Microglial P2X7 receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease

Microglial P2X7 receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease
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DOI:
10.3858/emm.2011.43.1.001
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发表时间:
2011-01-31
影响因子:
12.8
通讯作者:
Lee, Yong Beom
Lee, Yong Beom
中科院分区:
医学2区
文献类型:
--
作者:
Lee, Hwan Goo;Won, Sun Mi;Lee, Yong Beom

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在阿尔茨海默病(AD)的APP(swe)/PS1 dE 9小鼠模型中,研究了小胶质细胞中P2 X(7)受体(P2 X(7)R)表达通过活性氧(ROS)产生介导神经元损伤的可能性。P2 X(7)R主要表达于A β斑块形成前3个月龄的CD 11b免疫阳性小胶质细胞。此外,在6月龄动物的P2 X(7)R阳性小胶质细胞中检测到NADPH氧化酶的催化亚基gp 91(phox)和乙锭荧光,表明P2 X(7)R阳性小胶质细胞可以产生ROS。突触后密度95阳性树突在6月龄小鼠大脑皮层中P2 X(7)R阳性区域显示出明显的损伤。总之,P2 X(7)R激活和小胶质细胞中ROS产生的上调与A β增加平行,并与AD中的突触毒性相关。
The possibility that P2X(7) receptor (P2X(7)R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APP(swe)/PS1dE9 mouse model of Alzheimer's disease (AD). P2X(7)R was predominantly expressed in CD11b-immunopositive rnicroglia from 3 months of age before A beta plaque formation. In addition, gp91(phox), a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X(7)R-positive microglial cells of animals at 6 months of age, indicating that P2X(7)R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X(7)R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X(7)R activation and ROS production in microglia are parallel with A beta increase and correlate with synaptotoxicity in AD.