Review
Neurosciences
Liam E. Potter, Christian R. Burgess
Summary: Given the impact of sleep disorders on health, researchers are exploring novel avenues of treatment, including targeting the melanin-concentrating hormone (MCH) system. This system has been implicated in sleep regulation and various physiological functions, but skepticism remains regarding the development of MCH-targeting drugs. Additional research is needed to fully understand the role of the MCH system in sleep regulation and address drug design challenges.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Yuki Kobayashi, Tomoya Okada, Daisuke Miki, Yuko Sekino, Noriko Koganezawa, Tomoaki Shirao, Giovanne B. Diniz, Yumiko Saito
Summary: The primary cilium is a sensitive signaling hub in cells, capable of changing length to ensure efficient signaling capacity. In hippocampal neurons, MCH triggers cilia length reduction via MCHR1-mediated Gi/o and Akt signaling pathways.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Maria Sotelo, Jean Tyan, Chelsea Markunas, Bibi A. Sulaman, Lorraine Horwitz, Hankyu Lee, Joshua G. Morrow, Gideon Rothschild, Bo Duan, Ada Eban-Rothschild
Summary: The transition from wakefulness to sleep involves specific behaviors, such as nest-building and grooming, which are associated with stereotypic electroencephalogram (EEG) patterns. The ability to build a nest promotes sleep initiation and consolidation, while the lack of nesting material disrupts sleep. Neuronal ensembles in the lateral hypothalamus regulate the motivation to engage in nest-building behavior and control sleep initiation and intensity.
Article
Endocrinology & Metabolism
Meng Wang, Yue Zhai, Xiaowei Lei, Jing Xu, Bopei Jiang, Zhe Kuang, Cong Zhang, Shangyun Liu, Shan Bian, Xiao-Mei Yang, Tao Zan, Li-Na Jin, Qingfeng Li, Chao Zhang
Summary: This study investigated the interaction between MRAP2 and MCHR1, and found that MRAP2 could inhibit the signaling of MCHR1. Functional truncation experiments revealed the importance of the C-terminal domains of MRAP2 in pharmacological modulation. These findings elucidated the broad regulatory profile of MRAP2 in the central nervous system.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Wedad Alhassen, Yuki Kobayashi, Jessica Su, Brianna Robbins, Henry Nguyen, Thant Myint, Micah Yu, Surya M. Nauli, Yumiko Saito, Amal Alachkar
Summary: The MCH system plays a crucial role in regulating the length of brain neuronal primary cilia, with activation causing cilia shortening and inactivation leading to cilia lengthening. This suggests that MCHR1 at primary cilia could be a potential therapeutic target for conditions associated with impaired primary cilia function.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Neurosciences
Cristina Concetti, Denis Burdakov
Summary: The lateral hypothalamus plays a role in sleep-wake control by producing orexin/hypocretin and melanin-concentrating hormone neuropeptides. These neuropeptides can rapidly change their firing in response to external stimuli in awake animals. Optogenetic and chemogenetic manipulations suggest that rapid lateral hypothalamic dynamics shape cognitive and motor processes in the awake brain.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Ronald McGregor, Alessandra Matzeu, Thomas C. Thannickal, Frank Wu, Marcia Cornford, Remi Martin-Fardon, Jerome M. Siegel
Summary: Heroin addicts and mice administered morphine for a 2 week period demonstrated an increase in hypothalamic hypocretin (Hcrt or orexin) producing neurons, while also showing a decrease in Hcrt cell size. Similarly, male rats addicted to cocaine showed an increased number of detectable Hcrt neurons. On the other hand, humans with alcohol use disorder (AUD) exhibited a decrease in the number and size of detectable Hcrt neurons, as well as a reduction in the size of intermingled melanin concentrating hormone (MCH) neurons. The present study highlights significant differences in the response of Hcrt neurons to opioids and alcohol in individuals with substance abuse history.
Article
Chemistry, Medicinal
Jozsef Huszar, Eva Bozo, Gyula Beke, Krisztina Katalin Szalai, Peter Kardos, Andras Boros, Istvan Greiner, Janos Eles
Summary: Obesity is a global epidemic associated with severe diseases, and pharmacotherapies including MCHR1 antagonists have been investigated. This study designed and synthesized novel MCHR1 antagonists based on benzofuro-pyridine and pyrazino-indole scaffold, and successfully developed compounds with excellent in vitro parameters that can be considered as valuable tools for further pharmacological investigation.
