Gene Expression Levels of DNA-Methyltransferases and Histone Deacetylases After Neonatal Dexamethasone Administration and Chronic Unpredictable Stress in Adult Rat Brainstem

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Abstract

Epigenetic modifications of DNA and chromatin structure are involved in the long-term consequences of adverse early ontogenesis events. Increased glucocorticoid levels due to stress or hormonal therapy in early life provoke the development of autism spectrum disorders, attention deficit syndrome, and increase with age the susceptibility to depressive-anxiety disorders in adult animals regulated by the noradrenergic and serotonergic systems, the perikarya of which are localized in the brainstem. The aim of the study was to determine the expression levels of DNA methyltransferase (Dnmt1, Dnmt3a, Dnmt3b) and histone deacetylase (Hdac1, Hdac2) genes in the brainstem of adult two-month-old rats after a single administration of the glucocorticoid receptor agonist dexamethasone (0.2 mg/kg) on the 3rd day of life, as well as the effects of chronic unpredictable stress in the late adolescent period of development (from 45 to 60 days of life). It was established that neonatal administration of a glucocorticoid receptor agonist in the sensitive period of early postnatal ontogenesis causes long-term changes in the expression of DNA methyltransferase and histone deacetylase genes - increases the mRNA levels of the Dnmt3a, Dnmt3b and Hdca1 genes in the brainstem of adult animals. The induction of expression of the main regulators of DNA methylation and chromatin conformation, which was established for the first time, is preserved for the Dnmt3b and Hdca1 genes under the influence of chronic unpredictable stress. The revealed patterns can provide a decrease in the expression of epigenetically regulated transcripts in the brainstem, which is important for understanding the mechanism of long-term consequences of unfavorable conditions of early development.

About the authors

T. S Kalinina

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Email: kalin@bionet.nsc.ru
Novosibirsk, Russia; Novosibirsk, Russia

E. V Sukhareva

Institute of Cytology and Genetics, Siberian Branch of RAS

Novosibirsk, Russia

D. A Lanshakov

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Novosibirsk, Russia; Novosibirsk, Russia

V. V Bulygina

Institute of Cytology and Genetics, Siberian Branch of RAS

Novosibirsk, Russia

N. N Dygalo

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Novosibirsk, Russia; Novosibirsk, Russia

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