ASTROGLIAL CONNEXIN IMMUNOREACTIVITY IS SPECIFICALLY ALTERED AT β-AMYLOID PLAQUES IN β-AMYLOID PRECURSOR PROTEIN/PRESENILIN1 MICE
ASTROGLIAL CONNEXIN IMMUNOREACTIVITY IS SPECIFICALLY ALTERED AT β-AMYLOID PLAQUES IN β-AMYLOID PRECURSOR PROTEIN/PRESENILIN1 MICE
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DOI：
10.1016/j.neuroscience.2010.08.001
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发表时间：
2010-11-24
期刊：
影响因子：
3.3
通讯作者：
Koulakoff, A.
中科院分区：
文献类型：
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作者：
Mei, X.;Ezan, P.;Koulakoff, A.
淀粉样斑块周围星形胶质细胞的活化是阿尔茨海默病（AD）的标志，其后果尚不清楚。星形胶质细胞的特征在于由两种间隙连接形成蛋白，连接蛋白-43和30介导的高水平的细胞间通讯。由于星形胶质细胞连接蛋白（Cxs）参与神经元功能障碍和死亡，我们分析了其表达模式在两个小鼠模型的AD，即两个不同的β-淀粉样前体蛋白（APP）/早老素1（PS1）小鼠，使用蛋白质印迹和免疫组织化学共聚焦显微镜分析。在2个月大的年轻小鼠中，在β-淀粉样蛋白（A β）沉积物出现之前，两种Cx的分布与对照小鼠相似。在>= 4个月的老年动物中，在致密核心A β斑块的微环境中观察到连接蛋白免疫染色模式的局部改变。在大多数斑块中，检测到两个Cx的免疫反应性升高，这有助于在18月龄APP/PS1小鼠中检测到的连接蛋白表达的总体增加。激活的小胶质细胞并没有导致连接蛋白免疫反应性的升高，连接蛋白免疫反应性集中在浸润斑块的星形胶质细胞过程中。在一小部分斑块中（
Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer disease (AD) with consequences yet poorly understood. Astrocytes are characterized by a high level of intercellular communication mediated by two gap-junction forming proteins, connexin-43 and connexin-30. As astroglial connexins (Cxs) are involved in neuronal dysfunctions and death, we have analyzed their expression pattern in two murine models of AD, that is two different beta-amyloid precursor protein (APP)/presenilin1(PS1) mice, using western blot and immunohistochemistry analyzed in confocal microscopy. In young mice at 2 months, before the emergence of beta-amyloid (A beta) deposits, the distribution of both Cxs was similar to that of control mice. In older animals >= 4 months, local modifications in connexin immunostaining pattern were observed in the microenvironment of dense core A beta plaques. In a majority of plaques, an elevated immunoreactivity was detected for both Cxs contributing to the overall increase in connexin expression detected in 18 month old APP/PS1 mice. Activated microglial cells did not contribute to the elevated connexin immunoreactivity that was concentrated in astroglial processes infiltrating the plaques. In a small proportion of plaques (