
• Involvement of leukemia inhibitory factor in the increases in galanin and vasoactive intestinal peptide mRNA and the decreases in neuropeptide Y and tyrosine hydroxylase mRNA in sympathetic neurons after axotomy [44].

Analytical, diagnostic and therapeutic context of Th

• Brains were evaluated by catecholamine histofluorescence and TH immunocytochemistry at the end of the treatment period [43].
• All animals were killed 14 weeks after transplantation, after which the graft-bearing organs were processed for indirect immunofluorescence for neuropeptides and tyrosine hydroxylase (TH), and with acetyl cholinesterase (AchE) staining to visualize nerve fibers [45].
• In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy [2].
• 3. Chemical sympathectomy abolished TH- and NPY-IR nerve structures in cavernous smooth muscle bundles [46].
• Two weeks after transplantation, surviving TH(+) cells were present [47].

References