Sleep-Wake Control by Melanin-Concentrating Hormone (MCH) Neurons: a Review of Recent Findings
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(2020) 20:55
SLEEP (M. THORPY, SECTION EDITOR)
Sleep-Wake Control by Melanin-Concentrating Hormone (MCH) Neurons: a Review of Recent Findings Sathyajit S. Bandaru 1 & Mudasir A. Khanday 1,2 & Nazifa Ibrahim 1,3 & Fumito Naganuma 1,4 & Ramalingam Vetrivelan 1,2 Accepted: 17 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of the Review Melanin-concentrating hormone (MCH)–expressing neurons located in the lateral hypothalamus are considered as an integral component of sleep-wake circuitry. However, the precise role of MCH neurons in sleep-wake regulation has remained unclear, despite several years of research employing a wide range of techniques. We review recent data on this aspect, which are mostly inconsistent, and propose a novel role for MCH neurons in sleep regulation. Recent Findings While almost all studies using “gain-of-function” approaches show an increase in rapid eye movement sleep (or paradoxical sleep; PS), loss-of-function approaches have not shown reductions in PS. Similarly, the reported changes in wakefulness or non-rapid eye movement sleep (slow-wave sleep; SWS) with manipulation of the MCH system using conditional genetic methods are inconsistent. Summary Currently available data do not support a role for MCH neurons in spontaneous sleep-wake but imply a crucial role for them in orchestrating sleep-wake responses to changes in external and internal environments. Keywords Rapid eye movement sleep . Paradoxical sleep . Energy balance . Body temperature optogenetics . Chemogenetics
Introduction Melanin-concentrating hormone (MCH) was originally investigated in teleost fish for its effect on skin pigmentation and was later found to be present in the central nervous system (CNS) of all vertebrates, ranging from lampreys to humans [1–4]. MCH is a 19-amino acid cyclic peptide in mammals, and the peptide sequence is identical in humans and rodents [5]. MCH neurons are primarily located in the lateral Sathyajit S. Bandaru and Mudasir A. Khanday contributed equally to this work. This article is part of the Topical Collection on Sleep * Ramalingam Vetrivelan [email protected] 1
Department of Neurology, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Center for Life Science # 711, Boston, MA, USA
2
Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
3
Department of Public Health Sciences, University of Massachusetts, Amherst, MA, USA
4
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan
hypothalamus (LH), zona incerta (ZI), and the dorsomedial hypothalamus but are also found in the olfactory tubercle and the paramedian reticular formation in small numbers [6]. In addition to these locations in both sexes, MCH neurons are found in the lateral tegmental nucleus of female rats [7]. During the post-partum period, MCH is transiently expressed in many neurons in the medial preoptic area and rostral paraventricular hypothalamus, although this expression disappears
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