Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure.
Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure.
复制标题
DOI：
10.1016/j.toxlet.2012.07.002
复制
发表时间：
2012-09-03
影响因子：
3.5
通讯作者：
Zheng, Wei
中科院分区：
文献类型：
--
作者：
Gu, Huiying;Robison, Gregory;Hong, Lan;Barrea, Raul;Wei, Xing;Farlow, Martin R.;Pushkar, Yulia N.;Du, Yansheng;Zheng, Wei
关键词：
先前对人类和动物的研究表明，铅（Pb）暴露与阿尔茨海默病（AD）病因之间可能存在关联。急性暴露于铅的动物表现出淀粉样蛋白前体蛋白（APP）的过度表达，并随后在脑细胞外空间积累β -淀粉样蛋白（Aβ）。本研究旨在探讨体内铅暴露是否会增加脑内Aβ浓度，从而导致脑组织淀粉样斑块沉积。2-3月龄遗传过表达淀粉样斑块的人Tg-SWDI APP转基因小鼠，每天1次口服50 mg/kg醋酸铅，持续6周；同一小鼠品系的对照组给予相同的醋酸钠摩尔浓度。ELISA结果显示大鼠脑脊液、脑皮层和海马中a β明显升高。免疫组织化学显示暴露于铅的动物大脑中可检测到淀粉样斑块的增加。Morris水迷宫神经行为测试显示，铅处理小鼠的空间学习能力受损，而C57BL/6野生型小鼠的空间学习能力没有受损。体外研究进一步发现Pb促进了Aβ纤维的形成。此外，同步x射线荧光研究表明，体内暴露于铅的小鼠淀粉样斑块中存在高水平的铅。综上所述，这些数据表明，铅暴露与随后小鼠大脑中Aβ水平升高似乎与淀粉样斑块的形成有关。铅明显促进Aβ纤维的形成并参与淀粉样斑块的沉积。
Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer’s disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (Aβ) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of Aβ, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50 mg/kg Pb acetate once daily for 6 wk; a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of Aβ in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated Aβ fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated Aβ level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates Aβ fibril formation and participates in deposition of amyloid plaques.
登录
查看更多内容
影响因子：
10.4
作者：
通讯作者：
--
影响因子：
3.5
作者：
Jiang, Yue-Ming;Long, Li-Ling;Zhu, Xia-Yan;Zheng, Hong;Fu, Xue;Ou, Shi-Yan;Wei, Dong-Lu;Zhou, Hai-Lin;Zheng, Wei
通讯作者：
Zheng, Wei
影响因子：
2.9
作者：
Moreira, EG;Vassilieff, I;Vassilieff, VS
通讯作者：
Vassilieff, VS
影响因子：
4.8
作者：
Davis, J;Xu, F;Van Nostrand, WE
通讯作者：
Van Nostrand, WE
影响因子：
5.7
作者：
Leskovjan, Andreana C.;Lanzirotti, Antonio;Miller, Lisa M.
通讯作者：
Miller, Lisa M.