AGE-RELATED DEPOSITION OF GLIA-ASSOCIATED FIBRILLAR MATERIAL IN BRAINS OF C57BL 6 MICE/

With advancing age, clusters of unusual granules appear in the brains of C57BL/6 (B6) mice. At the light, confocal laser and electron micros copic levels, the granules represent aggregations of fibrillar materia l often associated with astrocytes. The fibrillar material is largely free of normal organelles and has been located within astrocytic somat a and processes, although in many cases the material is found in the n europil and is surrounded by a discontinuous membrane. The deposits oc cur predominantly in hippocampus, but also in piriform cortex, cerebel lum and less frequently in some other brain regions. They become evide nt about six months of age and increase markedly in both number and si ze thereafter. Incidence of the deposits varies greatly among inbred m ouse strains. At six to 12 months of age, granules are abundant in mal e and female B6, and are absent in BALB/c, CBA, DBA/2 and A mice. In h ybrid strains with a B6 background the deposits are also present and t hus appear to manifest dominant genetic heritability. Similar granular structures have been described in adult brains of the senescence acce lerated mouse and have been noted, albeit very rarely, in aged mice fr om other strains. While immunostaining of the granules with several po lyclonal antisera was found by preabsorption with antigens to be non-s pecific, immunolabeling with monoclonal antibodies to heparan sulfate proteoglycan core protein and to laminin suggest these or related mole cules as components of the fibrillar material. The presence of glycosa minoglycans is supported by staining with periodic acid-Schiff and Gom ori's methenamine silver methods. The functional significance of the m urine deposits is not yet clear. The deposits do not represent senile plaques with beta-amyloid deposition, but they might mimic the deposit ion of extracellular matrix molecules that is hypothesized to be a pre cursor condition for plaque formation and cerebral amyloidosis. Furthe rmore, the genetic differences in the incidence of the fibrillar depos its has potential to model aspects of familial neurodegenerative disea ses.