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Jean-louis Nahon - One of the best experts on this subject based on the ideXlab platform.

  • Melanin-Concentrating Hormone receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
    IUPHAR BPS Guide to Pharmacology CITE, 2019
    Co-Authors: Valerie Audinot, Jean-louis Nahon, Bernard Lakaye, Jean A. Boutin, Yumito Saito
    Abstract:

    Melanin-Concentrating Hormone (MCH) receptors (provisional nomenclature as recommended by NC-IUPHAR [31]) are activated by an endogenous nonadecameric cyclic peptide identical in humans and rats (DFDMLRCMLGRVYRPCWQV; mammalian MCH) generated from a precursor (PMCH, P20382), which also produces neuropeptide EI and neuropeptide GE.

  • The Melanin-Concentrating Hormone
    Handbook of Biologically Active Peptides, 2006
    Co-Authors: Jean-louis Nahon
    Abstract:

    ABSTRACT The Melanin-Concentrating Hormone (MCH) is a cyclic peptide highly conserved in vertebrates that was originally characterized as a neurohypophysial skin paling factor in teleosts. In fish, MCH may also participate in the control of the stress response. Mammalian MCH is a hypothalamic neuropeptide that displays multiple functions, mostly controlling feeding behavior and energy homeostasis and regulating the stress axis and emotion. The MCH precursor may generate additional putative peptides in the brain and peripheral organs but their roles remain poorly explored. In mammals, alternative splicing and antisense transcription at the MCH gene locus lead to production of novel proteins whereas variant MCH genes were found only in primates. Two G protein–coupled MCH receptors were found in fish and primates, while a single one appears functional in rodents. Transgenic mouse models and pharmacological studies have demonstrated the importance of the MCH signaling pathway as a potential target to treat appetite disorders, obesity, and also anxiety and depression.

  • Acute and chronic administration of Melanin-Concentrating Hormone enhances food intake and body weight in Wistar and Sprague-Dawley rats.
    International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 2002
    Co-Authors: O Della-zuana, Françoise Presse, Jean-louis Nahon, Christine Ortola, Jacques Duhault, Nigel Levens
    Abstract:

    Acute and chronic administration of Melanin-Concentrating Hormone enhances food intake and body weight in Wistar and Sprague–Dawley rats

  • Chapter II The Melanin-Concentrating Hormone
    Handbook of Chemical Neuroanatomy, 2002
    Co-Authors: Guillaume Hervieu, Françoise Presse, Laurence Maulon-feraille, Jonathan K. Chambers, Jane E. Cluderay, Shelagh Wilson, Jean-louis Nahon
    Abstract:

    Publisher Summary This chapter presents the most recent findings on structural analysis and neurobiology of Melanin-Concentrating Hormone (MCH), with special emphasis on the cloning, functional characterization and neuronal distribution of at least two MCH receptors. It was a long-standing and important achievement. MCH is classified as a melanotropin—that is, a factor implicated in regulating color tegument. However, unlike the MSH and adrenocorticotropic Hormone (ACTH) peptide family, all derived from the prepro-opio-melanocortin (POMC) precursor, MCH is not classified as a melanocortin because it lacks the consensus melanocortin sequence -His-Phe-Arg-Trp-. Consistent with that, MCH does not signal through the specific set of not less than six G-protein-coupled receptor (GPCR) proteins binding MSHs and ACTH, and termed from MC-1 to MC-6 binding. Intriguingly, it may be possible that MCH and MSH are evolutionary related.

  • Effects of Leptin on Melanin-Concentrating Hormone Expression in the Brain of Lean and Obese Lepob/Lepob Mice
    Neuroendocrinology, 1999
    Co-Authors: Qingling Huang, Jean-louis Nahon, Agnès Viale, Frédéric Picard, Denis Richard
    Abstract:

    The effect of leptin on the expression of Melanin-Concentrating Hormone (MCH) was investigated in lean and genetically obese Lepob/Lepob mice. Murine leptin was subcutaneously in

Qi Dai - One of the best experts on this subject based on the ideXlab platform.

  • Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating.
    The international journal of neuropsychopharmacology, 2020
    Co-Authors: P. Vawter, Anton Schulmann, Lamees Alhassen, Wedad Alhassen, Abdul Rezzak Hamzeh, Jasmine Sakr, Lucas Pauluk, Ryan F. Yoshimura, Xuejie Wang, Qi Dai
    Abstract:

    Author(s): Vawter, Marquis P; Schulmann, Anton; Alhassen, Lamees; Alhassen, Wedad; Hamzeh, Abdul Rezzak; Sakr, Jasmine; Pauluk, Lucas; Yoshimura, Ryan; Wang, Xuejie; Dai, Qi; Sanathara, Nayna; Civelli, Olivier; Alachkar, Amal | Abstract: BACKGROUND:Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide Melanin Concentrating Hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the Melanin Concentrating Hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association. METHODS:We analyzed MCHR1 and pro-Melanin Concentrating Hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the Melanin Concentrating Hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of Melanin Concentrating Hormone expressing neurons using a Cre-inducible diphtheria toxin system. RESULTS:MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P l .05, CommonMind and PsychEncode combined datasets, n = 901) while pro-Melanin Concentrating Hormone is below the detection threshold. MCHR1 expression decreased with aging (P = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of pro-Melanin Concentrating Hormone neurons increased repetitive behavior and produced a deficit in sensorimotor gating. CONCLUSIONS:Our study indicates that early disruption of the Melanin Concentrating Hormone system interferes with neurodevelopmental processes, which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by Melanin Concentrating Hormone may lead to a therapeutic target for early prevention of schizophrenia.

  • Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating.
    eScholarship University of California, 2020
    Co-Authors: Vawter, Marquis P, Schulmann Anton, Alhassen Lamees, Alhassen Wedad, Hamzeh, Abdul Rezzak, Sakr Jasmine, Pauluk Lucas, Yoshimura Ryan, Wang Xuejie, Qi Dai
    Abstract:

    BACKGROUND:Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide Melanin Concentrating Hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the Melanin Concentrating Hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association. METHODS:We analyzed MCHR1 and pro-Melanin Concentrating Hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the Melanin Concentrating Hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of Melanin Concentrating Hormone expressing neurons using a Cre-inducible diphtheria toxin system. RESULTS:MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P < .05, CommonMind and PsychEncode combined datasets, n = 901) while pro-Melanin Concentrating Hormone is below the detection threshold. MCHR1 expression decreased with aging (P = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of pro-Melanin Concentrating Hormone neurons increased repetitive behavior and produced a deficit in sensorimotor gating. CONCLUSIONS:Our study indicates that early disruption of the Melanin Concentrating Hormone system interferes with neurodevelopmental processes, which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by Melanin Concentrating Hormone may lead to a therapeutic target for early prevention of schizophrenia

Anthony P. Weetman - One of the best experts on this subject based on the ideXlab platform.

  • Melanin-Concentrating Hormone and Melanin-Concentrating Hormone receptors in mammalian skin physiopathology
    Peptides, 2009
    Co-Authors: E. Helen Kemp, Anthony P. Weetman
    Abstract:

    To date, there is a dearth of evidence to support functions for Melanin-Concentrating Hormone (MCH) and Melanin-Concentrating Hormone receptors (MCH-R) in mammalian skin physiology including pigmentation, inflammation and immune responses and skin cell proliferation. Much research is therefore still needed to define the roles of the Hormone and its receptors in mammalian skin. This will be a crucial step to identifying pathogenic mechanisms that may involve the MCH/MCH-R system in the context of inflammatory and autoimmune skin diseases as well as skin cancers. The following review summarizes the studies which have been carried out to examine the expression and function of MCH and MCH-R in mammalian skin. Recent findings with regard to humoral immune responses to the MCH-R1 in patients with the skin depigmenting disease vitiligo are also discussed.

  • Function-blocking autoantibodies to the Melanin-Concentrating Hormone receptor in vitiligo patients
    Laboratory Investigation, 2006
    Co-Authors: Raju V.s.r.k. Gottumukkala, Anthony P. Weetman, Philip F. Watson, David J. Gawkrodger, Nikos G Gavalas, Samia Akhtar, Russell A Metcalfe, John W Haycock, Elizabeth Helen Kemp
    Abstract:

    Vitiligo is a common depigmenting skin disorder resulting from the loss of melanocytes in the cutaneous epidermis. Although the cause of the disease remains obscure, autoimmune mechanisms are thought to be involved. Recently, Melanin-Concentrating Hormone receptor (MCHR)-binding autoantibodies have been identified in vitiligo patients. In the present study, we aimed to determine if MCHR autoantibodies could also affect receptor function either by direct activation or by blocking its response to Melanin-Concentrating Hormone. The results indicated that 10/18 (56%) vitiligo patient IgG samples inhibited the function of MCHR expressed in a Chinese hamster ovary cell line. In contrast, neither control ( n =20) nor SLE patient ( n =10) IgG samples blocked receptor function. Compared with healthy controls, MCHR function-blocking autoantibodies were found at a significantly increased frequency in the vitiligo patient group ( P =0.0004). No MCHR-activating autoantibodies were detected in any of the vitiligo patient, SLE patient or control IgG samples that were analysed. In addition, vitiligo patient IgGs were tested for MCHR autoantibodies that could mediate antibody-dependent cell-mediated cytotoxicity via the receptor. However, this could only be demonstrated in two vitiligo patient sera. Overall, this work has provided additional evidence that MCHR is a B-cell autoantigen in vitiligo and has demonstrated the existence of MCHR function-blocking autoantibodies further to the receptor-binding autoantibodies previously reported.