Article
Fisheries
Haruhisa Fukada, Noriko Hosomi, Haruka Morino, Toshiro Masumoto
Summary: The results of two experiments suggest that the levels of NPY and MCH1 in yellowtail are mainly regulated by serum glucose concentration derived from feed, and they function as feeding stimulators.
Article
Neurosciences
Sara Calafate, Gokhan Ozturan, Nicola Thrupp, Jeroen Vanderlinden, Luisa Santa-Marinha, Rafaela Morais-Ribeiro, Antonella Ruggiero, Ivan Bozic, Thomas Rusterholz, Blanca Lorente-Echeverria, Marcelo Dias, Wei-Ting Chen, Mark Fiers, Ashley Lu, Ine Vlaeminck, Eline Creemers, Katleen Craessaerts, Joris de Wit, Luuk van Boekholdt, Suresh Poovathingal, Kristofer Davie, Dietmar Rudolf Thal, Keimpe Wierda, Tiago Gil Oliveira, Inna Slutsky, Antoine Adamantidis, Bart De Strooper, Joris de Wit
Summary: Early AD is characterized by hippocampal hyperactivity and decreased sleep quality. The MCH system is involved in neuronal homeostasis but fails in the early stages of AD, leading to aberrant excitatory drive and sleep defects that compromise hippocampus-dependent functions.
NATURE NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Xiaoman He, Yuhang Li, Nana Zhang, Jinfang Huang, Xing Ming, Ruixiao Guo, Yang Hu, Pengfei Ji, Feifei Guo
Summary: The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area (LHA) project to the basolateral amygdala (BLA) and play a role in regulating anxiety-like behavior in mice. Chronic acute combining stress (CACS) leads to anxiety-like behavior and intestinal dysfunction, which can be improved by blocking MCH receptor 1 (MCHR1) and regulating intestinal permeability and inflammation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gyutae Lim, Ka Young You, Jeong Hyun Lee, Moon Kook Jeon, Byung Ho Lee, Jae Yong Ryu, Kwang-Seok Oh
Summary: This study identified a potent MCHR1 antagonist, KRX-104130, with no cardiotoxicity using machine learning prediction models. The study also explored the potential of KRX-104130 for treating nonalcoholic steatohepatitis (NASH) and confirmed its therapeutic effects in a NASH mouse model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Oscar Gonzalez-Flores, James G. Pfaus, Ailyn Luna-Hernandez, Omar Montes-Narvaez, Raymundo Dominguez-Ordonez, Miriam B. Tecamachaltzi-Silvaran, Marcos Garcia-Juarez
Summary: This study aimed to investigate the hypothesis that the Kiss and MCH pathways regulate female sexual behavior induced by steroid hormones. The results showed that the administration of Kiss inhibitor and MCH significantly reduced lordosis behavior induced by hormonal stimulation, supporting the hypothesis.
HORMONES AND BEHAVIOR
(2022)
Article
Clinical Neurology
Guo-Qing Chang, Nushrat Yasmin, Adam D. Collier, Olga Karatayev, Nailya Khalizova, Amanda Onoichenco, Milisia Fam, Avi S. Albeg, Samantha Campbell, Sarah F. Leibowitz
Summary: Prenatal alcohol exposure (PAE) increases alcohol consumption and the risk for alcohol use disorder. The study investigates the role of fibroblast growth factor 2 (FGF2) and its receptor FGFR1 in mediating the PAE-induced increase in melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus. Results show that PAE stimulates FGF2 and FGFR1 gene expression and increases the density of MCH neurons in a sex-dependent manner, supporting the involvement of the FGF2-FGFR1 system in mediating the PAE-induced increase in MCH neurons.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Jyoti Kumbar, C. B. Ganesh
Summary: The study revealed that melanin-concentrating hormone (MCH) blocks follicular development during the ovarian cycle in female tilapia Oreochromis mossambicus, possibly through the suppression of the GnRH-LH axis, and may activate the stress-axis pathway in fish.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2022)
