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A Commentary on the Therapeutic Potential of Melatonin and Its Analogues in CNS Conditions

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Psychiatry and Neuroscience Update

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Abstract

The hormone, melatonin, is secreted by the pineal gland in the mammalian brain. It plays an important role in the regulation of the circadian rhythm and the sleep-wake cycle. Now, melatonin is also recognized for its anti-oxidative and free radical scavenging functions, as well as being an important modulator of the anti-inflammatory response within the immune-pineal axis. Melatonin therefore can exert extensive influence over a wide range of psychophysiological functions – primarily through the activation of melatonin receptors: MT1 and MT2. Here, we briefly summarize the potential clinical applications of melatonin and its analogues and the suggestion that dysregulation of melatonin signalling in the brain constitutes as causal risk factor to neurodegenerative diseases and mood disorders. Clinical and preclinical evidence for the antidepression and antianxiety efficacy of melatonin and its synthetic analogues (e.g. agomelatine) is outlined. Mechanistically, the positive impact of melatonin on adult neurogenesis in the hippocampus has been linked to the observed mood-stabilizing effects of melatonin and its analogues according to the “neurogenic hypothesis” of antidepressant drug action. This together with the anti-inflammatory and anti-oxidative profile of melatonin may explain its unique therapeutic profile. Although there remain inconsistencies to be resolved, melatonin and its receptors are viable targets for the development of novel mood-stabilizing agents with fewer side effects. They could be viable alternatives for patients who cannot tolerate current antidepressant drugs as well as those who are not responding to current medication.

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References

  1. Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone PM, Rodriguez IR, Bégay V, Falcón J, Cahill GM, Cassone VM, Baler R. The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res. 1997;52:307–57.

    CAS  PubMed  Google Scholar 

  2. Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 2010;62(3):343–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Prendergast BJ. MT1 melatonin receptors mediate somatic, behavioral, and reproductive neuroendocrine responses to photoperiod and melatonin in Siberian hamsters (Phodopus sungorus). Endocrinology. 2010;151(2):714–21.

    Article  CAS  PubMed  Google Scholar 

  4. Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP, Dubocovich ML, Krause DN. MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther. 2002;302(3):1295–302.

    Article  CAS  PubMed  Google Scholar 

  5. Guerrero JM, Reiter RJ. Melatonin-immune system relationships. Curr Top Med Chem. 2002;2(2):167–79.

    Article  CAS  PubMed  Google Scholar 

  6. Jockers R, Maurice P, Boutin JA, Delagrange P. Melatonin receptors, heterodimerization, signal transduction and binding sites: what’s new? Br J Pharmacol. 2008;154(6):1182–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lacoste B, Angeloni D, Dominguez-Lopez S, Calderoni S, Mauro A, Fraschini F, Descarries L, Gobbi G. Anatomical and cellular localization of melatonin MT1 and MT2 receptors in the adult rat brain. J Pineal Res. 2015;58(4):397–417.

    Article  CAS  PubMed  Google Scholar 

  8. Ng KY, Leong MK, Liang H, Paxinos G. Melatonin receptors: distribution in mammalian brain and their respective putative functions. Brain Struct Funct. 2017; https://doi.org/10.1007/s00429-017-1439-6. [Epub ahead of print].

    Article  CAS  PubMed  Google Scholar 

  9. Sallinen P, Saarela S, Ilves M, Vakkuri O, Leppäluoto J. The expression of MT1 and MT2 melatonin receptor mRNA in several rat tissues. Life Sci. 2005;76(10):1123–34.

    Article  CAS  PubMed  Google Scholar 

  10. Petit L, Lacroix I, de Coppet P, Strosberg AD, Jockers R. Differential signaling of human Mel1a and Mel1b melatonin receptors through the cyclic guanosine 3′–5′-monophosphate pathway. Biochem Pharmacol. 1999;58(4):633–9.

    Article  CAS  PubMed  Google Scholar 

  11. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A. 1995;92(19):8734–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hunt AE, Al-Ghoul WM, Gillette MU, Dubocovich ML. Activation of MT(2) melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. Am J Physiol Cell Physiol. 2001;280(1):C110–8.

    Article  CAS  PubMed  Google Scholar 

  13. Cardinali DP, Pévet P. Basic aspects of melatonin action. Sleep Med Rev. 1998;2(3):175–90.

    Article  CAS  PubMed  Google Scholar 

  14. Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9(1):11–24.

