ArticleNeurobiology of disease2018
Melanin-concentrating hormone neurons contribute to dysregulation of rapid eye movement sleep in narcolepsy.
Article in Neurobiology of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Oxytocin promotes socially triggered cataplexy.Nature neuroscience · 2026Article
- Orexins and neuregulins as exemplars of peptide physiology in the brain: experimental challenges and implications for neuropathology.Frontiers in cellular neuroscience · 2026Article
- Current knowledge on the pathophysiology of idiopathic hypersomnia and potential mechanisms of action for low-sodium oxybate treatment.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Review
- Article
- The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance.Frontiers in neuroscience · 2025Review
- Effects of mild cognitive impairment and sleep disorders on the minimum alveolar concentration value of sevoflurane.BMC anesthesiology · 2024Article
- Neural Control of REM Sleep and Motor Atonia: Current Perspectives.Current neurology and neuroscience reports · 2023Review
- Article
- A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy.Cell discovery · 2022Article
- Identification and New Indication of Melanin-Concentrating Hormone Receptor 1 (MCHR1) Antagonist Derived from Machine Learning and Transcriptome-Based Drug Repositioning Approaches.International journal of molecular sciences · 2022Article
- Melanin-concentrating hormone promotes anxiety and intestinal dysfunctionFrontiers in pharmacology · 2022Article
- Regulation of Brain Primary Cilia Length by MCH Signaling: Evidence from Pharmacological, Genetic, Optogenetic, and Chemogenic Manipulations.Molecular neurobiology · 2022Article
- Recent advances in neuropeptide-related omics and gene editing: Spotlight on NPY and somatostatin and their roles in growth and food intake of fish.Frontiers in endocrinology · 2022Review
- Selective activation of the hypothalamic orexinergic but not melanin-concentrating hormone neurons following pilocarpine-induced seizures in rats.Frontiers in neuroscience · 2022Article
- The melanin-concentrating hormone system as a target for the treatment of sleep disorders.Frontiers in neuroscience · 2022Review
- MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice.Molecules (Basel, Switzerland) · 2021Article
- Sleep-Wake Control by Melanin-Concentrating Hormone (MCH) Neurons: a Review of Recent Findings.Current neurology and neuroscience reports · 2020Review
- Article
- Article
- A circuit perspective on narcolepsy.Sleep · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The lateral hypothalamus contains neurons producing orexins that promote wakefulness and suppress REM sleep as well as neurons producing melanin-concentrating hormone (MCH) that likely promote REM sleep. Narcolepsy with cataplexy is caused by selective loss of the orexin neurons, and the MCH neurons appear unaffected. As the orexin and MCH systems exert opposing effects on REM sleep, we hypothesized that imbalance in this REM sleep-regulating system due to activity in the MCH neurons may contribute to the striking REM sleep dysfunction characteristic of narcolepsy. To test this hypothesis, we chemogenetically activated the MCH neurons and pharmacologically blocked MCH signaling in a murine model of narcolepsy and studied the effects on sleep-wake behavior and cataplexy. To chemoactivate MCH neurons, we injected an adeno-associated viral vector containing the hM3Dq stimulatory DREADD into the lateral hypothalamus of orexin null mice that also express Cre recombinase in the MCH neurons (MCH-Cre::OX-KO mice) and into control MCH-Cre mice with normal orexin expression. In both lines of mice, activation of MCH neurons by clozapine-N-oxide (CNO) increased rapid eye movement (REM) sleep without altering other states. In mice lacking orexins, activation of the MCH neurons also increased abnormal intrusions of REM sleep manifest as cataplexy and short latency transitions into REM sleep (SLREM). Conversely, a MCH receptor 1 antagonist, SNAP 94847, almost completely eliminated SLREM and cataplexy in OX-KO mice. These findings affirm that MCH neurons promote REM sleep under normal circumstances, and their activity in mice lacking orexins likely triggers abnormal intrusions of REM sleep into non-REM sleep and wake, resulting in the SLREM and cataplexy characteristic of narcolepsy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.