Shuntaro Izawa, Debora Fusca, Hong Jiang, Christian Heilinger, A Christine Hausen, F Thomas Wunderlich, Lukas Steuernagel, Peter Kloppenburg, Jens C Brüning
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Abstract
Orexin/hypocretin receptor type 2 (Ox2R), which is widely expressed in the brain, receives orexin signals and modulates sleep and metabolism. Ox2R selective agonists are currently under clinical trials for narcolepsy treatment. Here, we focused on Ox2R expression and function in melanin-concentrating hormone (MCH) neurons, which have opposite roles to orexin neurons in sleep and metabolism regulation. Ox2R-expressing MCH neurons showed heterogeneity of RNA expression, and orexin B application in brain slices induced both excitatory and inhibitory responses in distinct MCH neuron populations. Ox2R inactivation in MCH neurons reduced transitions from non-rapid eye movement (NREM) to REM sleep and impaired insulin sensitivity with excessive feeding after a fasting period in female mice. In conclusion, Ox2R mediates excitatory and inhibitory responses in MCH neuron sub-populations in vivo, which regulate sleep and metabolism in female mice.
期刊介绍：
Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership.
The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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