Avances en el estudio de la neurobiología de la depresión: Rol de la hormona concentradora de melanina

Pablo Torterolo; Cecilia Scorza; Jessika Urbanavicius; Andrea Devera; Luciana Benedetto; Claudia Pascovich; Patricia Lagos; Michael H. Chase; Jaime Monti

Authors

Pablo Torterolo Universidad de la República, Facultad de Medicina, Departamento de Fisiología. Profesor Agregado
Cecilia Scorza Instituto de Investigaciones Biológicas Clemente Estable, Departamento de Neurofarmacología Experimental. Investigadora Jefa
Jessika Urbanavicius Instituto de Investigaciones Biológicas Clemente Estable, Laboratorio de Biología Celular. Investigadora
Andrea Devera Universidad de la República, Facultad de Medicina, Departamento de Fisiología. Ex Asistente y Asistente de Neonatología
Luciana Benedetto Universidad de la República, Facultad de Medicina, Departamento de Fisiología. Asistente
Claudia Pascovich Universidad de la República, Facultad de Medicina, Departamento de Fisiología. Asistente
Patricia Lagos Universidad de la República, Facultad de Medicina, Departamento de Fisiología. Prof. Adjunto
Michael H. Chase WebSciences International and University of California Los Angeles (UCLA) School of Medicine, USA. Prof. Emérito de UCLA. Prof. Ad Honorem de la Facultad de Medicina, Universidad de la República
Jaime Monti Universidad de la República, Facultad de Medicina, Departamento de Farmacología y Terapéutica. Prof. Ex Director

Keywords:

NEUROBIOLOGY, DEPRESSION, MAJOR DEPRESSIVE DISORDER, MELANIN CONCENTRATING HORMONE

Abstract

Introduction: major depression disorder (MDD) is a common psychiatric condition, it has high morbility rates and is closely related to suicide.
Objective: to provide an update in the study of the neurobiology of depression, focusing on the potential role of the melanin-concentrating hormone (MCH) in this condition.
Method: a bibliographical review with an emphasis on our own original studies.
Results: the melanin-concentrating hormone is a peptide neuromodulator syhthetized by neurones in the hypothalamus. MCHergic neurons send projection towards different areas in the central nervous system, including areas associated to the regulation of the sleep-wake cycle, as well as different structures in the limbic system that take part in the regulation of mood. In spite of several studies having proved the MCHergic system with the control of energetic homeostasis, recent findings have enabled to identify a role for this system in the sleep generator mechanisms. Similarly, data arising from several studies suggests that MCH would be involved in the major depression disorder. Our own preclinical studies tend to pint out the MCH promotes the generation of REM sleep and a type of depression. Apparently both effects would be mediated through the modulation of the activity on the serotoninergic neurons in the dorsal raphe nucleus.
Conclusions: paraclinical studies suggest the leading role of the MCHergic system in the pathophysiology of depression. It is to be proved still, whether this affirmation is true for patients with major depression disorder.

