학술논문
Prenatal Dexamethasone Exposure in Male Rats Alters Gene Expression Patterns of Epigenetic Enzymes in Hippocampus and Cortex
Original Article
Original Article
Document Type
Report
Source
European Journal of Therapeutics. September 2022, Vol. 28 Issue 3, p219, 7 p.
Subject
Language
English
ISSN
2564-7784
Abstract
INTRODUCTION The brain is vulnerable to stress factors during the perinatal life due to its high neuroplasticity. Prenatal exposure to environmental factors is assumed to change gene expression profiles throughout [...]
Objective: This study aimed to examine the effects of prenatal stress (PS) induced by dexamethasone exposure on gene expression levels of epigenetic enzymes in hippocampus and cerebral cortex of male rats through relative mRNA levels of histone acetyltransferases (activating transcription factor 2, P300), histone deacetylases (HDAC1, HDAC2), and DNA methyltransferases (DNMT1, DNMT3a, DNMT3b). Methods: Pregnant rats were daily injected subcutaneously with dexamethasone (0.2 mg/kg) or saline during the third week of gestation. After birth, male rats were killed at 90 days of age (n = 5 for control and dexamethasone groups). Hippocampal and cortical tissues were used for gene expression analyses. The effects of dexamethasone on epigenetic mechanisms were investigated by real-time polymerase chain reaction through relative mRNA levels of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Statistical comparisons were performed with Student's t-test. Results: Prenatal dexamethasone exposure (PDE) caused increased DNMT1, DNMT3a, DNMT3b, activating transcription factor 2 and decreased P300 mRNA levels in hippocampus while increased DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2 mRNA levels were achieved in cortex. Furthermore, no significant differences were obtained in cortical DNMT1 and hippocampal HDAC1 and HDAC2 gene expression levels between control and prenatally stressed rats. Conclusion: Our results emphasize the effect of prenatal dexamethasone exposure on gene expression levels of epigenetic enzymes involved in histone acety latio n/dea cetyl ation and DNA methylation in male rats and suggest that prenatal stress may lead to epigenetic dysregulation through alterations in hippocampal and cortical gene expression patterns of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Keywords: Dexamethasone, epigenetic enzymes, prenatal stress, rat
Objective: This study aimed to examine the effects of prenatal stress (PS) induced by dexamethasone exposure on gene expression levels of epigenetic enzymes in hippocampus and cerebral cortex of male rats through relative mRNA levels of histone acetyltransferases (activating transcription factor 2, P300), histone deacetylases (HDAC1, HDAC2), and DNA methyltransferases (DNMT1, DNMT3a, DNMT3b). Methods: Pregnant rats were daily injected subcutaneously with dexamethasone (0.2 mg/kg) or saline during the third week of gestation. After birth, male rats were killed at 90 days of age (n = 5 for control and dexamethasone groups). Hippocampal and cortical tissues were used for gene expression analyses. The effects of dexamethasone on epigenetic mechanisms were investigated by real-time polymerase chain reaction through relative mRNA levels of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Statistical comparisons were performed with Student's t-test. Results: Prenatal dexamethasone exposure (PDE) caused increased DNMT1, DNMT3a, DNMT3b, activating transcription factor 2 and decreased P300 mRNA levels in hippocampus while increased DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2 mRNA levels were achieved in cortex. Furthermore, no significant differences were obtained in cortical DNMT1 and hippocampal HDAC1 and HDAC2 gene expression levels between control and prenatally stressed rats. Conclusion: Our results emphasize the effect of prenatal dexamethasone exposure on gene expression levels of epigenetic enzymes involved in histone acety latio n/dea cetyl ation and DNA methylation in male rats and suggest that prenatal stress may lead to epigenetic dysregulation through alterations in hippocampal and cortical gene expression patterns of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Keywords: Dexamethasone, epigenetic enzymes, prenatal stress, rat