Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression
Autor: | Edyta Reszka, Joanna Pawlak, Karolina Bilska, Ewa Jabłońska, Aleksandra Szczepankiewicz, Monika Dmitrzak-Weglarz, Beata Narozna, Maria Skibinska, Ewa Banach, Pawel Kapelski |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty AANAT RM1-950 unipolar and bipolar depression Biological pathway Melatonin 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Agomelatine Pharmacology (medical) melatonin metabolite serum level Circadian rhythm Original Research Pharmacology business.industry Gene expression profiling candidate gene polymorphism 030104 developmental biology Endocrinology melatonin pathway Therapeutics. Pharmacology Serotonin business transcriptomic profiles hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug Hormone |
Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
ISSN: | 1663-9812 |
Popis: | 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. |
Databáze: | OpenAIRE |
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