Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression

The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian s...

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Published inJournal of affective disorders Vol. 148; no. 2-3; pp. 357 - 367
Main Authors Wu, Ying-Hui, Ursinus, Jeanine, Zhou, Jiang-Ning, Scheer, Frank A.J.L., Ai-Min, Bao, Jockers, Ralf, van Heerikhuize, Joop, Swaab, Dick F.
Format Journal Article
LanguageEnglish
Published Oxford Elsevier B.V 01.06.2013
Elsevier
Subjects
Adult and adolescent clinical studies
Affective disorders
Aged
Aged, 80 and over
Biological and medical sciences
Bipolar affective disorder
Bipolar depression
Bipolar Disorder - metabolism
Bipolar Disorder - physiopathology
Bipolar disorders
Brain
Case-Control Studies
Circadian Rhythm - physiology
Depression
Depressive Disorder, Major - metabolism
Depressive Disorder, Major - physiopathology
Feedback
Female
Human hypothalamus
Humans
Immunocytochemistry
Immunohistochemistry
Major depression
Male
Medical sciences
Melatonin
Melatonin - metabolism
Melatonin receptor
Middle Aged
Mood disorders
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptor, Melatonin, MT1 - metabolism
Receptor, Melatonin, MT2 - metabolism
Suprachiasmatic nucleus
Suprachiasmatic Nucleus - metabolism
Vasoactive Intestinal Peptide - metabolism
Vasopressins - metabolism
Suprachiasmatic nucleus
Human hypothalamus
Major depression
Immunocytochemistry
Bipolar depression
Melatonin receptor
Mood disorder
Human
Central nervous system
Depression
Bipolar disorder
Hypothalamus
Encephalon
Anatomic pathology
Online AccessGet full text
ISSN0165-0327
1573-2517
1573-2517
DOI10.1016/j.jad.2012.12.025

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Abstract The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
AbstractList The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression.BACKGROUNDThe pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression.In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry.METHODIn order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry.We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.RESULTSWe show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
Background: The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. Method: In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. Results: We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. Conclusion and limitations Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
Abstract Background The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. Method In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. Results We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. Conclusion and limitations Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.
Background: The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression. Method: In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry. Results: We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. Conclusion and limitations Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively. [Copyright Elsevier B.V.]
Author Wu, Ying-Hui
Scheer, Frank A.J.L.
Zhou, Jiang-Ning
Jockers, Ralf
Ursinus, Jeanine
Ai-Min, Bao
van Heerikhuize, Joop
Swaab, Dick F.
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  givenname: Jiang-Ning
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  fullname: Zhou, Jiang-Ning
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  givenname: Frank A.J.L.
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  givenname: Ralf
  surname: Jockers
  fullname: Jockers, Ralf
  organization: Department of Cell Biology, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm, U567 Paris, France
– sequence: 7
  givenname: Joop
  surname: van Heerikhuize
  fullname: van Heerikhuize, Joop
  organization: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Science, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands
– sequence: 8
  givenname: Dick F.
  surname: Swaab
  fullname: Swaab, Dick F.
  email: d.f.swaab@nin.knaw.nl
  organization: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Science, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands
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ISSN 0165-0327
1573-2517
IngestDate Sun Sep 28 06:49:23 EDT 2025
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Thu Apr 24 22:57:13 EDT 2025
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Tue Aug 26 17:09:16 EDT 2025
IsPeerReviewed true
IsScholarly true
Issue 2-3
Keywords Suprachiasmatic nucleus
Human hypothalamus
Major depression
Immunocytochemistry
Bipolar depression
Melatonin receptor
Mood disorder
Human
Central nervous system
Depression
Bipolar disorder
Hypothalamus
Encephalon
Anatomic pathology
Language English
License CC BY 4.0
Copyright © 2013 Elsevier B.V. All rights reserved.
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Snippet The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic...
Abstract Background The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the...
Background: The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic...
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SubjectTerms Adult and adolescent clinical studies
Affective disorders
Aged
Aged, 80 and over
Biological and medical sciences
Bipolar affective disorder
Bipolar depression
Bipolar Disorder - metabolism
Bipolar Disorder - physiopathology
Bipolar disorders
Brain
Case-Control Studies
Circadian Rhythm - physiology
Depression
Depressive Disorder, Major - metabolism
Depressive Disorder, Major - physiopathology
Feedback
Female
Human hypothalamus
Humans
Immunocytochemistry
Immunohistochemistry
Major depression
Male
Medical sciences
Melatonin
Melatonin - metabolism
Melatonin receptor
Middle Aged
Mood disorders
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptor, Melatonin, MT1 - metabolism
Receptor, Melatonin, MT2 - metabolism
Suprachiasmatic nucleus
Suprachiasmatic Nucleus - metabolism
Vasoactive Intestinal Peptide - metabolism
Vasopressins - metabolism
Title Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression
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https://www.ncbi.nlm.nih.gov/pubmed/23357659
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