Get the latest biotech news where you want it. Sign up for the free GenePool newsletter today!
(Kanazawa, Japan, 25 June 2013) One of Kanazawa University’s leading professors has spent the last 15 years investigating the role of orexin neuropeptides in the brain. Takeshi Sakurai’s work is furthering understanding of sleep and wakeful states and leading to the development of new therapies for insomnia and narcolepsy. This research is also described in the inaugural June issue of the Kanazawa University Research Bulletin: http://www.kanazawa-u.ac.jp/research_bulletin/index.html
In 1998, during a postdoc at the University of Texas, Sakurai discovered orexin A and orexin B – two neuropeptides in the hypothalamus region of rat brains2. His team found that the orexins acted as regulators of feeding behaviour in the animals.
“I discovered orexin while searching for endogenous peptide ligands for orphan G-protein receptors,” explains Sakurai. “Since then, I have been working on the physiological roles of orexin, completing intensive studies of orexin-producing neurons.”
Following on from the initial studies into the role of orexin in feeding behaviour, Sakurai proved that the neuropeptides were responsible for triggering wakefulness in order to search for food. Sakurai found that orexin-deficient mice failed to become active or look for food after a period of fasting3,4.
“Orexin is a critical factor in maintaining and ensuring the stability of wakefulness in the brain, and they interact with systems that regulate emotion, reward and energy balance in the body,” states Sakurai5. “Orexin receptors are expressed by neurons in the regions involved in the regulation of arousal, and orexin peptides basically activate these cells. We have since discovered that sleep disorders such as narcolepsy and insomnia are caused by the under- and over-activation of orexins.”
Sakurai and co-workers at Kanazawa University, together with researchers in the USA, have recently revealed the functions of orexin receptors Ox1R and Ox2R4. Each of these receptors is now understood to have distinct pathways influencing REM and non-REM sleep patterns, with Ox2R having the most pivotal role.
“From these findings, pharmaceutical companies have now developed orexin receptor antagonists for insomnia treatment,” explains Sakurai. “Agonists for Ox2R are sought to create therapies for narcolepsy and other sleep problems. We are planning to investigate the receptors in greater detail in order to shed more light on the mechanisms behind orexin activity.”
Publication and Affiliation
1. Takeshi Sakuraia* & Michihiro Mieda. Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal. Trends in Pharmacological Sciences, 32(8) (2011)
2. Takeshi Sakurai et al. Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92 (1998)
3. Akihiro Yamanaka et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 32 (2003)
4. Junko Hara et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30 (2001)
5. Takeshi Sakurai et al. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron 46 (2005)
6. Michihiro Mieda et al. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. Journal of Neuroscience 31 (17) (2011) doi: 10.10161/j.tips.2011.03.007
a. Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, Japan
Takeshi Sakurai first discovered orexin A and B neuropeptides in 1998, and since then has studied their morphology and function with regards to sleep / wake states in the brain. His research has led to the development of treatment for sleep disorders such as insomnia.
Further information
Organization of Frontier Science and Innovation
Kanazawa University
Kakuma, Kanazawa, Ishikawa 920-1192, Japan
E-mail: fsojimu@adm.kanazawa-u.ac.jp
Website: http://www.o-fsi.kanazawa-u.ac.jp/en/about/
About Kanazawa University
As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 16 schools offering courses in subjects that include medicine, computer engineering, and humanities.
The University is located on the coast of the Sea of Japan in Kanazawa—a city rich in history and culture. The city of Kanazawa has cultivated a highly respected intellectual profile since the time of the Kaga fiefdom (1598–1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 12,200 students including 500 from overseas.
Kanazawa University website: http://www.kanazawa-u.ac.jp/e/index.html
Help employers find you! Check out all the jobs and post your resume.