    Article  PubMed  Google Scholar 

  15. Lavie P. Sleep-wake as a biological rhythm. Annu Rev Psychol. 2001;52:277–303.

    Article  CAS  PubMed  Google Scholar 

  16. Dawson D, Armstrong SM. Chronobiotics – drugs that shift rhythms. Pharmacol Ther. 1996;69(1):15–36.

    Article  CAS  PubMed  Google Scholar 

  17. Reiter RJ, Tan DX, Manchester LC, Lopez-Burillo S, Sainz RM, Mayo JC. Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. Adv Exp Med Biol. 2003;527:539–48.

    Article  CAS  PubMed  Google Scholar 

  18. Tomás-Zapico C, Coto-Montes A. A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J Pineal Res. 2005;39(2):99–104.

    Article  PubMed  CAS  Google Scholar 

  19. Poeggeler B. Melatonin, aging, and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine. 2005;27(2):201–12.

    Article  CAS  PubMed  Google Scholar 

  20. Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95.

    Article  CAS  PubMed  Google Scholar 

  21. Wickens AP. Ageing and the free radical theory. Respir Physiol. 2001;128(3):379–91.

    Article  CAS  PubMed  Google Scholar 

  22. Armstrong SM, Redman JR. Melatonin: a chronobiotic with anti-aging properties? Med Hypotheses. 1991;34(4):300–9.

    Article  CAS  PubMed  Google Scholar 

  23. Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra M, Hardeland R. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. 2002;2(2):181–97.

    Article  CAS  PubMed  Google Scholar 

  24. Reiter RJ, Tan DX, Cabrera J, D’Arpa D, Sainz RM, Mayo JC, Ramos S. The oxidant/antioxidant network: role of melatonin. Biol Signals Recept. 1999;8(1–2):56–63.

    Article  CAS  PubMed  Google Scholar 

  25. Hardeland R. Melatonin’s antioxidant properties: molecular mechanisms. In: Venkataramanujam S, Brzezinski A, Oter S, Shillcutt SD, editors. Melatonin and melatonergic drugs in clinical practice. Berlin: Springer; 2014. p. 17–26.

    Chapter  Google Scholar 

  26. Tan DX, Manchester LC, Reiter RJ, Plummer BF, Limson J, Weintraub ST, Qi W. Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation. Free Radic Biol Med. 2000;29(11):1177–85.

    Article  CAS  PubMed  Google Scholar 

  27. Blanchard B, Pompon D, Ducrocq C. Nitrosation of melatonin by nitric oxide and peroxynitrite. J Pineal Res. 2000;29(3):184–92.

    Article  CAS  PubMed  Google Scholar 

  28. Mahal HS, Sharma HS, Mukherjee T. Antioxidant properties of melatonin: a pulse radiolysis study. Free Radic Biol Med. 1999;26(5–6):557–65.

    Article  CAS  PubMed  Google Scholar 

  29. Kilańczyk E, Bryszewska M. The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. Cell Mol Biol Lett. 2003;8(2):333–6.

    PubMed  Google Scholar 

  30. Bruck R, Aeed H, Avni Y, Shirin H, Matas Z, Shahmurov M, Avinoach I, Zozulya G, Weizman N, Hochman A. Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats. J Hepatol. 2004;40(1):86–93.

    Article  CAS  PubMed  Google Scholar 

  31. Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabó C. Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res. 1997;23(2):106–16.

    Article  CAS  PubMed  Google Scholar 

  32. Li JH, Yu JP, Yu HG, Xu XM, Yu LL, Liu J, Luo HS. Melatonin reduces inflammatory injury through inhibiting NF-kappaB activation in rats with colitis. Mediat Inflamm. 2005;2005(4):185–93.

    Article  CAS  Google Scholar 

  33. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci. 2000;917:376–86.

    Article  CAS  PubMed  Google Scholar 

  34. Di Stefano A, Paulesu L. Inhibitory effect of melatonin on production of IFN gamma or TNF alpha in peripheral blood mononuclear cells of some blood donors. J Pineal Res. 1994;17(4):164–9.

    Article  PubMed  Google Scholar 

  35. Li B, Zhang H, Akbar M, Kim HY. Negative regulation of cytosolic phospholipase A(2) by melatonin in the rat pineal gland. Biochem J. 2000;351(Pt 3):709–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Radogna F, Diederich M, Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol. 2010;80(12):1844–52.

