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The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures.
- Source :
-
Genes [Genes (Basel)] 2020 Sep 18; Vol. 11 (9). Date of Electronic Publication: 2020 Sep 18. - Publication Year :
- 2020
-
Abstract
- Depression is the serious mental disorder. Previous studies suggest that the development mechanism of depression may be associated with disorders of the tryptophan catabolic pathway (TRYCAT). Thus, this study investigates the effect of agomelatine treatment on the expression and methylation status of genes involved in TRYCAT in the brain and blood of rats exposed to a chronic mild stress (CMS). Separate groups of rats were exposed to CMS for two or seven weeks; the second group received vehicle or agomelatine for five weeks. After completion of both stress conditions and treatment, the expression levels of messenger RNA (mRNA) and protein, as well as the methylation status of promoters, were measured in peripheral blood mononuclear cells (PBMCs) and in brain structures with the use of TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques. In PBMCs, Kmo mRNA expression increased in the group after CMS, while this effect was normalized by agomelatine therapy. In brain, KatI and KatII expression changed following CMS exposure. Moreover, CMS decreased the methylation status of the second Tdo2 promoter in the amygdala. Protein expression of Tph1, Tph2, Ido1, and KatII changed in the group after CMS and agomelatine administration, most prominently in the basal ganglia, cerebral cortex, hippocampus, and amygdala. The results indicate that CMS and agomelatine affect the mRNA and protein expression, as well as the methylation of promoters of genes involved in the tryptophan catabolic pathway.
- Subjects :
- Acetyltransferases genetics
Acetyltransferases metabolism
Animals
Brain drug effects
Brain metabolism
Chronic Disease
Hypnotics and Sedatives pharmacology
Indoleamine-Pyrrole 2,3,-Dioxygenase genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Male
Rats
Rats, Wistar
Tryptophan Hydroxylase genetics
Tryptophan Hydroxylase metabolism
Acetamides pharmacology
Brain pathology
DNA Methylation
Gene Expression Regulation drug effects
Leukocytes, Mononuclear pathology
Stress, Psychological physiopathology
Tryptophan metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4425
- Volume :
- 11
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- 32962062
- Full Text :
- https://doi.org/10.3390/genes11091093