二氮嗪在常氧和慢性亚致死性缺氧条件下促进新生大鼠脑内少突胶质细胞分化。
Diazoxide promotes oligodendrocyte differentiation in neonatal brain in normoxia and chronic sublethal hypoxia.
作者信息
Zhu Ying, Wendler Christopher C, Shi Olivia, Rivkees Scott A
机构信息
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
出版信息
Brain Res. 2014 Oct 24;1586:64-72. doi: 10.1016/j.brainres.2014.08.046. Epub 2014 Aug 23.
Periventricular white matter injury (PWMI) is the most common cause of brain injury in preterm infants. It is believed that loss of late oligodendrocyte progenitor cells (OPCs) and disrupted maturation of oligodendrocytes contributes to defective myelination in PWMI. At present, no clinically approved drugs are available for treating PWMI. Previously, we found that diazoxide promotes myelination and attenuates brain injury in the chronic sublethal hypoxia model of PWMI. In this study, we investigated the mechanisms by which diazoxide promotes myelination. We observed that diazoxide increases the ratio of differentiated oligodendrocytes in the cerebral white matter, promotes the expression of differentiation-associated transcriptional factors Nkx2.2 and Sox10, and increases the expression of myelin genes CNP and MBP. These results show that diazoxide promotes oligodendrocyte differentiation in the developing brain.
脑室周围白质损伤（PWMI）是早产儿脑损伤的最常见原因。据信，晚期少突胶质前体细胞（OPC）的丢失和少突胶质细胞成熟的破坏导致了PWMI中髓鞘形成缺陷。目前，尚无临床批准的药物可用于治疗PWMI。此前，我们发现二氮嗪在PWMI的慢性亚致死性缺氧模型中可促进髓鞘形成并减轻脑损伤。在本研究中，我们研究了二氮嗪促进髓鞘形成的机制。我们观察到二氮嗪增加了脑白质中分化少突胶质细胞的比例，促进了分化相关转录因子Nkx2.2和Sox10的表达，并增加了髓鞘基因CNP和MBP的表达。这些结果表明，二氮嗪可促进发育中大脑的少突胶质细胞分化。
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