INT110139

Context Info Confidence 0.67 First Reported 2003 Last Reported 2009 Negated 0 Speculated 1 Reported most in Abstract Documents 7 Total Number 8 Disease Relevance 2.14 Pain Relevance 2.26

endoplasmic reticulum (Hcrt) cytoplasm (Hcrt)

Anatomy Link Frequency neurons 5 Hcrt (Mus musculus)

Pain Link Frequency Relevance Heat withdrawal 5 98.80 Morphine 7 98.64 antagonist 4 90.80 opiate 1 90.36 addiction 2 89.84 mu opioid receptor 1 88.04 tetrodotoxin 2 83.88 gABA 22 81.20 Glutamate 8 80.80 amygdala 4 79.72

Disease Link Frequency Relevance Heat Death 20 99.76 Sleep Disorders 184 99.40 Targeted Disruption 104 98.92 Morphine Dependence 2 90.56 Opiate Addiction 1 84.56 Injury 2 70.16 Congenital Anomalies 2 67.60 Hyperglycemia 2 64.08 Apoptosis 8 58.84 Cancer 6 33.16

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship.

Positive_regulation (activation) of hypocretin in neurons

1) Confidence 0.67 Published 2008 Journal Mol Brain Section Abstract Doc Link PMC2632999 Disease Relevance 0 Pain Relevance 0.04

Indeed, the HCRT neurons are activated by low glucose levels and shut-off when the glucose levels increase [35].

Positive_regulation (activated) of HCRT in neurons

2) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2709920 Disease Relevance 0.05 Pain Relevance 0.19

Glutamatergic interneurons have been suggested to play a role in a positive feedback recruitment of hypocretin on hypocretin neurons. l-AP-4 blocked hypocretin-mediated increases in EPSCs and attenuated the hypocretin-mediated increase in spike frequency.

Positive_regulation (recruitment) of hypocretin in neurons

3) Confidence 0.46 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15044540 Disease Relevance 0 Pain Relevance 0.38

Glutamatergic interneurons have been suggested to play a role in a positive feedback recruitment of hypocretin on hypocretin neurons. l-AP-4 blocked hypocretin-mediated increases in EPSCs and attenuated the hypocretin-mediated increase in spike frequency.

Positive_regulation (recruitment) of hypocretin in neurons

4) Confidence 0.46 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15044540 Disease Relevance 0 Pain Relevance 0.38

The results above do not support the involvement of IGFBP3 in causing hypocretin cell death in narcolepsy.

Positive_regulation (causing) of hypocretin associated with sleep disorders and death

5) Confidence 0.45 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2617764 Disease Relevance 1.02 Pain Relevance 0.03

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.

Positive_regulation (activation) of hypocretin in neurons

6) Confidence 0.45 Published 2008 Journal Mol Brain Section Title Doc Link PMC2632999 Disease Relevance 0 Pain Relevance 0.03

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.

Spec (possibly) Positive_regulation (mediated) of hypocretin associated with targeted disruption

7) Confidence 0.42 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2617764 Disease Relevance 0.73 Pain Relevance 0.03

Additionally, c-Fos and the orexin gene itself are induced in orexin cells in the LH during morphine withdrawal.

Positive_regulation (induced) of orexin gene associated with withdrawal and morphine

8) Confidence 0.19 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12716916 Disease Relevance 0.34 Pain Relevance 1.18

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