TY - JOUR

T1 - Gene Expression Levels of DNA-Methyltransferases and Histone Deacetylases after Neonatal Dexamethasone Administration and Chronic Unpredictable Stress in Adult Rat Brainstem

AU - Kalinina, T. S.

AU - Sukhareva, E. V.

AU - Lanshakov, D. A.

AU - Bulygina, V. V.

AU - Dygalo, N. N.

N1 - Gene Expression Levels of DNA-Methyltransferases and Histone Deacetylases after Neonatal Dexamethasone Administration and Chronic Unpredictable Stress in Adult Rat Brainstem / T. S. Kalinina, E. V. Sukhareva, D. A. Lanshakov [et al.] // Neurochemical Journal. – 2025. – Vol. 19, No. 3. – P. 387-396. – DOI 10.1134/S1819712425700436. – EDN NAMHGT. The work was supported by the state assignment of the Federal Research Center of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (No. FWNR-2022-0023).

PY - 2025/11/12

Y1 - 2025/11/12

N2 - Epigenetic modifications of DNA and chromatin structure are involved in the long-term consequences of adverse events in early ontogeny. 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 which in adult animals is 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, and Dnmt3b) and histone deacetylase (Hdac1 and 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 ontogeny caused long-term changes in the expression of DNA methyltransferase and histone deacetylase genes-increased 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.

AB - Epigenetic modifications of DNA and chromatin structure are involved in the long-term consequences of adverse events in early ontogeny. 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 which in adult animals is 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, and Dnmt3b) and histone deacetylase (Hdac1 and 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 ontogeny caused long-term changes in the expression of DNA methyltransferase and histone deacetylase genes-increased 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.

KW - дексаметазон

KW - ствол головного мозга

KW - мРНК

KW - ДНК-метилтрансферазы

KW - гистоновые деацетилазы

KW - раннее воздействие

KW - стресс

KW - dexamethasone

KW - brainstem

KW - mRNA

KW - DNA-methyltransferases

KW - histone deacetylases

KW - early exposures

KW - stress

UR - https://www.mendeley.com/catalogue/4c29358c-03d2-3619-8f60-f90d53ca5e04/

UR - https://www.elibrary.ru/item.asp?id=83185744

U2 - 10.1134/s1819712425700436

DO - 10.1134/s1819712425700436

M3 - Article

VL - 19

SP - 387

EP - 396

JO - Neurochemical Journal

JF - Neurochemical Journal

SN - 1819-7124

IS - 3

ER -