Laboratory of Neuroanatomy, Institute of Neuroscience of Castilla and León, Valladolid University (Campus of Soria), Spain.
Exp Neurol. 2010 Jun;223(2):410-21. doi: 10.1016/j.expneurol.2009.10.013. Epub 2009 Oct 29.
The aim of this study was to investigate the interaction between beta-amyloid (Abeta) peptide and astrogliosis in early stages of Abeta toxicity. In Wistar rats, anaesthetised with equitesine, a single microinjection of Abeta1-42 oligomers was placed into the retrosplenial cortex. Control animals were injected with Abeta42-1 peptide into the corresponding regions of cerebral cortex. Immunocytochemical analysis revealed an intense Abeta immunoreactivity (IR) at the level of Abeta1-42 injection site, increasing from the first 24 h to later (72 h) time point. Control injection showed a light staining surrounding the injection site. In Abeta oligomers-treated animals, Abeta-immunopositive product also accumulates in cortical cells, particularly in frontal and temporal cortices at an early (24 h) time point. Abeta-IR structures-like diffuse aggregates forms were also observed in hippocampus and in several cortical areas, increasing from the first 24 h to later (72 h) time point. In control animals no specific staining was seen neither in cortical cells nor in structures-like diffuse aggregates forms. Injections of Abeta oligomers also induce activation of astrocytes surrounding and infiltrating the injection site. Astrocyte activation is evidenced by morphological changes and upregulation of glial fibrillary acidic protein (GFAP). By GFAP immunoblotting we detected two immunopositive protein bands, at 50 and 48 kDa molecular mass. Confocal analysis also showed that GFAP co-localized with Abeta-IR material in a time-dependent manner. In conclusion, our results indicate that astrocyte activation might have a critical role in the mechanisms of Abeta-induced neurodegeneration, and that should be further studied as possible targets for therapeutic intervention in AD.
本研究旨在探讨β淀粉样蛋白（Abeta）肽与星形胶质细胞增生在 Abeta 毒性早期阶段的相互作用。在戊巴比妥钠麻醉的 Wistar 大鼠中，将 Abeta1-42 寡聚物的单次微注射置于后扣带回皮质。对照动物被注射 Abeta42-1 肽到相应的大脑皮质区域。免疫细胞化学分析显示，Abeta1-42 注射部位的 Abeta 免疫反应性（IR）强烈增加，从最初的 24 小时到后来的（72 小时）时间点。对照注射显示出围绕注射部位的轻度染色。在 Abeta 寡聚物处理的动物中，Abeta-免疫阳性产物也在皮质细胞中积累，特别是在额叶和颞叶皮质中，在早期（24 小时）时间点。Abeta-IR 结构 - 如弥漫性聚集形式的结构也在海马体和几个皮质区域中观察到，从最初的 24 小时到后来的（72 小时）时间点增加。在对照动物中，在皮质细胞中既没有看到特异性染色，也没有观察到弥漫性聚集形式的结构。Abeta 寡聚物的注射也诱导围绕和浸润注射部位的星形胶质细胞的激活。星形胶质细胞的激活通过形态变化和神经胶质纤维酸性蛋白（GFAP）的上调来证明。通过 GFAP 免疫印迹，我们检测到两种免疫阳性蛋白带，分子量为 50 和 48 kDa。共聚焦分析还显示 GFAP 与 Abeta-IR 物质在时间依赖性方式上共定位。总之，我们的结果表明星形胶质细胞的激活可能在 Abeta 诱导的神经退行性变机制中起关键作用，并且应该进一步研究作为 AD 中治疗干预的可能靶点。
