Hypocretin/orexin prevents recovery from sickness

Tanaka,Susumu; Toyoda,Hiromi; Honda,Yoshiko; Seki,Yasuko; Sakurai,Takeshi; Honda,Kazuki; Kodama,Tohru

doi:10.3892/br.2015.491

September-2015 Volume 3 Issue 5

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September-2015 Volume 3 Issue 5

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Article

Hypocretin/orexin prevents recovery from sickness

Authors:
- Susumu Tanaka
- Hiromi Toyoda
- Yoshiko Honda
- Yasuko Seki
- Takeshi Sakurai
- Kazuki Honda
- Tohru Kodama
View Affiliations / Copyright

Affiliations: Sleep Disorders Project, Department of Psychiatry and Behavioral Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 156‑8506, Japan, Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa 920‑8640, Japan
Pages: 648-650
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Published online on: July 17, 2015

https://doi.org/10.3892/br.2015.491
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Abstract

Sickness behavior is defined as states of lethargy, depression, anxiety, loss of appetite, hypersomnia, hyperalgesia, reduction of grooming and failure to concentrate that can be induced by inflammatory diseases, such as infections and cancer. Recent findings revealed that the lipopolysaccharide (LPS) injection causes lethargy as a consequence of the inhibition of hypocretin signaling. The hypocretin system maintains the vigilance state in various physiological processes. In order to investigate the sleep arousal system against sickness behavior, LPS‑induced sickness behavior was examined in hypocretin‑ataxin‑3 transgenic mice, whose hypocretin neurons were postnatally ablated. Sleep‑wake activity was determined following the administration of LPS at Zeitgeber time (ZT) 8.0 in ataxin‑3 transgenic mice, and the age‑, gender‑matched wild‑type littermates. LPS injection induced increases in non‑rapid eye movement (REM) sleep in the matched wild‑type littermates. In addition, a further increase in periods of sleep according to the loss of hypocretin neurons was identified in the ataxin‑3 transgenic mice. A marked reduction of awakening during ZT12‑ZT18 was observed as expected following LPS injection in the mouse lines. The increase in the period of non‑REM sleep was not observed on the next day following LPS administration in either of the mouse lines. Complete recovery of physical activity was not observed in the matched wild‑type littermates. Ataxin‑3 transgenic mice recovered their physical activity to the same level as that on the first day before LPS administration. These results suggest the possibility that a faster recovery is the result of deeper resting according to the absence of hypocretin neurons, as ataxin‑3 transgenic mice demonstrated more non-REM sleep.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Hypocretin/orexin prevents recovery from sickness

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