Diazoxide promotes oligodendrocyte precursor cell proliferation and myelination.
Diazoxide promotes oligodendrocyte precursor cell proliferation and myelination.
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DOI：
10.1371/journal.pone.0010906
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发表时间：
2010-05-28
期刊：
影响因子：
3.7
通讯作者：
Rivkees SA
中科院分区：
文献类型：
--
作者：
Fogal B;McClaskey C;Yan S;Yan H;Rivkees SA
几种临床病症与白色物质损伤相关，包括脑室周围白色物质损伤（PWMI），其是早产儿持续的脑损伤的一种形式。有人认为，这种情况下的白色损伤是由于少突胶质细胞（OL）发育或死亡的改变，导致OL损失和髓鞘形成不足。目前还没有刺激OL增殖和促进髓鞘形成的药物。有证据表明，去极化刺激减少OL增殖和分化，而高胆固醇药物刺激OL增殖和分化。考虑到药物二氮嗪激活KATP通道至高增殖细胞，我们测试了该化合物是否可以影响OL增殖和髓鞘形成。使用大鼠少突胶质细胞前体细胞（OPC）的文化，小脑切片文化，并在体内模型PWMI新生小鼠暴露于慢性亚致死性缺氧（10%O2）进行研究。我们发现少突胶质细胞中表达KATP通道成分Kir 6.1和6.2以及SUR 2。此外，二氮嗪有效刺激OPC增殖，其他KATP激活剂也是如此。二氮嗪也刺激小脑切片培养的髓鞘形成。我们还发现，二氮嗪防止髓鞘形成和脑室扩大慢性亚致死性缺氧。这些结果鉴定了OL中的KATP通道组分，并表明二氮嗪可以刺激OL体外增殖。重要的是，我们发现二氮嗪可以促进体内髓鞘形成，并防止缺氧诱导的PWMI。
Several clinical conditions are associated with white matter injury, including periventricular white matter injury (PWMI), which is a form of brain injury sustained by preterm infants. It has been suggested that white matter injury in this condition is due to altered oligodendrocyte (OL) development or death, resulting in OL loss and hypomyelination. At present drugs are not available that stimulate OL proliferation and promote myelination. Evidence suggests that depolarizing stimuli reduces OL proliferation and differentiation, whereas agents that hyperpolarize OLs stimulate OL proliferation and differentiation. Considering that the drug diazoxide activates KATP channels to hyperpolarize cells, we tested if this compound could influence OL proliferation and myelination. Studies were performed using rat oligodendrocyte precursor cell (OPC) cultures, cerebellar slice cultures, and an in vivo model of PWMI in which newborn mice were exposed to chronic sublethal hypoxia (10% O2). We found that KATP channel components Kir 6.1 and 6.2 and SUR2 were expressed in oligodendrocytes. Additionally, diazoxide potently stimulated OPC proliferation, as did other KATP activators. Diazoxide also stimulated myelination in cerebellar slice cultures. We also found that diazoxide prevented hypomyelination and ventriculomegaly following chronic sublethal hypoxia. These results identify KATP channel components in OLs and show that diazoxide can stimulate OL proliferation in vitro. Importantly we find that diazoxide can promote myelination in vivo and prevent hypoxia-induced PWMI.
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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：
2.2
作者：
Jones, LJ;Gray, M;Singer, VL
通讯作者：
Singer, VL
影响因子：
5.3
作者：
Craig, A;Luo, NL;Back, SA
通讯作者：
Back, SA
影响因子：
1.7
作者：
Maysami, Samaneh;Nguyen, Dan;Stangel, Martin
通讯作者：
Stangel, Martin
影响因子：
3.6
作者：
Liu, YG;Ren, GF;Seharaseyon, J
通讯作者：
Seharaseyon, J