INT107103

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Context Info
Confidence 0.59
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 21
Total Number 21
Disease Relevance 10.38
Pain Relevance 5.28

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

cell differentiation (Ntrk2) cytosol (Ntrk2) plasma membrane (Ntrk2)
kinase activity (Ntrk2)
Anatomy Link Frequency
neurons 4
soma 2
dorsal horn 2
dendrites 1
forebrain 1
Ntrk2 (Mus musculus)
Pain Link Frequency Relevance Heat
dorsal root ganglion 110 99.96 Very High Very High Very High
Pain 78 99.38 Very High Very High Very High
intrathecal 12 99.36 Very High Very High Very High
Dorsal horn 18 99.16 Very High Very High Very High
antidepressant 207 98.72 Very High Very High Very High
nociceptor 142 98.70 Very High Very High Very High
trigeminal ganglion 303 96.52 Very High Very High Very High
Sciatic nerve 2 95.36 Very High Very High Very High
Thermal hyperalgesia 11 94.48 High High
Hippocampus 141 93.92 High High
Disease Link Frequency Relevance Heat
Repression 40 100.00 Very High Very High Very High
Ganglion Cysts 492 99.96 Very High Very High Very High
Targeted Disruption 289 99.88 Very High Very High Very High
Pain 91 99.38 Very High Very High Very High
Disease 31 98.28 Very High Very High Very High
Suicidal Behaviour 369 97.96 Very High Very High Very High
Nociception 91 95.32 Very High Very High Very High
Hyperalgesia 21 94.48 High High
Cognitive Disorder 16 93.24 High High
Brain Injury 5 90.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
However, in the animal models of pain tested in this study, genetic depletion of trkB.T1 results in attenuation of pain.
Negative_regulation (depletion) of trkB associated with pain
1) Confidence 0.59 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.53 Pain Relevance 0.34
If trkB.T1 is up-regulated in the dorsal horn following noxious stimulation, then genetic depletion of trkB.T1 [23] would be expected to mitigate nocifensive behaviors in these models.
Negative_regulation (depletion) of trkB in dorsal horn associated with dorsal horn
2) Confidence 0.59 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.49 Pain Relevance 0.32
Loss of Runx3 may lead to the failure of TrkB and TrkC to segregate into distinct lineages, consistent with previous work demonstrating that Runx3 represses TrkB expression while promoting expression of TrkC [23,44].
Negative_regulation (failure) of TrkB
3) Confidence 0.55 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.27 Pain Relevance 0.16
The number of TG neurons was strongly decreased in the knockout mice as compared to wildtype and heterozygous mice (82%, 39%, and 48% reduction for trkA, trkB and trkC, respectively).
Negative_regulation (reduction) of trkB in neurons associated with targeted disruption
4) Confidence 0.54 Published 2004 Journal Acta Histochem. Section Abstract Doc Link 15530548 Disease Relevance 0.52 Pain Relevance 0.29
One of the functions of Runx3 is to repress TrkB when DRG neurons acquire TrkC+ identity (Figure 1a) [25].
Negative_regulation (repress) of TrkB in neurons associated with dorsal root ganglion
5) Confidence 0.51 Published 2008 Journal Neural Develop Section Body Doc Link PMC2531103 Disease Relevance 1.24 Pain Relevance 0.46
The prevailing view has been that trkB.T1 expression leads to dominant negative inhibition of full-length trkB signaling and a reduction in the activation of downstream signaling molecules [17-23,33].
Negative_regulation (inhibition) of trkB
6) Confidence 0.43 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.68 Pain Relevance 0.36
In saline group, 7,8-DHF and deoxygedunin substantially reduced the immobility time; in contrast, 7,8-DHF and deoxygedunin had no significant effect in mice, when TrkB was blocked by 1NMPP1 (Figure 6B), suggesting that inhibition of the TrkB signaling cascade inhibits the antidepressant effect of these drugs.
Negative_regulation (blocked) of TrkB associated with antidepressant
7) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.23 Pain Relevance 0.42
In the present study, we further demonstrated that the increased in the protein level of full-length TrkB is completely reversed by concomitant intrathecal injection of BDNF antibody.
Negative_regulation (reversed) of TrkB associated with intrathecal
8) Confidence 0.43 Published 2002 Journal Brain Res. Section Abstract Doc Link 12470870 Disease Relevance 0.55 Pain Relevance 0.76
In saline group, 7,8-DHF and deoxygedunin substantially reduced the immobility time; in contrast, 7,8-DHF and deoxygedunin had no significant effect in mice, when TrkB was blocked by 1NMPP1 (Figure 6B), suggesting that inhibition of the TrkB signaling cascade inhibits the antidepressant effect of these drugs.
Negative_regulation (inhibition) of TrkB associated with antidepressant
9) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.28 Pain Relevance 0.41
