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 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.
Jucker
M
M
Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland.
Walker
L C
LC
Schwarb
P
P
Hengemihle
J
J
Kuo
H
H
Snow
A D
AD
Bamert
F
F
Ingram
D K
DK
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism*; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D013045:Species Specificity