References

(1) American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 4 ed. Washington (DC): APA, 1994.
(2) Montalbán A. El suicidio: la urgencia de un grave problema. Rev Méd Urug 2004; 20(2): 91.
(3) Lucero Abreu R. Suicidios en Uruguay: su relación con la economía nacional (1972-1992). Rev Méd Urug 1998; 14(3): 236-47.
(4) Saveanu RV, Nemeroff CB. Etiology of depression: genetic and environmental factors. Psychiatr Clin North Am 2012; 35(1):51-71.
(5) Willner P, Scheel-Krüger J, Belzung C. The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 2013; 37(10 Pt 1):2331-71.
(6) Palazidou E. The neurobiology of depression. Br Med Bull 2012; 101:127-45.
(7) Palagini L, Baglioni C, Ciapparelli A, Gemignani A, Riemann D. REM sleep dysregulation in depression: state of the art. Sleep Med Rev 2013; 17(5):377-90.
(8) Monti JM. The structure of the dorsal raphe nucleus and its relevance to the regulation of sleep and wakefulness. Sleep Med Rev 2010; 14(5):307-17.
(9) Bondy B, Buettner A, Zill P. Genetics of suicide. Mol Psychiatry 2006; 11(4):336-51.
(10) López-Rodríguez F, Kim J, Poland RE. Total sleep deprivation decreases immobility in the forced-swim test. Neuropsychopharmacology 2004; 29(6):1105-11.
(11) Torterolo P, Yamuy J, Sampogna S, Morales FR, Chase MH. GABAergic neurons of the cat dorsal raphe nucleus express c-fos during carbachol-induced active sleep. Brain Res 2000; 884(1-2):68-76.
(12) Macneil DJ. The role of melanin-concentrating hormone and its receptors in energy homeostasis. Front Endocrinol (Lausanne) 2013; 4:49.
(13) Torterolo P, Lagos P, Monti JM. Melanin-concentrating hormone: a new sleep factor? Front Neurol 2011; 2:14.
(14) Monti JM, Torterolo P, Lagos P. Melanin-concentrating hormone control of sleep-wake behavior. Sleep Med Rev 2013; 17(4):293-8.
(15) Torterolo P, Sampogna S, Morales FR, Chase MH. MCH-containing neurons in the hypothalamus of the cat: searching for a role in the control of sleep and wakefulness. Brain Res 2006; 1119(1):101-14.
(16) Torterolo P, Sampogna S, Chase MH. MCHergic projections to the nucleus pontis oralis participate in the control of active (REM) sleep. Brain Res 2009; 1268:76-87.
(17) Torterolo P, Rojas M, Sampogna S, Morales FR, Chase MH. MCH-containing neurons and the control of sleep and wakefulness. Sleep 2003; 26:A20.
(18) Torterolo P, Vanini G. Nuevos conceptos sobre la generación y el mantenimiento de la vigilia. Rev Neurol 2010; 50(12):747-58.
(19) Torterolo P, Vanini G. Importancia de las hipocretinas en al patogenia de la narcolepsia: breve revisión. Rev Méd Urug 2003; 19(1):27-33.
(20) Lagos P, Urbanavicius J, Scorza MC, Miraballes R, Torterolo P. Depressive-like profile induced by MCH microinjections into the dorsal raphe nucleus evaluated in the forced swim test. Behav Brain Res 2011; 218(2):259-66.
(21) Torterolo P, Lagos P, Sampogna S, Chase MH. Melanin-concentrating hormone (MCH) immunoreactivity in non-neuronal cells within the raphe nuclei and subventricular region of the brainstem of the cat. Brain Res 2008; 1210:163-78.
(22) Ungerfeld R, Alzugaray S, Quintela HG, Lagos P, Torterolo P, Bielli A. Melanin concentrating hormone (MCH) in the cerebrospinal fluid of ewes during spontaneous oestrous cycles and ram effect induced follicular phases. Peptides 2011; 32(12):2511-3.
(23) Calegare B, Fernandes L, Dias A, Costa A, Lagos P, Torterolo P, et al. Melanin-concentrating hormone levels in the CSF during paradoxical sleep deprivation and rebound: comparison with hypocretin-1 (orexin-A). En prensa 2013.
(24) Peyron C, Valentin F, Bayard S, Hanriot L, Bedetti C, Rousset B, et al. Melanin concentrating hormone in central hypersomnia. Sleep Med 2011; 12(8):768-72.
(25) Verret L, Goutagny R, Fort P, Cagnon L, Salvert D, Léger L, et al. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep. BMC Neurosci 2003; 4:19.
(26) Hassani OK, Lee MG, Jones BE. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci U S A 2009; 106(7):2418-22.
(27) Blouin AM, Fried I, Wilson CL, Staba RJ, Behnke EJ, Lam HA, et al. Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction. Nat Commun 2013; 4:1547.
(28) Ahnaou A, Drinkenburg WH, Bouwknecht JA, Alcazar J, Steckler T, Dautzenberg FM. Blocking melanin-concentrating hormone MCH1 receptor affects rat sleep-wake architecture. Eur J Pharmacol 2008; 579(1-3):177-88.
(29) Lagos P, Torterolo P, Jantos H, Chase MH, Monti JM. Effects on sleep of melanin-concentrating hormone (MCH) microinjections into the dorsal raphe nucleus. Brain Res 2009; 1265:103-10.
(30) Lagos P, Torterolo P, Jantos H, Monti JM. Immunoneutralization of melanin-concentrating hormone (MCH) in the dorsal raphe nucleus: effects on sleep and wakefulness. Brain Res 2011; 1369:112-8.
(31) Lagos P, Monti JM, Jantos H, Torterolo P. Microinjection of the melanin-concentrating hormone into the lateral basal forebrain increases REM sleep and reduces wakefulness in the rat. Life Sci 2012; 90(23-24):895-9.
(32) Benedetto L, Rodriguez-Servetti Z, Lagos P, D’Almeida V, Monti JM, Torterolo P. Microinjection of melanin concentrating hormone into the lateral preoptic area promotes non-REM sleep in the rat. Peptides 2013; 39:11-5.
(33) Konadhode RR, Pelluru D, Blanco-Centurion C, Zayachkivsky A, Liu M, Uhde T, et al. Optogenetic stimulation of MCH neurons increases sleep. J Neurosci 2013; 33(25):10257-63.
(34) Urbanavicius J, Lagos P, Torterolo P, Scorza C. Role of melanin concentrating hormone (MCH) on the dorsal raphe nucleus (DRN): its relevance for depression. J Neurochem 2013; 125: 265.
(35) Borowsky B, Durkin MM, Ogozalek K, Marzabadi MR, DeLeon J, Lagu B, et al. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med 2002; 8(8):825-30.
(36) Chung S, Parks GS, Lee C, Civelli O. Recent updates on the melanin-concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists. J Mol Neurosci 2011; 43(1):115-21.
(37) Shimazaki T, Yoshimizu T, Chaki S. Melanin-concentrating hormone MCH1 receptor antagonists: a potential new approach to the treatment of depression and anxiety disorders. CNS Drugs 2006; 20(10):801-11.
(38) García-Fuster MJ, Parks GS, Clinton SM, Watson SJ, Akil H, Civelli O. The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior. Eur Neuropsychopharmacol 2012; 22(8):607-13.
(39) López Hill X, Pascovich C, Urbanavicius J, Torterolo P, Scorza MC. The median raphe nucleus participates in the depressive-like behavior induced by MCH: differences with the dorsal raphe nucleus. Peptides 2013; 50:96-9.
(40) Kátai Z, Adori C, Kitka T, Vas S, Kalmár L, Kostyalik D, et al. Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation. Psychopharmacology (Berl) 2013; 228(3):439-49.
(41) Benedetto L, Pereira M, Ferreirra A, Torterolo P. Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior. Peptides 2014; 58:20-5.