The decrease in full-length TrkB would not only affect BDNF-induced signaling but also the supply of BDNF to neurons and, thus, the loss of trophic maintenance of a variety of neuronal types, because the catalytically active full-length TrkB is present predominantly within neuronal axons, cell soma, and dendrites.195 In addition, the undiminished numbers of truncated TrkB would only exacerbate any effects as a result of the loss of catalytically active full-length TrkB, because truncated TrkB inhibits BDNF-mediated neurite outgrowth via the internalization of BDNF.
Negative_regulation (decrease) of TrkB in neurons
10) Confidence 0.41 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.81 Pain Relevance 0.09
The decrease in full-length TrkB would not only affect BDNF-induced signaling but also the supply of BDNF to neurons and, thus, the loss of trophic maintenance of a variety of neuronal types, because the catalytically active full-length TrkB is present predominantly within neuronal axons, cell soma, and dendrites.195 In addition, the undiminished numbers of truncated TrkB would only exacerbate any effects as a result of the loss of catalytically active full-length TrkB, because truncated TrkB inhibits BDNF-mediated neurite outgrowth via the internalization of BDNF.
Negative_regulation (loss) of TrkB in dendrites
11) Confidence 0.41 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.70 Pain Relevance 0.07
Brn3a creates a permissive condition for subtype specification by promoting Runx1 and Runx3 expression, which then refine sensory neuron phenotypes by repressing TrkB in prospective TrkA- and TrkC-expressing neurons, respectively.
Negative_regulation (repressing) of TrkB in neurons
12) Confidence 0.41 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0 Pain Relevance 0
Thus, the timing of the onset of Runx1 expression and of TrkA/B discrimination, as well as the loss of Runx1 and TrkA/B discrimination in Brn3a knockouts, are consistent with a role for Runx1 in the repression of TrkB in TrkA/B precursors.
Negative_regulation (repression) of TrkB associated with repression
13) Confidence 0.40 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.54 Pain Relevance 0.11
The emphasis of recent work on Runx1 has been on its role in late nociceptor development, and the effect of the loss of Runx1 on the initial discrimination of TrkA/TrkB-expressing precursors has not been reported.
Negative_regulation (discrimination) of TrkB in nociceptor associated with nociceptor
14) Confidence 0.40 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.25 Pain Relevance 0.35
If trkB.T1 were functioning solely as a dominant negative inhibitor of signaling in the dorsal horn, the prediction would be that deletion of trkB.T1 would result in more, not less pain.
Negative_regulation (inhibitor) of trkB in dorsal horn associated with pain and dorsal horn
15) Confidence 0.38 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.64 Pain Relevance 0.40
In Runx3 knockout DRG, derepression of trkB seems to be a crucial event, influencing lineage commitment [25,45], and, eventually, resulting in drastic behavioural consequences [16,17].
Negative_regulation (derepression) of trkB associated with targeted disruption and dorsal root ganglion
16) Confidence 0.38 Published 2008 Journal Neural Develop Section Body Doc Link PMC2531103 Disease Relevance 0.61 Pain Relevance 0.23
However, in the TrkbPLC/PLC mice there was a slight reduction in the degree of myelination (Fig. 4C), which was particularly apparent by transmission electron microscopy analysis (TEM) (Fig. 4E-F).
Negative_regulation (reduction) of TrkbPLC
17) Confidence 0.37 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2964534 Disease Relevance 0 Pain Relevance 0
The Trk inhibitor (ARRY-470; Array BioPharma, Boulder, CO) is a potent inhibitor of the tropomyosin kinase family of neurotrophin receptors, demonstrating nanomolar cellular inhibition of TrkA (6.5 nM), TrkB (8.1 nM), and TrkC (10.6 nM) and a high level of selectivity over a panel of kinases run at the ATP Km at 1.0 uM and non-kinase receptors [48](Additional file 1 Table S1 and S2).
Negative_regulation (inhibition) of TrkB
18) Confidence 0.28 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004846 Disease Relevance 0.22 Pain Relevance 0.08
The reduction in TrkB activation by dark-rearing is reported to reverse by 2 hours of light [24], hence could explain the recovery of soma size changes observed in our study.
Negative_regulation (reduction) of TrkB in soma
19) Confidence 0.25 Published 2009 Journal Neural Plasticity Section Body Doc Link PMC2686200 Disease Relevance 0 Pain Relevance 0.07
Furthermore, the receptors TrkB and TrkC are decreased in cholinergic basal forebrain neurons in AD [55].
Negative_regulation (decreased) of TrkB in forebrain associated with disease
20) Confidence 0.19 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 1.12 Pain Relevance 0.28

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