INT78567

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Context Info
Confidence 0.68
First Reported 1998
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 25
Total Number 25
Disease Relevance 5.32
Pain Relevance 10.75

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (Th) mitochondrion (Th) oxidoreductase activity (Th)
nucleus (Th) cytoplasm (Th)
Anatomy Link Frequency
ventral 6
substantia nigra 4
striatum 2
brain 2
DRN 2
Th (Mus musculus)
Pain Link Frequency Relevance Heat
Substantia nigra 79 100.00 Very High Very High Very High
Ventral tegmentum 52 100.00 Very High Very High Very High
Catecholamine 45 100.00 Very High Very High Very High
Morphine 32 99.98 Very High Very High Very High
Locus ceruleus 43 99.68 Very High Very High Very High
cocaine 18 99.68 Very High Very High Very High
medulla 3 99.12 Very High Very High Very High
antinociception 4 98.88 Very High Very High Very High
Dopamine 769 98.72 Very High Very High Very High
midbrain 124 98.60 Very High Very High Very High
Disease Link Frequency Relevance Heat
Aging 33 98.84 Very High Very High Very High
Parkinson's Disease 202 97.48 Very High Very High Very High
Attention Deficit Hyperactivity Disorder 168 96.60 Very High Very High Very High
Injury 13 91.16 High High
Restless Legs Syndrome 63 91.12 High High
Targeted Disruption 79 90.56 High High
Schizophrenia 9 90.56 High High
Nociception 8 88.48 High High
Drug Dependence 13 86.72 High High
Toxicity 27 85.28 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Chronic opiate exposure induces numerous neurochemical adaptations in the noradrenergic system, including upregulation of the cAMP-signaling pathway and increased expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis.
Positive_regulation (increased) of Gene_expression (expression) of TH associated with catecholamine and opiate
1) Confidence 0.68 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12019333 Disease Relevance 0.09 Pain Relevance 0.60
Furthermore, in the previous study, subchronic antipsychotic medication reduced TH immunostaining in the striatum and caused shrinkage of dopaminergic cell bodies in substantia nigra.33 Lerner et al.34 reported changes of TH Vmax (maximal transport capacity) after chronic haloperidol administration and suggested that TH protein expression is elevated by long-term haloperidol treatment.
Positive_regulation (elevated) of Gene_expression (expression) of TH in substantia nigra associated with substantia nigra
2) Confidence 0.66 Published 2009 Journal Psychiatry Investigation Section Body Doc Link PMC2796069 Disease Relevance 0.73 Pain Relevance 0.33
These results suggest that chronic morphine upregulates TH expression via transcriptional mechanisms in the locus coeruleus but by post-transcriptional mechanisms in the ventral tegmental area.
Positive_regulation (upregulates) of Gene_expression (expression) of TH in locus coeruleus associated with ventral tegmentum, locus ceruleus and morphine
3) Confidence 0.60 Published 1998 Journal J. Neurosci. Section Abstract Doc Link 9822754 Disease Relevance 0.15 Pain Relevance 0.79
Increased expression of tyrosine hydroxylase mRNA was found in the ventral tegmental area and substantia nigra pars compacta of chronic caffeine-treated (20-80 mg/kg × 9 days) rats [23].
Positive_regulation (Increased) of Gene_expression (expression) of tyrosine hydroxylase mRNA in ventral associated with ventral tegmentum and substantia nigra
4) Confidence 0.57 Published 2010 Journal J Biomed Sci Section Body Doc Link PMC2843608 Disease Relevance 0.13 Pain Relevance 0.52
In this study, ser40 pTH activity, but not TH expression, was elevated in neglectful mice in ZI (Fig. 6).
Positive_regulation (elevated) of Gene_expression (expression) of TH
5) Confidence 0.51 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2276864 Disease Relevance 0 Pain Relevance 0.51
Chronic opiate exposure induces numerous neurochemical adaptations in the noradrenergic system, including upregulation of the cAMP-signaling pathway and increased expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis.
Positive_regulation (increased) of Gene_expression (expression) of tyrosine hydroxylase associated with catecholamine and opiate
6) Confidence 0.49 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12019333 Disease Relevance 0.09 Pain Relevance 0.60
Chronic opiate exposure induces numerous neurochemical adaptations in the noradrenergic system, including upregulation of the cAMP-signaling pathway and increased expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis.
Positive_regulation (upregulation) of Gene_expression (expression) of tyrosine hydroxylase associated with catecholamine and opiate
7) Confidence 0.49 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12019333 Disease Relevance 0.09 Pain Relevance 0.60
Chronic opiate exposure induces numerous neurochemical adaptations in the noradrenergic system, including upregulation of the cAMP-signaling pathway and increased expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis.
Positive_regulation (increased) of Gene_expression (expression) of TH associated with catecholamine and opiate
8) Confidence 0.49 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12019333 Disease Relevance 0.09 Pain Relevance 0.60
In LC, beta-gal expression was induced predominantly in tyrosine hydroxylase-expressing cells, whereas in the VTA and DRN the majority of cells expressing beta-gal were nonmonoaminergic.
Positive_regulation (induced) of Gene_expression (expressing) of tyrosine hydroxylase in DRN associated with ventral tegmentum and locus ceruleus
9) Confidence 0.49 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 11978842 Disease Relevance 0.20 Pain Relevance 1.27
Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only.
Positive_regulation (increases) of Gene_expression (levels) of TH in ventral associated with ventral tegmentum, locus ceruleus, cocaine and morphine
10) Confidence 0.46 Published 1998 Journal J. Neurosci. Section Abstract Doc Link 9822754 Disease Relevance 0.14 Pain Relevance 0.53
Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only.
Positive_regulation (increases) of Gene_expression (levels) of TH in ventral associated with ventral tegmentum, locus ceruleus, cocaine and morphine
11) Confidence 0.46 Published 1998 Journal J. Neurosci. Section Abstract Doc Link 9822754 Disease Relevance 0.13 Pain Relevance 0.52
Levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are known to be upregulated in specific brain regions by chronic administration of drugs of abuse.
Positive_regulation (upregulated) of Gene_expression (Levels) of tyrosine hydroxylase in brain associated with catecholamine
12) Confidence 0.46 Published 1998 Journal J. Neurosci. Section Abstract Doc Link 9822754 Disease Relevance 0.07 Pain Relevance 0.47
These and previous findings support the long-term efficacy of HCT1026 in preserving TH and DAT expression and function in striatum of ageing mice exposed to subchronic MPTP regimen.


