Histamine H2 receptor negatively regulates oligodendrocyte differentiation in neonatal hypoxic-ischemic white matter injury.
Histamine H2 receptor negatively regulates oligodendrocyte differentiation in neonatal hypoxic-ischemic white matter injury.
复制标题
组胺 H2 受体负向调节新生儿缺氧缺血性白质损伤中的少突胶质细胞分化。
DOI：
10.1084/jem.20191365
复制
发表时间：
2021-01-04
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Jiang L;Cheng L;Chen H;Dai H;An D;Ma Q;Zheng Y;Zhang X;Hu W;Chen Z
本研究表明，在新生儿缺氧缺血性白色损伤中，少突胶质细胞中组胺H2受体通过作用于Wnt/β-catenin信号通路负性调节其分化和髓鞘再生。H2受体拮抗剂对新生儿缺氧缺血性脑病可能具有潜在的治疗价值。新生儿缺氧缺血性脑病（hypoxic-ischemic encephalopathy，HIE）以白色物质损伤为病理特征，常导致终生的认知和神经行为功能障碍，但目前尚无促进髓鞘再生的相关治疗方法。我们发现，组胺H2受体（H2 R）负调控少突胶质细胞的分化率，而不影响少突胶质细胞在少突胶质细胞前体细胞阶段或成熟阶段后，在体外氧-葡萄糖剥夺。值得注意的是，选择性缺失H2 R基因（Hrh 2）在分化少突胶质细胞（Hrh 2fl/fl;CNPase-Cre）改善其分化，髓鞘再生和功能恢复后，新生儿缺氧缺血小鼠。H2 R对少突胶质细胞分化的调节是通过与Axin 2结合介导的，这导致Wnt/β-catenin信号通路的上调。此外，H2 R拮抗剂还促进了少突胶质细胞的分化和髓鞘再生以及新生儿缺氧缺血后认知和运动功能的恢复。因此，少突胶质细胞中的组胺H2 R可作为新生儿缺氧缺血后少突胶质细胞分化和髓鞘再生延迟的新的和有效的治疗靶点。H2 R拮抗剂对新生儿HIE有潜在的治疗价值。
This study demonstrated that histamine H2 receptor in oligodendrocytes negatively regulates its differentiation and remyelination in neonatal hypoxic-ischemic white matter injury through acting on the Wnt/β-catenin signaling pathway. The H2 receptor antagonists may have potential therapeutic value for neonatal hypoxic-ischemic encephalopathy. Neonatal hypoxic-ischemic encephalopathy (HIE) with the pathological characteristic of white matter injury often leads to lifelong cognitive and neurobehavioral dysfunction, but relevant therapies to promote remyelination are still unavailable. We found that histamine H2 receptor (H2R) negatively regulated the oligodendrocyte differentiation rate without affecting the oligodendrocytes at the oligodendrocyte precursor cell stage or mature stage following oxygen-glucose deprivation in vitro. Notably, selective deletion of the H2R gene (Hrh2) in differentiating oligodendrocytes (Hrh2fl/fl;CNPase-Cre) improved their differentiation, remyelination, and functional recovery following neonatal hypoxia-ischemia in mice. The regulation of oligodendrocyte differentiation by H2R is mediated by binding with Axin2, which leads to up-regulation of the Wnt/β-catenin signaling pathway. Furthermore, H2R antagonists also promoted oligodendrocyte differentiation and remyelination and the recovery of cognition and motor functions following neonatal hypoxia-ischemia. Thus, histamine H2R in oligodendrocytes could serve as a novel and effective therapeutic target for the retard of oligodendrocyte differentiation and remyelination following neonatal hypoxia-ischemia. The H2R antagonists may have potential therapeutic value for neonatal HIE.
登录
查看更多内容
影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
14.5
作者：
Cree, Bruce A. C.;Niu, Jianqin;Fancy, Stephen P. J.
通讯作者：
Fancy, Stephen P. J.
影响因子：
6.4
作者：
Billiards, Saraid S.;Haynes, Robin L.;Kinney, Hannah C.
通讯作者：
Kinney, Hannah C.
组胺通过 H2 受体/环磷酸腺苷/蛋白激酶 A 和 H3 受体/GABA 释放途径保护培养的皮质神经元免受 NMDA 诱导的坏死
影响因子：
4.7
作者：
Dai, H;Zhang, Z;Chen, Z
通讯作者：
Chen, Z