  • Autoantibodies in Vitiligo Patients Recognize Multiple Domains of the Melanin-Concentrating Hormone Receptor
    The Journal of investigative dermatology, 2003
    Co-Authors: Raju V.s.r.k. Gottumukkala, E. Helen Kemp, Anthony P. Weetman, E A Waterman, Laura M. Herd, Philip F. Watson, David J. Gawkrodger
    Abstract:

    Previously, we reported the identification of autoantibodies against the Melanin-Concentrating Hormone receptor 1 in patients with vitiligo. In this study, the B cell epitopes on Melanin-Concentrating Hormone receptor 1 that are recognized by these autoantibodies have been identified. Deletion derivatives of Melanin-Concentrating Hormone receptor 1 complementary DNA were constructed and then translated in vitro with the concomitant incorporation of [35S]-methionine into the protein products. The [35S]-labeled Melanin-Concentrating Hormone receptor 1 derivatives were subsequently used in radio-binding assays to investigate the reactivity of sera from nine vitiligo patients that were known to contain antibodies to the receptor. Analysis of the results obtained in the radio-binding assays suggested the existence of multiple antibody binding sites on Melanin-Concentrating Hormone receptor 1, including regions between amino acids 1 to 138 and 139 to 298. Several patients exhibited autoantibodies to more than one Melanin-Concentrating Hormone receptor 1 epitope indicating a heterogeneous humoral response to the receptor. Computer prediction of the potential B cell epitopes on Melanin-Concentrating Hormone receptor 1 revealed that the epitope domains identified overlapped, at least in part, with regions predicted to be highly antigenic.

Jackson C. Bittencourt - One of the best experts on this subject based on the ideXlab platform.

  • Melanin-Concentrating Hormone and sleep.
    Current opinion in neurobiology, 2017
    Co-Authors: Jozélia G. Ferreira, Jackson C. Bittencourt, Antoine Roger Adamantidis
    Abstract:

    The Melanin-Concentrating Hormone (MCH) is an essential neuromodulator involved with homeostatic regulation and motivated behaviors. The majority of MCH neurons are localized within the zona incerta, lateral hypothalamic and incerto-hypothalamic areas but others regions, as the olfactory turbecle, the laterodorsal tegmental nucleus, the paramediam pontine reticular formation and the medial preoptic area, can also express the peptide depending on the gender and metabolic state of the animal. If the MCH on these novel sites of expression are also related with the control of wake-sleep cycle will be discuss in this review.

  • Hypothalamic Melanin-Concentrating Hormone projections to the septo-hippocampal complex in the rat
    Journal of chemical neuroanatomy, 2012
    Co-Authors: Fernando Fusari Bento De Lima, Luciane V. Sita, Amanda Ribeiro De Oliveira, Helder C. Costa, Joelcimar M. Da Silva, Renato A. Mortara, Carlos Alexandre Dos Santos Haemmerle, Gilberto Fernando Xavier, Newton S. Canteras, Jackson C. Bittencourt
    Abstract:

    Melanin-Concentrating Hormone (MCH) and neuropeptide glutamic acid-isoleucine (NEI) are expressed in neurons that are located mainly in the hypothalamus and project widely throughout the rat central nervous system. One of the main targets of Melanin-Concentrating Hormone is the hippocampal formation, although the exact origin of the projections is unknown. By using injections of the retrograde tracer True Blue into the hippocampus, together with immunohistochemical analysis, we observed retrogradely labeled Melanin-Concentrating Hormone-containing neurons in the lateral hypothalamic area, incerto-hypothalamic area, perifornical area, the periventricular nucleus of the hypothalamus, and in the internuclear area (between the dorsomedial and ventromedial nuclei of the hypothalamus), as well as a few retrogradely labeled and Melanin-Concentrating Hormone-immunoreactive cells in the supramammillary nucleus. The afferents from the lateral hypothalamic area were confirmed using injection of the anterograde tracer biotinylated dextran amine, which enabled us to use histochemical analysis in order to visualize fibers and terminals in the hippocampal formation. In the medial septal nucleus, we found cholinergic neurons that are also putatively innervated by Melanin-Concentrating Hormone immunoreactive fibers and project to the hippocampal formation. Finally, using two different protocols for immunoperoxidase, we were able to show GABAergic basket cells presumably innervated by Melanin-Concentrating Hormone-immunoreactive fibers in the hippocampal formation. On the basis of the data collected herein, we hypothesize that the MCH/NEI projections from hypothalamic nuclei participate in spatial memory and learning through direct and indirect pathways. These pathways would enable the animal to organize its exploratory behavior during foraging.

