Aspirin promotes oligodendrocyte precursor cell proliferation and differentiation after white matter lesion.
Aspirin promotes oligodendrocyte precursor cell proliferation and differentiation after white matter lesion.
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DOI：
10.3389/fnagi.2014.00007
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发表时间：
2014
影响因子：
4.8
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Chen J;Zuo S;Wang J;Huang J;Zhang X;Liu Y;Zhang Y;Zhao J;Han J;Xiong L;Shi M;Liu Z
脑白色物质病变（WML）是认知功能障碍的主要原因之一，常由慢性脑灌注不足引起。一系列证据表明，阿司匹林具有神经保护作用，并对缺血性卒中患者的长期预后和生存产生一定的益处。然而，阿司匹林是否对WML具有保护作用仍然是未知的。在这里，我们发现阿司匹林可以促进WML后少突胶质细胞前体细胞（OPC）增殖和分化为少突胶质细胞。对雄性Sprague-Dawley大鼠进行永久性双侧颈总动脉闭塞，这是一种成熟的WML模型。4周后，Morris水迷宫实验显示大鼠学习记忆能力受损，而阿司匹林治疗可改善大鼠的行为表现。低剂量阿司匹林（25 mg/kg）可增加OPCs数量，高剂量阿司匹林（100-200 mg/kg）可增加少突胶质细胞数量，并改善WML诱导的髓鞘变薄。同样，我们的体外研究也表明，相对低和高剂量的阿司匹林分别增强OPC增殖和分化为少突胶质细胞。此外，我们发现，阿司匹林增强细胞外信号相关激酶（ERK），但抑制RhoA的活动。总之，我们提供了第一个证据表明阿司匹林可以促进WML后少突胶质细胞的发生和髓鞘形成，这可能涉及ERK和RhoA通路。
Cerebral white matter lesion (WML) is one of the main causes for cognitive impairment and is often caused by chronic cerebral hypoperfusion. A line of evidence has shown that aspirin has neuroprotective effects and produces some benefits in long-term outcome and survival for ischemic stroke patients. However, whether aspirin exerts a protective effect against WML is still largely unknown. Here, we showed that aspirin could promote oligodendrocyte precursor cell (OPC) proliferation and differentiation into oligodendrocytes after WML. Male Sprague-Dawley rats were subjected to permanent bilateral common carotid artery occlusion, a well-established model for WML. Four weeks later, Morris water maze test showed an impairment of learning and memory ability of rat while aspirin treatment improved behavioral performance. Low dose of aspirin (25 mg/kg) was found to elevate the number of OPCs while relatively high doses (100–200 mg/kg) increased that of oligodendrocytes, and ameliorated WML-induced the thinning of myelin, as revealed by the electron microscope. Similarly, our in vitro study also showed that relatively low and high doses of aspirin enhanced OPC proliferation and differentiation into oligodendrocytes, respectively. Furthermore, we revealed that aspirin enhanced extracellular signal-related kinase (ERK) but inhibited RhoA activities. In summary, we provided the first evidence that aspirin can promote oligodendrogenesis and oligodendrocyte myelination after WML, which may involve ERK and RhoA pathways.
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影响因子：
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作者：
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