Investigating the Relationship Between Neuronal Cell Death and Early DNA Methylation After Ischemic Injury.
Investigating the Relationship Between Neuronal Cell Death and Early DNA Methylation After Ischemic Injury.
复制标题
DOI：
10.3389/fnins.2020.581915
复制
发表时间：
2020
影响因子：
4.3
通讯作者：
Takagi N
中科院分区：
文献类型：
--
作者：
Asada M;Hayashi H;Murakami K;Kikuiri K;Kaneko R;Yuan B;Takagi N
脑缺血可导致神经细胞死亡，引起各种脑功能障碍。因此，防止神经细胞死亡对保护大脑至关重要。另一方面，有报道称，包括DNA甲基化在内的表观遗传学在癌症等疾病的发病机制中起着关键作用。越来越多的证据表明，DNA甲基化异常与细胞死亡有关。然而，脑缺血后DNA甲基化的机制尚不完全清楚。本研究旨在探讨DNA甲基化与脑缺血后神经细胞死亡的关系。采用短暂性大脑中动脉闭塞再灌注(MCAO/R)模型大鼠和N-甲基-D-天冬氨酸(NMDA)处理的原代培养大鼠皮质神经元，检测缺血条件下DNA甲基化情况。在这项研究中，我们证明了在MCAO/R后24小时，这些神经元的DNA甲基化增加，并且NMDA处理后立即这些神经元的DNA甲基化增加，可能是通过激活DNA甲基转移酶(DNMT)3a。此外，NMDA处理的神经元可以通过DNMT抑制剂的处理来保护，同时伴随着DNA甲基化的抑制。我们的结果表明，DNA甲基化将是神经细胞死亡的启动因素，抑制这种甲基化可能成为治疗中风的有效策略。
Cerebral ischemia induces neuronal cell death and causes various kinds of brain dysfunction. Therefore, prevention of neuronal cell death is most essential for protection of the brain. On the other hand, it has been reported that epigenetics including DNA methylation plays a pivotal role in pathogenesis of some diseases such as cancer. Accumulating evidences indicate that aberrant DNA methylation is related to cell death. However, DNA methylation after cerebral ischemia has not been fully understood yet. The aim of this present study was to investigate the relationships between DNA methylation and neuronal cell death after cerebral ischemia. We examined DNA methylation under the ischemic condition by using transient middle cerebral artery occlusion and reperfusion (MCAO/R) model rats and N-methyl-D-aspartate (NMDA)–treated cortical neurons in primary culture. In this study, we demonstrated that DNA methylation increased in these neurons 24 h after MCAO/R and that DNA methylation, possibly through activation of DNA methyltransferases (DNMT) 3a, increased in such neurons immediately after NMDA treatment. Furthermore, NMDA-treated neurons were protected by treatment with a DNMT inhibitor that were accompanied by inhibition of DNA methylation. Our results showed that DNA methylation would be an initiation factor of neuronal cell death and that inhibition of such methylation could become an effective therapeutic strategy for stroke.
登录
查看更多内容
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
6.3
作者：
Hu, Chaur-Jong;Chen, Shang-Der;Hsu, Chung Y.
通讯作者：
Hsu, Chung Y.
影响因子：
8.3
作者：
Morris-Blanco, Kahlilia C.;Kim, TaeHee;Vemuganti, Raghu
通讯作者：
Vemuganti, Raghu
影响因子：
9
作者：
Farinelli P;Perera A;Arango-Gonzalez B;Trifunovic D;Wagner M;Carell T;Biel M;Zrenner E;Michalakis S;Paquet-Durand F;Ekström PA
通讯作者：
Ekström PA