Positive_regulation (preserving) of Gene_expression (expression) of TH in striatum associated with parkinson's disease and aging
13) Confidence 0.41 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC3000390 Disease Relevance 1.18 Pain Relevance 0.04
Together these findings strongly suggest that overexpression of a-Syn in TH-promoter mouse dopaminergic tissues reduced TH phosphorylation at TH-Ser(P)-19 and TH-Ser(P)-40, resulting in lower TH activity.
Positive_regulation (overexpression) of Gene_expression (overexpression) of TH-promoter
14) Confidence 0.33 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
We noted similar effects of transiently overexpressed a-Syn on TH-Ser(P)-19 in MN9D cells as well as in PC12 cells in which a-Syn overexpression is inducible (not shown), confirming an association between a-Syn and TH that reduces TH-Ser(P)-19 levels.
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of TH-Ser
15) Confidence 0.33 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
Furthermore, BV injection increased Fos expression in tyrosine hydroxylase immunoreactive neurons in the locus caeruleus, and this expression was unaltered by RTX pretreatment.
Positive_regulation (increased) of Gene_expression (expression) of tyrosine hydroxylase in neurons associated with locus ceruleus
16) Confidence 0.33 Published 2006 Journal J Pain Section Abstract Doc Link 16814689 Disease Relevance 0.50 Pain Relevance 0.70
Stereological cell counts of TH positive profiles in the substantia nigra and VTA were significantly elevated already at postnatal day two (data not presented), indicating an early expression of anatomical changes mediated by Pten ablation.
Positive_regulation (elevated) of Gene_expression (profiles) of TH in substantia nigra associated with ventral tegmentum and substantia nigra
17) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.22 Pain Relevance 0.43
Fostriecin produced a similar increase in Ser(P)-19 levels on TH, confirming the role of PP2A in TH-Ser(P)-19 dephosphorylation in MN9D cells (Fig. 2B; p < 0.05, one-way ANOVA).
Positive_regulation (increase) of Gene_expression (produced) of TH
18) Confidence 0.29 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
Evidence for regulation of TH by a-Syn in vivo was further corroborated by our data in mice lacking a-Syn, in which we saw effects opposite to those observed in a-Syn-overexpressing mice; namely, the ASKO mice had higher TH-Ser(P)-19 levels and significantly more active TH.
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of TH
19) Confidence 0.29 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.30 Pain Relevance 0.17
Evidence for regulation of TH by a-Syn in vivo was further corroborated by our data in mice lacking a-Syn, in which we saw effects opposite to those observed in a-Syn-overexpressing mice; namely, the ASKO mice had higher TH-Ser(P)-19 levels and significantly more active TH.
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of TH-Ser
20) Confidence 0.29 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.30 Pain Relevance 0.16

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