Avances en el estudio de la neurobiología de la depresión
Rol de la hormona concentradora de melanina
Palabras clave:
NEUROBIOLOGÍA, DEPRESIÓN, TRASTORNO DEPRESIVO MAYOR, HORMONA CONCENTRADORA DE MELANINA
Resumen
Introducción: la depresión mayor (DM) es una enfermedad psiquiátrica frecuente, con importante morbilidad y una relación estrecha con el suicidio.
Objetivo: hacer una puesta a punto de los avances en el estudio de la neurobiología de la DM, enfocándonos en el posible rol de la hormona concentradora de melanina (MCH) en esta patología.
Metodología: revisión de la bibliografía con énfasis en nuestros propios trabajos originales.
Resultados: la MCH es un neuromodulador peptídico sintetizado por neuronas del hipotálamo. Las neuronas MCHérgicas envían proyecciones hacia diversas regiones del sistema nervioso central, incluyendo las áreas vinculadas con la regulación de la vigilia y del sueño, así como a diversas estructuras del sistema límbico que participan en la regulación del humor. Aunque numerosos estudios han relacionado el sistema MCHérgico con el control de la homeostasis energética, hallazgos recientes han permitido señalar un rol de este sistema en los mecanismos de generación del sueño. A su vez, una convergencia de datos provenientes de diversos estudios sugiere que la MCH estaría involucrada en la fisiopatología de la DM. Nuestros propios estudios preclínicos tienden a indicar que la MCH promueve la generación del sueño REM y un estado tipo depresivo. Ambos efectos estarían siendo mediados a través de la modulación de la actividad de las neuronas serotoninérgicas del núcleo dorsal del rafe.
Conclusiones: estudios preclínicos sugieren un rol protagónico del sistema MCHérgico en la fisiopatología de la depresión. Resta confirmar si esta afirmación es cierta en pacientes con DM.
Citas
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(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.
(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.
Publicado
2014-06-30
Cómo citar
1.
Torterolo P, Scorza C, Urbanavicius J, Devera A, Benedetto L, Pascovich C, Lagos P, Chase MH, Monti J. Avances en el estudio de la neurobiología de la depresión. Rev. Méd. Urug. [Internet]. 30 de junio de 2014 [citado 25 de noviembre de 2024];30(2):128-36. Disponible en: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/252
Sección
Trabajos de Revisión o Actualización y Puestas al día
