Zhang Yunpeng, Zhang Yaodong, Chen Danmei, Wang Cuiting, Chen Long, Gao Chao, Fan Wei, Shi Jimin, Zhang Jihong, Li Bing
Research Center for Clinical Medicine, Jinshan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Pediatrics, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
Front Mol Neurosci. 2019 Sep 4;12:214. doi: 10.3389/fnmol.2019.00214. eCollection 2019.
Cerebral palsy (CP) is a neurodevelopmental disorder usually occurring early in life and persisting through the whole life. Several risk factors, including perinatal hypoxia-ischemia (HI), may contribute to occurrence of CP in preterm infants. DNA hydroxymethylation has been shown to play an important role in neurodevelopment and neurodegenerative disorders. However, the effect of DNA hydroxymethylation in CP remains unknown. The aim of this study is to explore whether and how DNA hydroxymethylation is involved in CP pathogenesis. We observed that overall 5-hydroxymethylcytosine (5hmC) abundance in the cortex of the temporal lobe of rat pups was decreased significantly after hypoxic-ischemic injury, and the reduced expression of Tet1 and Tet2 enzymes might be responsible for this change. Identified differential hydroxymethylation regions (DhMRs) were richly involved in multiple signaling pathways related to neuronal development and function. Furthermore, we found that reduced 5hmC modification on the DhMRs-related genes were accompanied by decrease of their mRNA expression levels. These results suggest that 5hmC modifications are involved in the CP pathogenesis and may potentially serve as a new therapeutic target.
脑瘫（CP）是一种神经发育障碍，通常在生命早期出现并持续终生。包括围产期缺氧缺血（HI）在内的多种风险因素可能导致早产儿发生CP。DNA羟甲基化已被证明在神经发育和神经退行性疾病中起重要作用。然而，DNA羟甲基化在CP中的作用仍不清楚。本研究的目的是探讨DNA羟甲基化是否以及如何参与CP的发病机制。我们观察到，缺氧缺血损伤后，幼鼠颞叶皮质中整体5-羟甲基胞嘧啶（5hmC）丰度显著降低，Tet1和Tet2酶表达降低可能是导致这种变化的原因。鉴定出的差异羟甲基化区域（DhMRs）大量参与了与神经元发育和功能相关的多种信号通路。此外，我们发现DhMRs相关基因上5hmC修饰的减少伴随着其mRNA表达水平的降低。这些结果表明，5hmC修饰参与了CP的发病机制，并可能潜在地作为一个新的治疗靶点。
