Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression

Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic mel...

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Main Authors: Monika Dmitrzak-Weglarz, Ewa Banach, Karolina Bilska, Beata Narozna, Aleksandra Szczepankiewicz, Edyta Reszka, Ewa Jablonska, Paweł Kapelski, Maria Skibinska, Joanna Pawlak
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.666541/full
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spelling doaj-b60b103d00f84824bc3dfb5f3b1ebf572021-04-26T07:40:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.666541666541Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar DepressionMonika Dmitrzak-Weglarz0Ewa Banach1Karolina Bilska2Beata Narozna3Aleksandra Szczepankiewicz4Edyta Reszka5Ewa Jablonska6Paweł Kapelski7Maria Skibinska8Joanna Pawlak9Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, PolandLaboratory of Neurobiology, Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, PolandDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, PolandLaboratory of Molecular and Cell Biology, Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poznan, PolandLaboratory of Molecular and Cell Biology, Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poznan, PolandDepartment of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, PolandDepartment of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, PolandDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, PolandDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, PolandDepartment of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, PolandMelatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.https://www.frontiersin.org/articles/10.3389/fphar.2021.666541/fullunipolar and bipolar depressionmelatonin pathwaycandidate gene polymorphismmelatonin metabolite serum leveltranscriptomic profiles
collection DOAJ
language English
format Article
sources DOAJ
author Monika Dmitrzak-Weglarz
Ewa Banach
Karolina Bilska
Beata Narozna
Aleksandra Szczepankiewicz
Edyta Reszka
Ewa Jablonska
Paweł Kapelski
Maria Skibinska
Joanna Pawlak
spellingShingle Monika Dmitrzak-Weglarz
Ewa Banach
Karolina Bilska
Beata Narozna
Aleksandra Szczepankiewicz
Edyta Reszka
Ewa Jablonska
Paweł Kapelski
Maria Skibinska
Joanna Pawlak
Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
Frontiers in Pharmacology
unipolar and bipolar depression
melatonin pathway
candidate gene polymorphism
melatonin metabolite serum level
transcriptomic profiles
author_facet Monika Dmitrzak-Weglarz
Ewa Banach
Karolina Bilska
Beata Narozna
Aleksandra Szczepankiewicz
Edyta Reszka
Ewa Jablonska
Paweł Kapelski
Maria Skibinska
Joanna Pawlak
author_sort Monika Dmitrzak-Weglarz
title Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
title_short Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
title_full Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
title_fullStr Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
title_full_unstemmed Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
title_sort molecular regulation of the melatonin biosynthesis pathway in unipolar and bipolar depression
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2021-04-01
description Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.
topic unipolar and bipolar depression
melatonin pathway
candidate gene polymorphism
melatonin metabolite serum level
transcriptomic profiles
url https://www.frontiersin.org/articles/10.3389/fphar.2021.666541/full
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