Lundberg Johan, Karimi Mohsen, von Gertten Christina, Holmin Staffan, Ekström Tomas J, Sandberg-Nordqvist Ann-Christin
Department of Clinical Neuroscience, Karolinska Institutet, Section of Clinical CNS research, Karolinska University Hospital, Stockholm, Sweden.
Neurosci Lett. 2009 Jun 19;457(1):8-11. doi: 10.1016/j.neulet.2009.03.105. Epub 2009 Apr 5.
Secondary cerebral damage after traumatic brain injury (TBI) occurs following processes partly initiated by gene expression alterations. DNA methylation in promoter regions is one of several epigenetic modifications, that affect the regulation of gene expression and which is a part of the pathophysiological pathway following TBI. We have investigated expression and cellular localization of DNA-methyltransferase (Dnmts) enzymes by immunohistochemistry (IHC) and confocal microscopy. Nuclear as well as cytoplasmic Dnmt1 was observed in astrocytes, in contrast to its normal neuronal nuclear localization. Interestingly, double staining with Dnmt1 and nestin showed co-localization in some reactive astrocytes in the nucleus alone, while in others this expression pattern was evident both in the nucleus and cytoplasm, in a brain region specific manner. In normal brains, and contralateral to the injury, the great majority of Dnmt1 positive cells were neurons. We also observed cytoplasmic Dnmt1 in peri-ventricular nestin expressing cells. Our findings may form the basis for further epigenetic studies following TBI and new therapeutic strategies to treat TBI patients.
创伤性脑损伤（TBI）后的继发性脑损伤发生在部分由基因表达改变引发的过程之后。启动子区域的DNA甲基化是几种表观遗传修饰之一，它影响基因表达的调控，并且是TBI后病理生理途径的一部分。我们通过免疫组织化学（IHC）和共聚焦显微镜研究了DNA甲基转移酶（Dnmts）的表达和细胞定位。与正常神经元的核定位不同，在星形胶质细胞中观察到了核内以及胞质中的Dnmt1。有趣的是，Dnmt1与巢蛋白的双重染色显示，仅在一些反应性星形胶质细胞的细胞核中有共定位，而在其他细胞中，这种表达模式在细胞核和细胞质中均以脑区特异性方式明显可见。在正常大脑以及损伤对侧，绝大多数Dnmt1阳性细胞是神经元。我们还在脑室周围表达巢蛋白的细胞中观察到了胞质Dnmt1。我们的发现可能为TBI后的进一步表观遗传学研究以及治疗TBI患者的新治疗策略奠定基础。
