Similarities in the age-related hippocampal deposition of periodic acid-Schiff-positive granules in the senescence-accelerated mouse P8 and C57BL/6 mouse strains
Similarities in the age-related hippocampal deposition of periodic acid-Schiff-positive granules in the senescence-accelerated mouse P8 and C57BL/6 mouse strains
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DOI：
10.1016/0306-4522(96)00169-8
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发表时间：
1996-10-01
期刊：
影响因子：
3.3
通讯作者：
Jucker, M
中科院分区：
文献类型：
--
作者：
Kuo, H;Ingram, DK;Jucker, M
随着年龄的增长，在C57 BL/6（B6）小鼠和加速衰老小鼠（SAM）P8的海马中出现了高碘酸-希夫阳性的异常颗粒簇。颗粒也可以用110，000 mol. WT层粘连蛋白结合蛋白，并用硫酸乙酰肝素蛋白聚糖的单克隆抗体特异性染色。本研究采用光镜和电镜技术，比较了不同年龄SAM P8和B6海马中这些颗粒的染色和形态学特征。光镜分析结果显示，SAM P8和B6中的颗粒具有相似的形态、染色特征和分布模式，并与星形胶质细胞突起有密切联系。SAM P8小鼠（2 - 3月龄）颗粒的出现早于B6小鼠（4 - 6月龄），但两种品系的最大发生率相似。电镜分析表明，SAM P8和B6小鼠的颗粒也具有非常相似的超微结构。两种菌株中的颗粒被不连续的膜所包围，并且主要含有晶体样的退化物质。从颗粒外部到内部的连续超微结构变化表明，变性过程是在颗粒外部开始的，变性结构向内迁移。星形胶质细胞和硫酸乙酰肝素蛋白多糖与阿尔茨海默病中的β-淀粉样蛋白沉积密切相关。在老年SAM P8和B6小鼠中存在星形胶质细胞相关硫酸乙酰肝素蛋白多糖阳性物质可能是与人脑淀粉样蛋白生成有关的胶质细胞功能年龄相关改变的模型。
With advancing age, clusters of abnormal granules positive for periodic acid-Schiff appear in the hippocampus bf C57BL/6 (B6) mice and the senescence-accelerated mouse (SAM) P8. The granules can also be visualized with a polyclonal antibody to a 110,000 mol. wt laminin-binding protein and stain specifically with a monoclonal antibody to heparan sulfate proteoglycan. The present study used light- and electron-microscopic analysis to compare the staining and morphological properties of these granules in SAM P8 hippocampus with those in B6 hippocampus at different ages. The results of the light-microscopic analysis revealed that granules in SAM P8 and B6 had similar morphology, staining characteristics and distribution patterns, and appeared to have a close association with astrocytic processes. The onset of granules in SAM P8 mice (at two to three months of age) was earlier than that observed in B6 mice (al four to six months of age), but the maximum incidence was similar in both strains. Electron-microscopic analysis revealed that the granules in SAM P8 and B6 mice also had a very similar ultrastructure. Granules in both strains were surrounded by a discontinuous membrane and contained mostly crystalline-like, degenerated material. The successive ultrastructural changes from the exterior to interior of the granules suggest that the degenerative process was initiated outside the granules and that degenerative structures migrate inward.Astrocytes and heparan sulfate proteoglycan are closely associated with beta-amyloid deposits in Alzheimer's disease. The presence of astrocyte-associated heparan sulfate proteoglycan-positive material in aged SAM P8 and B6 mice might model age-related alterations in glia function possibly involved in human cerebral amyloidogenesis.