Extracellular vesicles of the blood-brain barrier: Role in the HIV-1 associated amyloid beta pathology.
Extracellular vesicles of the blood-brain barrier: Role in the HIV-1 associated amyloid beta pathology.
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DOI：
10.1016/j.mcn.2016.12.006
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Toborek M
中科院分区：
文献类型：
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作者：
András IE;Leda A;Contreras MG;Bertrand L;Park M;Skowronska M;Toborek M
感染艾滋病毒的大脑的特点是β淀粉样蛋白（Aβ）沉积增加。据信，血脑屏障 (BBB) 对于 Aβ 稳态至关重要，并有助于 Aβ 在大脑中的积累。细胞外囊泡 (ECV) 与外泌体一样，最近因其在 Aβ 病理学中发挥重要作用而受到广泛关注。此外，HIV-1 劫持了外泌体的出芽和释放途径。因此，我们研究了 BBB 衍生的 ECV 在 HIV-1 诱导的大脑 Aβ 病理学中的参与情况。我们的结果表明，与对照组相比，HIV-1 增加了脑内皮细胞的 ECV 释放，并提高了其 Aβ 含量。有趣的是，脑内皮细胞来源的 ECV 将 Aβ 转移到星形胶质细胞和周细胞。将携带荧光 Aβ 的脑内皮 ECV 输注到小鼠的颈内动脉中，导致与脑微血管和脑实质相关的 Aβ 荧光。这些结果表明携带 Aβ 的 ECV 可以成功地穿过 BBB 转移到大脑中。基于这些观察，我们得出结论，HIV-1 促进携带 Aβ 的脑内皮细胞 ECV 的脱落；这一过程可能会增加神经血管单元细胞的 Aβ 暴露，并导致 HIV 感染大脑中淀粉样蛋白的沉积。
HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aβ pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Aβ cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred Aβ to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent Aβ into the internal carotid artery of mice resulted in Aβ fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying Aβ can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying Aβ; a process that may increase Aβ exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.