Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.
Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.
复制标题
星形胶质细胞衍生的促炎细胞因子诱导缺氧新生儿脑室周白质髓鞘形成不足。
DOI：
10.1371/journal.pone.0087420
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Charanjit K
中科院分区：
文献类型：
--
作者：
Deng Y;Xie D;Fang M;Zhu G;Chen C;Zeng H;Lu J;Charanjit K
在围产期暴露于低钾会导致脑室周围白色物质损伤（PWMD），这是一种与髓鞘形成异常相关的疾病。缺氧条件下，新生儿脑PWM内胶质细胞被激活并释放大量炎症介质，可能导致少突胶质细胞（OL）丢失和轴突损伤。本研究旨在确定星形胶质细胞是否被激活并产生促炎细胞因子，这些细胞因子可能与缺氧PWMD中观察到的少突胶质细胞丢失和髓鞘形成不足有关。将24只1日龄Wistar大鼠暴露于缺氧2 h。然后在处死前，让大鼠在常氧条件下恢复7或28天。另一组24只被关在室外的大鼠被用作年龄匹配的对照组。免疫荧光、免疫印迹和真实的实时RT-PCR检测结果显示，P7缺氧大鼠PWM星形胶质细胞TNF-α和IL-1β表达上调。这与APC+ OL中的凋亡和TNF-R1和IL-1 R1的表达增强有关。P28 d缺氧大鼠PWM PLP表达明显减少。电镜观察有髓轴突的比例明显减少，平均g-比率在P28 d缺氧大鼠中较高。缺氧条件下，原代培养的星形胶质细胞中TNF-α和IL-1β的表达上调，原代培养的APC+少突胶质细胞中TNF-α和IL-1β的表达上调。我们的结果表明，缺氧损伤后，新生大鼠PWM中的星形胶质细胞产生炎性细胞因子，如TNF-α和IL-1β，这些炎性细胞因子通过与其相关的相应受体诱导OL的凋亡。这导致缺氧大鼠PWM中的髓鞘形成不足。
Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD), a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL) loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM) and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.
登录
查看更多内容
DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
4.8
作者：
Delgado, M;Ganea, D
通讯作者：
Ganea, D
影响因子：
6.2
作者：
Dheen, ST;Jun, Y;Ling, EA
通讯作者：
Ling, EA
DOI：
10.1097/00005373-199507000-00015
发表时间：
1995-07-01
影响因子：
--
作者：
CINAT, M;WAXMAN, K;TOMINAGA, GT
通讯作者：
TOMINAGA, GT