INT106057

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Context Info
Confidence 0.57
First Reported 2002
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 27
Total Number 28
Disease Relevance 15.50
Pain Relevance 3.47

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

endoplasmic reticulum (Hcrt) cytoplasm (Hcrt)
Anatomy Link Frequency
neurons 5
pons 2
cerebrospinal fluid 2
cortex 2
puncture 1
Hcrt (Mus musculus)
Pain Link Frequency Relevance Heat
Catecholamine 22 100.00 Very High Very High Very High
Cannabinoid 20 99.76 Very High Very High Very High
Enkephalin 2 99.76 Very High Very High Very High
Neuropeptide 70 99.60 Very High Very High Very High
Glutamate receptor 2 99.40 Very High Very High Very High
antagonist 12 98.64 Very High Very High Very High
Dopamine 47 98.20 Very High Very High Very High
agonist 9 94.96 High High
Glutamate 4 94.04 High High
Locus ceruleus 184 91.20 High High
Disease Link Frequency Relevance Heat
Sleep Disorders 1543 99.96 Very High Very High Very High
Idiopathic Hypersomnolence 25 99.72 Very High Very High Very High
Hypersomnia 125 99.26 Very High Very High Very High
Targeted Disruption 837 99.16 Very High Very High Very High
Hyperglycemia 18 98.96 Very High Very High Very High
Lumbar Puncture Related Headaches 1 98.74 Very High Very High Very High
Congenital Anomalies 20 98.08 Very High Very High Very High
Cognitive Disorder 5 97.08 Very High Very High Very High
Disease 85 93.52 High High
Death 180 88.84 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Narcolepsy with cataplexy is associated with a deficiency of orexin-A, also known as hypocretin-1, a hypothalamic peptide implicated in energy homeostasis and arousal (Sakurai 2007).


Negative_regulation (deficiency) of orexin-A associated with hypersomnia and sleep disorders
1) Confidence 0.57 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761173 Disease Relevance 1.17 Pain Relevance 0.11
In humans, loss of HCRT neurons is associated with the sleep disorder narcolepsy and inappropriate triggering of REM sleep [1], [2].
Negative_regulation (loss) of HCRT in neurons associated with sleep disorders
2) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.44 Pain Relevance 0.04
Immunohistochemical studies also revealed more than 90% decrease in HCRT cell counts in the hypothalamus of narcoleptic subjects [8].
Negative_regulation (decrease) of HCRT in hypothalamus
3) Confidence 0.46 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.54 Pain Relevance 0.03
Because lesions of these areas and/or a hypocretin deficiency typically increase REM sleep at night, it will be important to determine the effects such lesions in diurnal rodents.


Negative_regulation (deficiency) of hypocretin
4) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.08 Pain Relevance 0.17
Indeed, even in mice lacking both HCRT and the norepinephrine synthesizing enzyme, dopamine beta hydroxylase, i.e., a double knockout, there is no additive effect [38].
Negative_regulation (lacking) of HCRT associated with targeted disruption and dopamine
5) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.22 Pain Relevance 0.26
Age-related decline in hypocretin (orexin) receptor 2 messenger RNA levels in the mouse brain.
Negative_regulation (decline) of hypocretin in brain associated with enkephalin
6) Confidence 0.42 Published 2002 Journal Neurosci. Lett. Section Title Doc Link 12399012 Disease Relevance 0 Pain Relevance 0.34
A lumbar puncture was performed in 35 patients (19 NC, 7 NWC, 9 HI) in order to measure the CSF hypocretin-1/orexin A levels.
Negative_regulation (measure) of orexin A in puncture associated with idiopathic hypersomnolence, sleep disorders and lumbar puncture related headaches
7) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2954157 Disease Relevance 1.08 Pain Relevance 0
Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons.
Negative_regulation (inhibition) of hypocretin in neurons associated with catecholamine and neuropeptide
8) Confidence 0.41 Published 2005 Journal J. Neurosci. Section Title Doc Link 15634779 Disease Relevance 0.09 Pain Relevance 0.43
Over 90% of narcolepsy-cataplexy cases are associated with a dramatic decrease in hypocretin-1 (HCRT1) in the cerebrospinal fluid [2].
Negative_regulation (decrease) of hypocretin-1 in cerebrospinal fluid associated with sleep disorders
9) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 1.23 Pain Relevance 0.05
Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown.
Negative_regulation (loss) of hypocretin associated with sleep disorders
10) Confidence 0.39 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2617764 Disease Relevance 0.50 Pain Relevance 0.05
All neurons showing colocalization of IGFBP3 and HCRT appeared to have a reduced hypocretin signal.
Negative_regulation (reduced) of hypocretin in neurons
11) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.23 Pain Relevance 0.06
Over 90% of narcolepsy-cataplexy cases are associated with a dramatic decrease in hypocretin-1 (HCRT1) in the cerebrospinal fluid [2].
Negative_regulation (decrease) of HCRT1 in cerebrospinal fluid associated with sleep disorders
12) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 1.23 Pain Relevance 0.05
Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decreased hypocretin promotor activity in the presence of excessive IGFBP3.
Negative_regulation (decreased) of hypocretin associated with targeted disruption
13) Confidence 0.39 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2617764 Disease Relevance 0.73 Pain Relevance 0.03
Although these effects could be indirectly mediated by minor endocrine abnormalities in these animals, for example hyperglycemia [33], the in vitro findings that IGFBP3 expression suppresses HCRT promotor activity (Fig. 3E) and that the functional IGFBP3 polymorphism rs2854744 is associated with reduced hypocretin transmission, observed as lower levels of Hcrt-1 in human CSF (Fig. 3F), makes this hypothesis unlikely.
Negative_regulation (suppresses) of HCRT associated with hyperglycemia and congenital anomalies
14) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.85 Pain Relevance 0.04
Furthermore, the concentrations of HCRT1 and HCRT2 in the cortex and pons, two areas with HCRT projections, are dramatically decreased [7].
Negative_regulation (decreased) of HCRT1 in cortex
15) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.65 Pain Relevance 0.03
Furthermore, the concentrations of HCRT1 and HCRT2 in the cortex and pons, two areas with HCRT projections, are dramatically decreased [7].
Negative_regulation (decreased) of HCRT2 in cortex
16) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.64 Pain Relevance 0.03
In HCRT-ko mice loss of NeuN staining demarcated the lesioned area and traced onto paper using a drawing tube attached to a microscope (Nikon Eclipse E400).


Negative_regulation (loss) of HCRT-ko in tube
17) Confidence 0.36 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.34 Pain Relevance 0.03
This striking result suggests that if this precise neuroanatomical region had been targeted, it would have been possible to discover the central feature of narcolepsy -HCRT deficiency- without a preconceived hypothesis.
Spec (possible) Negative_regulation (deficiency) of HCRT associated with sleep disorders
18) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.42 Pain Relevance 0.04
Immunocytochemistry did not reveal hypocretin cell defects nor decrease in cell number in Igfbp3 knockout or transgenic animals (data not shown).
Neg (nor) Negative_regulation (decrease) of hypocretin associated with targeted disruption
19) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 1.57 Pain Relevance 0
Identification of transcripts downregulated in the hypocretin-ataxin-3 hemizygous transgenic mouse model
Negative_regulation (downregulated) of hypocretin associated with targeted disruption
20) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.35 Pain Relevance 0.06

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