  • Distribution of Melanin-Concentrating Hormone neurons projecting to the medial mammillary nucleus
    Neuroscience, 2002
    Co-Authors: Cláudio Aparecido Casatti, Carol Fuzetti Elias, Luciane V. Sita, V C G. Furlani, J. A. Bauer, Lucio Frigo, Jackson C. Bittencourt
    Abstract:

    Abstract The Melanin-Concentrating Hormone and neuropeptide glutamic acid-isoleucine are expressed in neurons located mainly in the hypothalamus that project widely throughout the CNS. One of the Melanin-Concentrating Hormone main targets is the medial mammillary nucleus, but the exact origin of these fibers is unknown. We observed Melanin-Concentrating Hormone and neuropeptide glutamic acid-isoleucine immunoreactive fibers coursing throughout the mammillary complex, showing higher density in the pars lateralis of the medial mammillary nucleus, while the lateral mammillary nucleus showed sparse Melanin-Concentrating Hormone innervation. The origins of these afferents were determined by using implant of the retrograde tracer True Blue in the medial mammillary nucleus. Double-labeled neurons were observed in the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus. A considerable population of retrogradely labeled Melanin-Concentrating Hormone perikaryal profiles was also immunoreactive to neuropeptide glutamic acid-isoleucine (74±15% to 85±15%). The afferents from the lateral hypothalamic area, rostromedial zona incerta and dorsal tuberomammillary nucleus to the medial mammillary nucleus were confirmed using implant of the anterograde tracer Phaseolus vulgaris leucoagglutinin. In addition, using double-labeled immunohistochemistry, we found no co-localization between neurons expressing Melanin-Concentrating Hormone and adenosine deaminase (histaminergic marker) in the dorsal tuberomammillary nucleus. We hypothesize that these Melanin-Concentrating Hormone projections participate in spatial memory process mediated by the medial mammillary nucleus. These pathways would enable the animal to look for food during the initial moments of appetite stimulation.

  • The distribution of Melanin-Concentrating Hormone in the monkey brain (Cebus apella)
    Brain research, 1998
    Co-Authors: Jackson C. Bittencourt, Cláudio Aparecido Casatti, Lucio Frigo, Jean-louis Nahon, Robert A. Rissman, J. A. Bauer
    Abstract:

    Melanin-Concentrating Hormone was identified in the brain of Cebus monkey using immunohistochemical and in situ hybridization. MCH-immunoreactive neurons were found in the lateral hypothalamus and dorsolateral zona incerta. MCH-ir fibers were seen in the medial mammillary nucleus, and in the median eminence, and very few fibers in the globus pallidus. This is the first report describing the MCH-ir cell and fiber distribution in the monkey brain.

Ashley M Blouin - One of the best experts on this subject based on the ideXlab platform.

  • human hypocretin and Melanin Concentrating Hormone levels are linked to emotion and social interaction
    Nature Communications, 2013
    Co-Authors: Ashley M Blouin, Itzhak Fried, Charles L Wilson, Richard J Staba, Eric Behnke, Nigel T Maidment, Karl Ae Karlsson, Jennifer L Lapierre
    Abstract:

    The emotional state of humans depends on the temporal concentration of neurochemicals. Blouin et al. measure temporal changes in two neuropeptides, hypocretin and Melanin-Concentrating Hormone, and find that hypocretin but not Melanin-Concentrating Hormone is linked to positive emotions and social interaction.

  • Human hypocretin and Melanin-Concentrating Hormone levels are linked to emotion and social interaction
    Nature communications, 2013
    Co-Authors: Ashley M Blouin, Itzhak Fried, Charles L Wilson, Richard J Staba, Eric Behnke, Nigel T Maidment, Karl Ae Karlsson, Jennifer L Lapierre, Hoa A. Lam, Jerome M. Siegel
    Abstract:

    The neurochemical changes underlying human emotions and social behaviour are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and Melanin-Concentrating Hormone, measured in the human amygdala. We show that hypocretin-1 levels are maximal during positive emotion, social interaction and anger, behaviours that induce cataplexy in human narcoleptics. In contrast, Melanin-Concentrating Hormone levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. Melanin-Concentrating Hormone levels increase at sleep onset, consistent with a role in sleep induction, whereas hypocretin-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.