DNA methylation markers in the postnatal developing rat brain.

DNA methylation markers in the postnatal developing rat brain.
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DOI:
10.1016/j.brainres.2013.08.005
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发表时间:
2013-10-02
期刊:
影响因子:
2.9
通讯作者:
Clinton SM
Clinton SM
中科院分区:
医学3区
文献类型:
--
作者:
Simmons RK;Stringfellow SA;Glover ME;Wagle AA;Clinton SM

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尽管人们对包括DNA甲基化在内的表观遗传过程如何改变可能导致精神和神经发育障碍产生了浓厚的兴趣,但对甲基化过程如何在出生后早期大脑发育期间发生变化的了解有限。本研究采用原位杂交技术研究了三种主要DNA甲基转移酶(DNMT1、DNMT3a和DNMT3b)在发育中的大鼠脑内的表达。在出生后的前三周,我们还评估了选定大脑区域的5-甲基胞嘧啶水平(全球DNA甲基化的一个指标)。DNMT1、DNMT3a和DNMT3b在成年和出生后发育的大鼠脑中广泛表达。总体而言,DNMT基因的表达水平在出生后第一周达到最高点,并在出生后前三周逐渐下降,分布在海马区、杏仁体、纹状体、扣带区和外侧隔区。全球DNA甲基化水平并不遵循这种发育模式;在出生后的前三周,海马区的甲基化水平逐渐增加,在发育中的杏仁核和前额叶皮质中保持稳定。我们的结果有助于加深对DNA甲基化标记如何在发育中的大脑中展开的理解,并强调这些发育过程在不同的大脑区域可能会有所不同。
In spite of intense interest in how altered epigenetic processes including DNA methylation may contribute to psychiatric and neurodevelopmental disorders, there is a limited understanding of how methylation processes change during early postnatal brain development. The present study used in situ hybridization to assess mRNA expression for the three major DNA methyltranserases (DNMTs) – DNMT1, DNMT3a and DNMT3b – in the developing rat brain at seven developmental timepoints: postnatal days (P) 1, 4, 7, 10, 14, 21, and 75. We also assessed 5-methylcytosine levels (an indicator of global DNA methylation) in selected brain regions during the first three postnatal weeks. DNMT1, DNMT3a and DNMT3b mRNAs are widely expressed throughout the adult and postnatal developing rat brain. Overall, DNMT mRNA levels reached their highest point in the first week of life and gradually decreased over the first three postnatal weeks within the hippocampus, amygdala, striatum, cingulate and lateral septum. Global DNA methylation levels did not follow this developmental pattern; methylation levels gradually increased over the first three postnatal weeks in the hippocampus, and remained stable in the developing amygdala and prefrontal cortex. Our results contribute to a growing understanding of how DNA methylation markers unfold in the developing brain, and highlight how these developmental processes may differ within distinct brain regions.
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