Jucker M, Walker L C, Schwarb P, Hengemihle J, Kuo H, Snow A D, Bamert F, Ingram D K
Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland.
Neuroscience. 1994 Jun;60(4):875-89. doi: 10.1016/0306-4522(94)90269-0.
With advancing age, clusters of unusual granules appear in the brains of C57BL/6 (B6) mice. At the light, confocal laser and electron microscopic levels, the granules represent aggregations of fibrillar material often associated with astrocytes. The fibrillar material is largely free of normal organelles and has been located within astrocytic somata and processes, although in many cases the material is found in the neuropil and is surrounded by a discontinuous membrane. The deposits occur predominantly in hippocampus, but also in piriform cortex, cerebellum and less frequently in some other brain regions. They become evident about six months of age and increase markedly in both number and size thereafter. Incidence of the deposits varies greatly among inbred mouse strains. At six to 12 months of age, granules are abundant in male and female B6, and are absent in BALB/c, CBA, DBA/2 and A mice. In hybrid strains with a B6 background the deposits are also present and thus appear to manifest dominant genetic heritability. Similar granular structures have been described in adult brains of the senescence accelerated mouse and have been noted, albeit very rarely, in aged mice from other strains. While immunostaining of the granules with several polyclonal antisera was found by preabsorption with antigens to be non-specific, immunolabeling with monoclonal antibodies to heparan sulfate proteoglycan core protein and to laminin suggest these or related molecules as components of the fibrillar material. The presence of glycosaminoglycans is supported by staining with periodic acid-Schiff and Gomori's methenamine silver methods. The functional significance of the murine deposits is not yet clear. The deposits do not represent senile plaques with beta-amyloid deposition, but they might mimic the deposition of extracellular matrix molecules that is hypothesized to be a precursor condition for plaque formation and cerebral amyloidosis. Furthermore, the genetic differences in the incidence of the fibrillar deposits has potential to model aspects of familial neurodegenerative diseases.
随着年龄的增长，C57BL/6（B6）小鼠的大脑中会出现异常颗粒簇。在光学显微镜、共聚焦激光显微镜和电子显微镜水平下，这些颗粒代表了通常与星形胶质细胞相关的纤维状物质聚集体。纤维状物质基本不含正常细胞器，位于星形胶质细胞的胞体和突起内，不过在许多情况下，该物质存在于神经毡中并被不连续的膜所包围。这些沉积物主要出现在海马体中，但也存在于梨状皮质、小脑，在其他一些脑区出现的频率较低。它们在约6个月大时变得明显，此后数量和大小都显著增加。不同近交系小鼠中这些沉积物的发生率差异很大。在6至12个月大时，雄性和雌性B6小鼠中颗粒丰富，而BALB/c、CBA、DBA/2和A小鼠中则没有。在具有B6背景的杂交品系中也存在这些沉积物，因此似乎表现出显性遗传遗传性。在衰老加速小鼠的成年大脑中也描述过类似的颗粒结构，并且在来自其他品系的老年小鼠中也有发现，尽管非常罕见。虽然用几种多克隆抗血清对颗粒进行免疫染色经抗原预吸附后发现是非特异性的，但用抗硫酸乙酰肝素蛋白聚糖核心蛋白和层粘连蛋白的单克隆抗体进行免疫标记表明这些分子或相关分子是纤维状物质的成分。高碘酸-希夫染色和Gomori六胺银法染色证实了糖胺聚糖的存在。小鼠沉积物的功能意义尚不清楚。这些沉积物并不代表有β-淀粉样蛋白沉积的老年斑，但它们可能模拟细胞外基质分子的沉积，据推测这是斑块形成和脑淀粉样变性的前期状况。此外，纤维状沉积物发生率的遗传差异有可能为家族性神经退行性疾病的某些方面提供模型。
