Jiang Ting, Zhang Liying, Pan Xiaona, Zheng Haiqing, Chen Xi, Li Lili, Luo Jing, Hu Xiquan
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cell Neurosci. 2017 Dec 22;11:404. doi: 10.3389/fncel.2017.00404. eCollection 2017.
Myelin is closely associated with cognitive function and is extremely vulnerable to damage in ischemic cerebrovascular diseases. The failure of remyelination is mainly due to limitations in oligodendrocyte progenitor cells (OPCs) differentiation in the damaged area. Previous studies have shown that physical exercise can improve vascular cognitive impairment, but whether it can reverse the defect in remyelination during ischemic injury and the underlying mechanism remains unclear. In this study, we observed the effects of physical exercise on chronic cerebral hypoperfusion (CCH) established by bilateral carotid artery occlusion. The cognitive function, myelin integrity, OPCs proliferation and differentiation, as well as microglia polarization were analyzed at 28 days after CCH. Besides, the expression of CX3CL1/CX3CR1 axis and activation of mitogen-activated protein kinase (MAPK) signal cascades were also evaluated. We found that physical exercise improved the cognitive function of rats with CCH, alleviated myelin injury, triggered OPCs proliferation and differentiation, facilitated microglia polarization toward M2, augmented the expression of CX3CL1/CX3CR1 axis, and reduced ERK and JNK phosphorylation. The results indicated that physical exercise improved the cognitive function of rats with CCH, possibly through microglial phenotype modulation and enhancement of oligodendrocytegenesis and remyelination. Moreover, the CX3CL1/CX3CR1 axis played an important role in this process by mediating ERK- and JNK-dependent pathways.
髓磷脂与认知功能密切相关，在缺血性脑血管疾病中极易受损。髓鞘再生失败主要是由于受损区域少突胶质前体细胞（OPCs）分化受限。先前的研究表明，体育锻炼可以改善血管性认知障碍，但它是否能逆转缺血性损伤期间的髓鞘再生缺陷及其潜在机制仍不清楚。在本研究中，我们观察了体育锻炼对双侧颈动脉闭塞所致慢性脑灌注不足（CCH）的影响。在CCH后28天分析认知功能、髓磷脂完整性、OPCs增殖和分化以及小胶质细胞极化。此外，还评估了CX3CL1/CX3CR1轴的表达和丝裂原活化蛋白激酶（MAPK）信号级联的激活。我们发现，体育锻炼改善了CCH大鼠的认知功能，减轻了髓鞘损伤，触发了OPCs增殖和分化，促进小胶质细胞向M2极化，增加了CX3CL1/CX3CR1轴的表达，并降低了ERK和JNK的磷酸化。结果表明，体育锻炼可能通过调节小胶质细胞表型以及增强少突胶质细胞生成和髓鞘再生来改善CCH大鼠的认知功能。此外，CX3CL1/CX3CR1轴通过介导ERK和JNK依赖性途径在这一过程中发挥重要作用。