    Article  CAS  PubMed  Google Scholar 

  37. Carrillo-Vico A, Calvo JR, Abreu P, Lardone PJ, García-Mauriño S, Reiter RJ, Guerrero JM. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 2004;18(3):537–9.

    Article  CAS  PubMed  Google Scholar 

  38. Carrillo-Vico A, Lardone PJ, Fernández-Santos JM, Martín-Lacave I, Calvo JR, Karasek M, Guerrero JM. Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J Clin Endocrinol Metab. 2005;90(2):992–1000.

    Article  CAS  PubMed  Google Scholar 

  39. Lissoni P. Efficacy of melatonin in the immunotherapy of cancer using interleukin-2. In: Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke D, editors. The pineal gland and cancer: neuroimmunoendocrine mechanisms in malignancy. Berlin: Springer; 2001. p. 465–75.

    Chapter  Google Scholar 

  40. Yu Q, Miller SC, Osmond DG. Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow. J Pineal Res. 2000;29(2):86–93.

    Article  PubMed  Google Scholar 

  41. Sainz RM, Mayo JC, Uría H, Kotler M, Antolín I, Rodriguez C, Menendez-Pelaez A. The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J Pineal Res. 1995;19(4):178–88.

    Article  CAS  PubMed  Google Scholar 

  42. Cagnoli CM, Atabay C, Kharlamova E, Manev H. Melatonin protects neurons from singlet oxygen-induced apoptosis. J Pineal Res. 1995;18(4):222–6.

    Article  CAS  PubMed  Google Scholar 

  43. Iacovitti L, Stull ND, Johnston K. Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress. Brain Res. 1997;768(1–2):317–26.

    Article  CAS  PubMed  Google Scholar 

  44. Mizuno Y, Mochizuki H, Sugita Y, Goto K. Apoptosis in neurodegenerative disorders. Intern Med. 1998;37(2):192–3.

    Article  CAS  PubMed  Google Scholar 

  45. Ozsoy O, Yildirim FB, Ogut E, Kaya Y, Tanriover G, Parlak H, Agar A, Aslan M. Melatonin is protective against 6-hydroxydopamine-induced oxidative stress in a hemiparkinsonian rat model. Free Radic Res. 2015;49(8):1004–14.

    Article  CAS  PubMed  Google Scholar 

  46. Mayo JC, Sainz RM, Tan DX, Antolín I, Rodríguez C, Reiter RJ. Melatonin and Parkinson’s disease. Endocrine. 2005;27(2):169–78.

    Article  CAS  PubMed  Google Scholar 

  47. Esposito E, Cuzzocrea S. Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol. 2010;8(3):228–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK. Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci. 1997;17(5):1683–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Matsubara E, Bryant-Thomas T, Pacheco Quinto J, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leone A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E. Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J Neurochem. 2003;85(5):1101–8.

    Article  CAS  PubMed  Google Scholar 

  50. Feng Z, Chang Y, Cheng Y, Zhang BL, Qu ZW, Qin C, Zhang JT. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer’s disease. J Pineal Res. 2004;37(2):129–36.

    Article  CAS  PubMed  Google Scholar 

  51. Feng Z, Zhang JT. Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism. Free Radic Biol Med. 2004;37(11):1790–801.

    Article  CAS  PubMed  Google Scholar 

  52. Feng Z, Qin C, Chang Y, Zhang JT. Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer’s disease. Free Radic Biol Med. 2006;40(1):101–9.

    Article  CAS  PubMed  Google Scholar 

  53. He H, Dong W, Huang F. Anti-amyloidogenic and anti-apoptotic role of melatonin in Alzheimer disease. Curr Neuropharmacol. 2010;8(3):211–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fujimoto T, Nakamura T, Ikeda T, Takagi K. Potent protective effects of melatonin on experimental spinal cord injury. Spine (Phila Pa 1976). 2000;25(7):769–75.

    Article  CAS  Google Scholar 

  55. Pei Z, Cheung RT. Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model. J Pineal Res. 2004;37(2):85–91.

    Article  PubMed  CAS  Google Scholar 

  56. Pei Z, Pang SF, Cheung RT. Pretreatment with melatonin reduces volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model. J Pineal Res. 2002;32(3):168–72.

