Mfsd2a Reverses Spatial Learning and Memory Impairment Caused by Chronic Cerebral Hypoperfusion via Protection of the Blood–Brain Barrier
Mfsd2a Reverses Spatial Learning and Memory Impairment Caused by Chronic Cerebral Hypoperfusion via Protection of the Blood–Brain Barrier
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DOI：
10.3389/fnins.2020.00461
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发表时间：
2020-06
影响因子：
4.3
通讯作者：
Changhua Qu;Hao Song;Jun Shen;Linling Xu;Yaqing Li;Chujie Qu;Tian-hang Li;Junjian Zhang
中科院分区：
文献类型：
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作者：
Changhua Qu;Hao Song;Jun Shen;Linling Xu;Yaqing Li;Chujie Qu;Tian-hang Li;Junjian Zhang
血脑屏障（BBB）的破坏可导致认知障碍。主要易化蛋白超家族结构域蛋白2a（Mfsd 2a）是一种新发现的维持血脑屏障完整性所必需的蛋白。然而，Mfsd 2a在血管性认知障碍中的作用尚未被探索。本研究采用永久性双侧颈总动脉阻断（2 VO）方法建立慢性脑低灌注（CCH）大鼠模型。我们发现，在2 VO程序后，大鼠表现出认知障碍，海马内BBB渗漏增加，Mfsd 2a蛋白表达减少。在大鼠海马中Mfsd 2a的过表达逆转了这些变化。使用透射电子显微镜进行的进一步研究显示，CCH大鼠海马BBB中囊泡胞吞率显着增加; Mfsd 2a过表达后，该速率降低。此外，Mfsd 2a过表达并没有引起紧密连接相关蛋白的表达和紧密连接的超微结构的变化。总之，Mfsd 2a减轻了CCH大鼠的BBB损伤，改善了认知障碍，其对BBB的保护作用是通过抑制囊泡转胞作用实现的。
Disruption of the blood–brain barrier (BBB) can lead to cognitive impairment. Major facilitator superfamily domain-containing protein 2a (Mfsd2a) is a newly discovered protein that is essential for maintaining BBB integrity. However, the role of Mfsd2a in vascular cognitive impairment has not been explored yet. In this study, a rat model of chronic cerebral hypoperfusion (CCH) was established by producing permanent bilateral common carotid artery occlusion (2VO) in rats. We found that after the 2VO procedure, the rats exhibited cognitive impairment, showed increased BBB leakage within the hippocampus, and had reduced expression of the Mfsd2a protein. The overexpression of Mfsd2a in the rat hippocampus reversed these changes. Further investigations using transmission electron microscopy revealed a significantly increased rate of vesicular transcytosis in the BBB of the hippocampus of the CCH rats; the rate reduced after overexpression of Mfsd2a. Moreover, Mfsd2a overexpression did not cause changes in the expression of tight junction-associated proteins and in the ultrastructures of the tight junctions. In conclusion, Mfsd2a attenuated BBB damage and ameliorated cognitive impairment in CCH rats, and its protective effect on the BBB was achieved via inhibition of vesicular transcytosis.