Dişi Sıçanlarda Prenatal Stresin DNA Metiltransferazların ve Histon Deasetilazların Kortikal ve Hipokampal Gen Ekspresyon Profilleri Üzerindeki Etkileri

Öz

Öz Bu çalışmanın amacı, prenatal stresin (PS) dişi sıçanların serebral korteks ve hipokampüsünde DNA metiltransferazlar (DNMT) ve histon deasetilazların (HDAC) mRNA düzeylerine etkilerini araştırmaktır. PS sıçanlarda deksametazonla (Dex) indüklendi. Gebeliğin 14. gününden 21. gününe, gebe sıçanlara Dex (100 ug/kg/gün) veya salin enjekte edildi. Doğumdan sonra 3 aylıkken dişi sıçanlar (n=5) dekapite edildi. Dex'in epigenetik mekanizmalar üzerindeki etkileri gerçek zamanlı PCR ile DNMT1, DNMT3a, DNMT3b, HDAC1 ve HDAC2 mRNA düzeyleri aracılığıyla araştırıldı. İstatistiksel analizler tek yönlü varyans analiziyle yapıldı. Prenatal Dex maruziyeti, korteks ve hipokampüste DNMT3a, HDAC1 ve HDAC2 mRNA düzeylerinde anlamlı artışlara neden oldu. Ayrıca Dex grubunda DNMT3b mRNA düzeylerinin hipokampüste anlamlı bir şekilde artarken kortekste azaldığı bulundu. DNMT1 mRNA düzeylerinde anlamlı bir farklılık saptanmadı. PS'in dişi sıçanların korteks ve hipokampüsünde; DNMT3a, DNMT3b, HDAC1 ve HDAC2 genlerinin ekspresyon profillerindeki değişiklikler yoluyla epigenetik mekanizmaların düzensizliğini tetikleyebileceği sonucuna varılmıştır.

Anahtar Kelimeler

• Prenatal stres
• deksametazon
• DNA metiltransferaz
• histon deasetilaz
• dişi sıçan

The Effects of Prenatal Stress on Cortical and Hippocampal Gene Expression Profiles of DNA Methyltransferases and Histone Deacetylases in Female Rats

Öz

The aim of this study was to investigate the effects of prenatal stress (PS) on mRNA levels of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in cerebral cortex and hippocampus of female rats. PS was induced in rats with dexamethasone (Dex). From gestation day 14 to 21, pregnant rats were injected daily with Dex (100 μg/kg) or saline. After birth, at 3 months of age, female rats were decapitated (n=5). The effects of Dex on epigenetic mechanisms were investigated by real-time PCR through mRNA levels of DNMT1, DNMT3a, DNMT3b, HDAC1 and HDAC2. Statistical significant differences were determined with one-way analysis of variance. Prenatal Dex exposure caused significant increases in DNMT3a, HDAC1 and HDAC2 mRNA levels in cortex and hippocampus. We further found that DNMT3b mRNA levels significantly increased in hippocampus but decreased in cortex of Dex group. No significant differences were found in DNMT1 mRNA levels. It was concluded that PS may trigger dysregulation of epigenetic mechanisms in cortex and hippocampus of female rats through alterations in gene expression profiles of DNMT3a, DNMT3b, HDAC1 and HDAC2.

Anahtar Kelimeler

• Prenatal stress
• dexamethasone
• DNA methyltransferase
• histone deacetylase
• female rat

Kaynakça

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