APPSWE Tg2576小鼠脑屏障结构

崔占军 刘芳 赵凯冰 李冰梅 刘中华*

doi:10.16098/j.issn.0529-1356.2018.05.002

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解剖学报 ›› 2018, Vol. 49 ›› Issue (5) : 571-578. DOI: 10.16098/j.issn.0529-1356.2018.05.002

神经生物学

APPSWE Tg2576小鼠脑屏障结构

崔占军¹ 刘芳²赵凯冰³ 李冰梅⁴ 刘中华^1*

作者信息 +

Brain barrier structure of APPSWE Tg2576 mice

CUI Zhan-jun¹ LIU Fang² ZHAO Kai-bing³ LI Bing-mei⁴ LIU Zhong-hua ^1*

Author information +

文章历史 +

摘要

目的探讨小鼠的血脑屏障（BBB）及血脑脊液屏障（BCSFB）的基本结构及其在阿尔茨海默病（AD）发生、发展过程中结构、功能及及其超微结构的改变。方法实验用动物采用APPSWE Tg2576鼠，分为APPSWE转基因阳性鼠（模型组）和同窝生野生型小鼠（对照组），每组各20只。饲养16个月后进行全身灌流固定, 开颅切取侧脑室室壁及其脉络丛组织。采用免疫荧光及透射电子显微镜技术观察BBB及BCSFB的超微结构，从而观察AD模型脑屏障的改变。结果 AD模型组与对照组相比较，血管密度明显降低；AD小鼠脑屏障正常结构受到损害，主要是脑血管内皮细胞（或脉络丛内皮细胞）之间的连接及其细胞器受损，脉络丛超微结构也出现明显变化，主要表现为细胞间隙增宽，细胞之间的黏附连接等连接结构也有部分碰坏，胞质内出现较多的囊泡状结构等。结论和正常鼠相比，AD鼠脑屏障受到一定的损害，可能致使脑屏障的转运机制出现相应的改变并影响脑内β-淀粉样蛋白（Aβ）的清除，脑屏障中存在的稳态机制，如其分泌物和受体介导的信号传导也可能出现改变，这些因素可能共同参与了AD的形成和进展。

Abstract

Objective To investigate the basic structure of the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSFB) in mice and their changes in structure, function, and ultrastructure during the development and progression of AD. Methods The APPSWE Tg2576 mice were used and divided into APPSWE transgenic positive mice (model group) and littermates wild type mice (control group), twety mice in each group. After 16 months of feeding, whole body perfusion was performed and the craniotomy was performed to obtain the lateral ventricle wall and its choroid plexus. Immunofluorescence and transmission electron microscopy were used to observe the ultrastructure of BBB and BCSFB, so as to observe the changes of brain barrier of AD model. Results The vascular density was significantly lower in the AD model group than in the control group; the normal structure of the brain barrier in AD mice was impaired, mainly due to the connection between the brain vascular endothelial cells (or choroid plexus endothelial cells) and their organelles being damaged. The ultrastructure of the choroid plexus also showed significant changes. The main manifestations were the widening of the intercellular space, and some of the connecting structures between the cells, such as adhesion and connection, and some vesicle-like structures in the cytoplasm. Conclusion Compared with normal mice, the brain barrier of AD rats is damaged, which may lead to corresponding changes in the brain barrier transport mechanism and affect the clearance of Aβ in the brain, and the steady-state mechanisms existing in the brain barrier, such as secretions and receptors thereof. Mediated signaling may also change, and these factors may be involved in the formation and progression of AD.

导出引用

崔占军刘芳赵凯冰李冰梅刘中华. APPSWE Tg2576小鼠脑屏障结构[J]. 解剖学报. 2018, 49(5): 571-578 https://doi.org/10.16098/j.issn.0529-1356.2018.05.002

CUI Zhan-jun LIU Fang ZHAO Kai-bing LI Bing-mei LIU Zhong-hua. Brain barrier structure of APPSWE Tg2576 mice[J]. Acta Anatomica Sinica. 2018, 49(5): 571-578 https://doi.org/10.16098/j.issn.0529-1356.2018.05.002

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