Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain.
Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain.
复制标题
Slit2的过度表达可改善衰老小鼠大脑中血管旁通路的功能
DOI：
10.3892/ijmm.2018.3802
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发表时间：
2018-10
影响因子：
5.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li G;He X;Li H;Wu Y;Guan Y;Liu S;Jia H;Li Y;Wang L;Huang R;Pei Z;Lan Y;Zhang Y
衰老与星形胶质细胞激活和水通道蛋白-4 （AQP4）水通道去极化引起的血管旁通路损伤有关，导致包括淀粉样蛋白β (Aβ)在内的蛋白质废物在脑实质中积累。分泌糖蛋白狭缝引导配体2 （Slit2）在调节中枢神经系统功能和炎症反应过程中起重要作用。本研究采用15月龄的Slit2过表达转基因小鼠（Slit2- tg小鼠）和双光子荧光显微镜来评估血管旁通路的动态清除和血脑屏障（BBB）的完整性。用免疫荧光法观察星形胶质细胞的反应性、AQP4的极性和脑实质中Aβ的沉积。采用Morris水迷宫实验研究Slit2对衰老小鼠空间记忆认知的影响。研究发现，Slit2过表达通过抑制星形细胞活化和维持星形细胞终足AQP4极性，提高了Slit2- tg小鼠血管旁通路的清除。此外，Slit2还恢复了老化引起的血脑屏障破坏。Slit2-Tg小鼠脑内Aβ积累明显减少。此外，水迷宫实验表明，Slit2改善了衰老小鼠的空间记忆认知。这些结果表明，Slit2可能具有用于预防和治疗老年人神经退行性疾病的潜力。
Aging is associated with impairment of the paravascular pathway caused by the activation of astrocytes and depolarization of protein aquaporin-4 (AQP4) water channels, resulting in the accumulation of protein waste, including amyloid β (Aβ), in the brain parenchyma. The secreted glycoprotein slit guidance ligand 2 (Slit2) is important in regulating the function of the central nervous system and inflammatory response process. In the present study, 15-month-old Slit2 overexpression transgenic mice (Slit2-Tg mice) and two-photon fluorescence microscopy were used to evaluate the dynamic clearance of the paravascular pathway and the integrity of the blood-brain barrier (BBB). The reactivity of astrocytes, polarity of AQP4 and deposition of Aβ in the brain parenchyma were analyzed by immunofluorescence. A Morris water maze test was used to examine the effect of Slit2 on spatial memory cognition in aging mice. It was found that the overexpression of Slit2 improved the clearance of the paravascular pathway by inhibiting astrocyte activation and maintaining AQP4 polarity on the astrocytic endfeet in Slit2-Tg mice. In addition, Slit2 restored the disruption of the BBB caused by aging. The accumulation of Aβ was significantly reduced in the brain of Slit2-Tg mice. Furthermore, the water maze experiment showed that Slit2 improved spatial memory cognition in the aging mice. These results indicated that Slit2 may have the potential to be used in the prevention and treatment of neurodegenerative diseases in the elderly.
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影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
影响因子：
3.2
作者：
London NR;Li DY
通讯作者：
Li DY
甲状腺蛛网膜下腔出血后独立于糖控制后，阵发途径会导致血管炎和神经炎症。
影响因子：
9
作者：
Luo C;Yao X;Li J;He B;Liu Q;Ren H;Liang F;Li M;Lin H;Peng J;Yuan TF;Pei Z;Su H
通讯作者：
Su H
影响因子：
21.3
作者：
Jones CA;Nishiya N;London NR;Zhu W;Sorensen LK;Chan AC;Lim CJ;Chen H;Zhang Q;Schultz PG;Hayallah AM;Thomas KR;Famulok M;Zhang K;Ginsberg MH;Li DY
通讯作者：
Li DY
影响因子：
6.2
作者：
Hagino, S;Iseki, K;Wanaka, A
通讯作者：
Wanaka, A