論文

査読有り
2014年5月

Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function

JOURNAL OF NEUROSCIENCE
  • Sawako Tabuchi
  • ,
  • Tomomi Tsunematsu
  • ,
  • Sarah W. Black
  • ,
  • Makoto Tominaga
  • ,
  • Megumi Maruyama
  • ,
  • Kazuyo Takagi
  • ,
  • Yasuhiko Minokoshi
  • ,
  • Takeshi Sakurai
  • ,
  • Thomas S. Kilduff
  • ,
  • Akihiro Yamanaka

34
19
開始ページ
6495
終了ページ
6509
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1523/JNEUROSCI.0073-14.2014
出版者・発行元
SOC NEUROSCIENCE

The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/ hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal orexin-tTA; TetO DTA mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when similar to 5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, orexin-tTA; TetO DTA mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.

リンク情報
DOI
https://doi.org/10.1523/JNEUROSCI.0073-14.2014
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24806676
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000336380500009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1523/JNEUROSCI.0073-14.2014
  • ISSN : 0270-6474
  • PubMed ID : 24806676
  • Web of Science ID : WOS:000336380500009

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