INT117585

Context Info Confidence 0.56 First Reported 2004 Last Reported 2010 Negated 0 Speculated 4 Reported most in Body Documents 10 Total Number 17 Disease Relevance 6.16 Pain Relevance 1.77

endoplasmic reticulum (Hcrt) cytoplasm (Hcrt)

Anatomy Link Frequency neurons 7 dorsal 1 stomach 1 Hcrt (Mus musculus)

Pain Link Frequency Relevance Heat Neuropeptide 51 100.00 Glutamate receptor 3 99.74 Cannabinoid 10 99.70 antagonist 6 97.48 Locus ceruleus 66 96.56 Central nervous system 9 96.48 Glutamate 6 94.68 agonist 7 89.32 tetrodotoxin 6 88.56 medulla 19 70.00

Disease Link Frequency Relevance Heat Sleep Disorders 532 99.56 Targeted Disruption 322 96.72 Apoptosis 124 96.72 Spinal Cord Injury 116 94.68 Neuroblastoma 14 91.08 Apnoea 2 87.04 Syndrome 2 85.04 Death 118 83.88 Gliosis 7 80.76 Cognitive Disorder 2 75.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

IGFBP3, together with IGF, is to be added to the growing list of metabolic indicators that have been reported to regulate hypocretin activity.

Regulation (regulate) of hypocretin

1) Confidence 0.56 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.20 Pain Relevance 0

One gene in particular, hypocretin (orexin) neuropeptide precursor (HcRt), is known to regulate energy metabolism in neurons [54,55], among other functions, and, is significantly down-regulated in LDPT neurons but up-regulated in TPS neurons following axotomy.

Regulation (regulated) of orexin in neurons associated with neuropeptide

2) Confidence 0.44 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC3001741 Disease Relevance 0.24 Pain Relevance 0.05

One gene in particular, hypocretin (orexin) neuropeptide precursor (HcRt), is known to regulate energy metabolism in neurons [54,55], among other functions, and, is significantly down-regulated in LDPT neurons but up-regulated in TPS neurons following axotomy.

Regulation (regulated) of orexin in neurons associated with neuropeptide

3) Confidence 0.44 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC3001741 Disease Relevance 0.24 Pain Relevance 0.05

One gene in particular, hypocretin (orexin) neuropeptide precursor (HcRt), is known to regulate energy metabolism in neurons [54,55], among other functions, and, is significantly down-regulated in LDPT neurons but up-regulated in TPS neurons following axotomy.

Regulation (regulated) of hypocretin in neurons associated with neuropeptide

4) Confidence 0.44 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC3001741 Disease Relevance 0.24 Pain Relevance 0.05

The present study was aimed to investigate the influence of orexin A (OXA) on the mechanical activity of fundal and antral strips of the mouse stomach.

Spec (investigate) Regulation (influence) of orexin A in stomach

5) Confidence 0.44 Published 2008 Journal Regul. Pept. Section Abstract Doc Link 17881068 Disease Relevance 0.06 Pain Relevance 0.32

One gene in particular, hypocretin (orexin) neuropeptide precursor (HcRt), is known to regulate energy metabolism in neurons [54,55], among other functions, and, is significantly down-regulated in LDPT neurons but up-regulated in TPS neurons following axotomy.

Regulation (regulated) of hypocretin in neurons associated with neuropeptide

6) Confidence 0.44 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC3001741 Disease Relevance 0.24 Pain Relevance 0.05

Deficient HCRT neurotransmission is sufficient to produce narcolepsy, as animal models with dysregulated HCRT transmission exhibit a narcolepsy-like phenotype [4], [5].

Regulation (dysregulated) of HCRT associated with sleep disorders

7) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 1.16 Pain Relevance 0.04

We next characterized whether overexpression of IGFBP3 and resulting effects on hypocretin transmission affect sleep and wakefulness by conducting sleep studies on hIGFBP3 transgenic mice and their littermates.

Spec (whether) Regulation (effects) of hypocretin associated with targeted disruption

8) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.74 Pain Relevance 0

(corresponds to the first exon sequence just before the translation initiator ATG of human prepro-Hcrt gene, and 5?

Regulation (corresponds) of Hcrt

9) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.28 Pain Relevance 0

Genetic studies in an autosomal recessive canine model of narcolepsy and in gene-targeted mice have identified the hypothalamic hypocretin (orexin) neuropeptide system as a key target for human narcolepsy.

Regulation (target) of hypocretin associated with neuropeptide and sleep disorders

10) Confidence 0.26 Published 2004 Journal Minerva Med. Section Abstract Doc Link 15289749 Disease Relevance 0.82 Pain Relevance 0.12

Circadian and dark-pulse activation of orexin/hypocretin neurons Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits.

Regulation (control) of hypocretin in neurons

11) Confidence 0.26 Published 2008 Journal Mol Brain Section Title Doc Link PMC2632999 Disease Relevance 0 Pain Relevance 0.03

We studied the actions of group III metabotropic glutamate receptors (mGluRs) in modulating the activity of hypocretin neurons using whole-cell voltage- and current-clamp recording in mouse whole hypothalamic slices or minislices consisting only of the lateral hypothalamus.

Regulation (modulating) of hypocretin in neurons associated with glutamate receptor

12) Confidence 0.25 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15044540 Disease Relevance 0 Pain Relevance 0.24

To test whether IGFBP3 activity regulates hypocretin levels in vivo, DNA samples of 262 Caucasian subjects with normal CSF hypocretin-1 levels (>200 pg/ml), either drawn from healthy control subjects or from subjects with a complaint of sleepiness unexplained by hypocretin deficiency, were typed for rs2854744 (?

Spec (whether) Regulation (regulates) of hypocretin associated with sleep disorders

13) Confidence 0.25 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.44 Pain Relevance 0

A deeper understanding of HCRT cell physiology is required, including the identification of genes and proteins that may be the target of an autoimmune attack or may modulate hypocretin expression/metabolism to make this cell population more susceptible to potential apoptosis.

Spec (may) Regulation (modulate) of hypocretin associated with apoptosis

14) Confidence 0.25 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.37 Pain Relevance 0

One hypothesized hypocretin target in the pons is the ventral sub lateral-dorsal region (vSLD), which is ventral to the locus coeruleus [11].

Regulation (target) of hypocretin in dorsal associated with locus ceruleus

15) Confidence 0.23 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.40 Pain Relevance 0.08

DNA samples from 130 parent-child trios (proband and parents), and 252 individuals with available CSF hypocretin level values in the control range, were obtained and used.

Regulation (values) of hypocretin

16) Confidence 0.21 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 0.66 Pain Relevance 0.07

Together, these results show that cannabinoids have opposite effects on MCH and hypocretin neurons.

Regulation (effects) of hypocretin in neurons associated with cannabinoid

17) Confidence 0.18 Published 2007 Journal J. Neurosci. Section Abstract Doc Link 17475795 Disease Relevance 0.07 Pain Relevance 0.66

General Comments

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