    Article  CAS  PubMed  Google Scholar 

  57. Oxenkrug GF, Bachurin SO, Prakhie IV, Zefirov NS. Quinone reductase 2 and antidepressant effect of melatonin derivatives. Ann N Y Acad Sci. 2010;1199:121–4.

    Article  CAS  PubMed  Google Scholar 

  58. Mahmood D, Muhammad BY, Alghani M, Anwar J, el-Lebban N, Haider M. Advancing role of melatonin in the treatment of neuropsychiatric disorders. Egypt J Basic Appl Sci. 2016;3:203–18.

    Google Scholar 

  59. Haridas S, Kumar M, Manda K. Melatonin ameliorates chronic mild stress induced behavioral dysfunctions in mice. Physiol Behav. 2013;119:201–7.

    Article  CAS  PubMed  Google Scholar 

  60. Lôo H, Hale A, D’haenen H. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol. 2002;17(5):239–47.

    Article  PubMed  Google Scholar 

  61. Fornaro M, McCarthy MJ, De Berardis D, De Pasquale C, Tabaton M, Martino M, Colicchio S, Cattaneo CI, D’Angelo E, Fornaro P. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study. Neuropsychiatr Dis Treat. 2013;9:243–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Montgomery SA. Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist. Eur Neuropsychopharmacol. 2006;16(Supplement 5):S633–8.

    Article  CAS  Google Scholar 

  63. Olié JP, Kasper S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol. 2007;10(5):661–73.

    PubMed  Google Scholar 

  64. Di Giannantonio M, Di Iorio G, Guglielmo R, De Berardis D, Conti CM, Acciavatti T, Cornelio M, Martinotti G. Major depressive disorder, anhedonia and agomelatine: an open-label study. J Biol Regul Homeost Agents. 2011;25(1):109–14.

    PubMed  Google Scholar 

  65. Taylor D, Sparshatt A, Varma S, Olofinjana O. Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies. BMJ. 2014;348:g1888.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Guaiana G, Gupta S, Chiodo D, Davies SJ, Haederle K, Koesters M. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev. 2013;12:CD008851.

    Google Scholar 

  67. Kennedy SH, Rizvi S, Fulton K, Rasmussen J. A double-blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR. J Clin Psychopharmacol. 2008;28(3):329–33.

    Article  CAS  PubMed  Google Scholar 

  68. Buoli M, Grassi S, Serati M, Altamura AC. Agomelatine for the treatment of generalized anxiety disorder. Expert Opin Pharmacother. 2017;18(13):1373–9.

    Article  CAS  PubMed  Google Scholar 

  69. deVries MW, Peeters FP. Melatonin as a therapeutic agent in the treatment of sleep disturbance in depression. J Nerv Ment Dis. 1997;185(3):201–2.

    Article  CAS  PubMed  Google Scholar 

  70. Johnson MW, Suess PE, Griffiths RR. Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006;63(10):1149–57.

    Article  CAS  PubMed  Google Scholar 

  71. Roth T, Stubbs C, Walsh JK. Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep. 2005;28(3):303–7.

    PubMed  Google Scholar 

  72. Hansen MV, Andersen LT, Madsen MT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat. 2014;145(3):683–95.

    Article  CAS  PubMed  Google Scholar 

  73. Samarkandi A, Naguib M, Riad W, Thalaj A, Alotibi W, Aldammas F, Albassam A. Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study. Eur J Anaesthesiol. 2005;22(3):189–96.

    Article  CAS  PubMed  Google Scholar 

  74. Khezri MB, Merate H. The effects of melatonin on anxiety and pain scores of patients, intraocular pressure, and operating conditions during cataract surgery under topical anesthesia. Indian J Ophthalmol. 2013;61(7):319–24.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Hansen MV, Halladin NL, Rosenberg J, Gögenur I, Møller AM. Melatonin for pre- and postoperative anxiety in adults. Cochrane Database Syst Rev. 2015;4:CD009861.

    Google Scholar 

  76. Patel T, Kurdi MS. A comparative study between oral melatonin and oral midazolam on preoperative anxiety, cognitive, and psychomotor functions. J Anaesthesiol Clin Pharmacol. 2015;31(1):37–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kain ZN, MacLaren JE, Herrmann L, Mayes L, Rosenbaum A, Hata J, Lerman J. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology. 2009;111(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  78. Loiseau F, Le Bihan C, Hamon M, Thiébot MH. Effects of melatonin and agomelatine in anxiety-related procedures in rats: interaction with diazepam. Eur Neuropsychopharmacol. 2006;16(6):417–28.

