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Peripheral actions and direct central-local communications of melanocortin 4 receptor signaling

Journal of Sport and Health Science 2023年第1期12卷 45-51页

作者： Lei Li Jinye Liang Cong Zhang Tiemin Liu Chao Zhang Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Department of Biology University of IowaIowa CityIA 52242USA State Key Laboratory of Genetic Engineering Department of Endocrinology and Metabolismand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.

关键词： Body weight Energy homeostasis GPCR melanocortin-4 receptor

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melanocortin-4 receptor Expression in the Rostral Ventromedial Medulla Involved in Modulation of Nociception in Transgenic Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第2期33卷 195-198页

作者：潘旭初宋咏堂刘成项红兵卢传坚 Medical Association of Hubei Province Department of Anesthesiology and Pain Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Dermatology Guangdong Provincial Hospital of Traditional Chinese Medicine

The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor （MC4R） expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein （GFP） under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus （NRM） and nucleus gigantocellularis pars a （NGCa）]. Fluorescence immunohisto- chemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryp- tophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.

关键词： melanocortin-4 receptor nociception rostral ventromedial medulla

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Functional roles of melanocortin-4 receptor in hippocampal synapse

Functional roles of melanocortin-4 receptor in hippocampal s...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Amy K.Y.FU Nancy Y.IP Division of Life Science Molecular Neuroscience Center and State Key Laboratory of Molecular NeuroscienceThe Hong Kong University of Science and TechnologyClear Water Bay

＜正＞Objective melanocortin-4 receptor（MC4R）,which belongs to the G-protein coupled receptor（GPCR） superfamily,is one of the five melanocortin receptors（MCRs）that is expressed abundantly in the central nervous system.MC4R is activated by various endogenous ligands including melanocyte stimulating hormone（MSH）,and adrenocorticotropin hormones.The central melanocortin signaling in the hypothalamus-pituitary-adrenal axis system is critical for regulating various aspects of energy homeostasis and feeding behavior.Although MC4R is highly expressed in other brain regions such as cortex and hippocampus,the roles of MC4R in these regions remain elusive.In this study,the functional role of MC4R in synapse plasticity in hippocampus is examined.Methods The regulation of MC4R protein in hippocampal neurons was examined using immunocytochemical analysis and Western blot analysis.The function of MC4R in hippocampal neurons was studied by RNA interference using calcium phosphate transfection.Results（1）MC4R protein increases in rat hippocampus upon development and enriched at the synaptic compartment.（2）Knockdown of MC4R in cultured rat hippocampal neurons results in a regulation in the density of dendritic spines,the sites where excitatory synapses reside.（3）Stimulation of MC4R increases the cAMP level in hippocampal neurons.Conclusion MC4R regulates the synapse functions through modulating the morphology of dendritic spines.

关键词： melanocortin-4 receptor cyclic AMP dendritic spines

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