    Article  CAS  PubMed  Google Scholar 

  79. Kumar A, Kaur G, Rinwa P. Buspirone along with melatonin attenuates oxidative damage and anxiety-like behavior in a mouse model of immobilization stress. Chin J Nat Med. 2014;12(8):582–9.

    CAS  PubMed  Google Scholar 

  80. Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry. 1998;155(8):1119–21.

    Article  CAS  PubMed  Google Scholar 

  81. Williams WP 3rd, McLin DE 3rd, Dressman MA, Neubauer DN. Comparative review of approved melatonin agonists for the treatment of circadian rhythm sleep-wake disorders. Pharmacotherapy. 2016;36(9):1028–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Serfaty MA, Osborne D, Buszewicz MJ, Blizard R, Raven PW. A randomized double-blind placebo-controlled trial of treatment as usual plus exogenous slow-release melatonin (6 mg) or placebo for sleep disturbance and depressed mood. Int Clin Psychopharmacol. 2010;25(3):132–42.

    Article  PubMed  Google Scholar 

  83. Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000;20(24):9104–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. DeCarolis NA, Eisch AJ. Hippocampal neurogenesis as a target for the treatment of mental illness: a critical evaluation. Neuropharmacology. 2010;58(6):884–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ruan L, Lau BW, Wang J, Huang L, Zhuge Q, Wang B, Jin K, So KF. Neurogenesis in neurological and psychiatric diseases and brain injury: from bench to bedside. Prog Neurobiol. 2014;115:116–37.

    Article  PubMed  Google Scholar 

  86. Banasr M, Duman RS. Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets. 2007;6(5):311–20.

    Article  CAS  PubMed  Google Scholar 

  87. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301(5634):805–9.

    Article  CAS  PubMed  Google Scholar 

  88. Airan RD, Meltzer LA, Roy M, Gong Y, Chen H, Deisseroth K. High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science. 2007;317(5839):819–23.

    Article  CAS  PubMed  Google Scholar 

  89. David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, Drew M, Craig DA, Guiard BP, Guilloux JP, Artymyshyn RP, Gardier AM, Gerald C, Antonijevic IA, Leonardo ED, Hen R. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron. 2009;62(4):479–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, Zhang X. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005;115(11):3104–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Valente MM, Bortolotto V, Cuccurazzu B, Ubezio F, Meneghini V, Francese MT, Canonico PL, Grilli M. α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress. Mol Pharmacol. 2012;82(2):271–80.

    Article  CAS  PubMed  Google Scholar 

  92. Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, Arango V. Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology. 2009;34(11):2376–89.

    Article  CAS  PubMed  Google Scholar 

  93. Kim MJ, Kim HK, Kim BS, Yim SV. Melatonin increases cell proliferation in the dentate gyrus of maternally separated rats. J Pineal Res. 2004;37(3):193–7.

    Article  CAS  PubMed  Google Scholar 

  94. Rennie K, De Butte M, Pappas BA. Melatonin promotes neurogenesis in dentate gyrus in the pinealectomized rat. J Pineal Res. 2009;47(4):313–7.

    Article  CAS  PubMed  Google Scholar 

  95. Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Spina E, Cuzzocrea S. Melatonin’s stimulatory effect on adult hippocampal neurogenesis in mice persists after ovariectomy. J Pineal Res. 2011;51(3):353–60.

    Article  CAS  PubMed  Google Scholar 

  96. Sotthibundhu A, Phansuwan-Pujito P, Govitrapong P. Melatonin increases proliferation of cultured neural stem cells obtained from adult mouse subventricular zone. J Pineal Res. 2010;49(3):291–300.

    Article  CAS  PubMed  Google Scholar 

  97. Kong X, Li X, Cai Z, Yang N, Liu Y, Shu J, Pan L, Zuo P. Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cell Mol Neurobiol. 2008;28(4):569–79.

    Article  CAS  PubMed  Google Scholar 

  98. Kilic E, Kilic U, Bacigaluppi M, Guo Z, Abdallah NB, Wolfer DP, Reiter RJ, Hermann DM, Bassetti CL. Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice. J Pineal Res. 2008;45(2):142–8.

    Article  CAS  PubMed  Google Scholar 

  99. Fu J, Zhao SD, Liu HJ, Yuan QH, Liu SM, Zhang YM, Ling EA, Hao AJ. Melatonin promotes proliferation and differentiation of neural stem cells subjected to hypoxia in vitro. J Pineal Res. 2011;51(1):104–12.

    Article  CAS  PubMed  Google Scholar 

  100. Ramos E, Patiño P, Reiter RJ, Gil-Martín E, Marco-Contelles J, Parada E, Los Rios C, Romero A, Egea J. Ischemic brain injury: new insights on the protective role of melatonin. Free Radic Biol Med. 2017;104:32–53.

    Article  CAS  PubMed  Google Scholar 

  101. Yu X, Li Z, Zheng H, Ho J, Chan MT, Wu WK. Protective roles of melatonin in central nervous system diseases by regulation of neural stem cells. Cell Prolif. 2017;50(2) https://doi.org/10.1111/cpr.12323. Epub 2016 Dec 12.

    Article  PubMed Central  Google Scholar 

  102. Srinivasan V, Gobbi G. In: Shillcutt SD, Suzen S, editors. Melatonin: therapeutic value and neuroprotection. Boca Raton: CRC Press of Taylor & Francis Group; 2015.

    Google Scholar 

  103. Venkataramanujam S, Brzezinski A, Oter S, Shillcutt SD, editors. Melatonin and melatonergic drugs in clinical practice. Berlin: Springer; 2014.

    Google Scholar 

  104. Boutin JA. Quinone reductase 2 as a promising target of melatonin therapeutic actions. Expert Opin Ther Targets. 2016;20(3):303–17.

    Article  CAS  PubMed  Google Scholar 

  105. Bahna SG, Niles LP. Epigenetic regulation of melatonin receptors in neuropsychiatric disorders. Br J Pharmacol. 2017; https://doi.org/10.1111/bph.14058. [Epub ahead of print].

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Voiculescu SE, Rosca AE, Zeca V, Zagrean L, Zagrean AM. Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring. J Med Life. 2015;8(2):202–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Schwartz PJ. Season of birth in schizophrenia: a maternal-fetal chronobiological hypothesis. Med Hypotheses. 2011;76(6):785–93.

    Article  PubMed  Google Scholar 

  108. Tsuchiya KJ, Byrne M, Mortensen PB. Risk factors in relation to an emergence of bipolar disorder: a systematic review. Bipolar Disord. 2003;5(4):231–42.

    Article  PubMed  Google Scholar 

  109. Döme P, Kapitány B, Ignits G, Rihmer Z. Season of birth is significantly associated with the risk of completed suicide. Biol Psychiatry. 2010;68(2):148–55.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery and Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Joseph Wai-Hin Leung

  2. Department of Special Education and Counselling, The Education University of Hong Kong, Ting Kok, New Territories, Hong Kong

    Way Kwok-Wai Lau

  3. Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Polytechnic University of Hong Kong, Kowloon, Hong Kong

    Benson W-M. Lau & Benjamin K. Yee

Authors
  1. Joseph Wai-Hin Leung
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  2. Way Kwok-Wai Lau
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  3. Benson W-M. Lau
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  4. Benjamin K. Yee
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Corresponding authors

Correspondence to Benson W-M. Lau or Benjamin K. Yee .

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Editors and Affiliations

  1. Cathedra of Psychopathology, Catholic University of Argentina, Mendoza, Argentina

    Pascual Ángel Gargiulo

  2. Laboratory of Neurosciences and Experimental Psychology, Area of Pharmacology, Department of Pathology, National University of Cuyo, Council of Scientific and Technological Research (CONICET), Mendoza, Argentina

    Humberto Luis Mesones Arroyo

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Leung, J.WH., Lau, W.KW., Lau, B.WM., Yee, B.K. (2019). A Commentary on the Therapeutic Potential of Melatonin and Its Analogues in CNS Conditions. In: Gargiulo, P., Mesones Arroyo, H. (eds) Psychiatry and Neuroscience Update . Springer, Cham. https://doi.org/10.1007/978-3-319-95360-1_15

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  • DOI: https://doi.org/10.1007/978-3-319-95360-1_15

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