SIMILARITIES IN THE AGE-RELATED HIPPOCAMPAL DEPOSITION OF PERIODIC ACID-SCHIFF-POSITIVE GRANULES IN THE SENESCENCE-ACCELERATED MOUSE P8 ANDC57BL 6 MOUSE STRAINS/
H. Kuo et al., SIMILARITIES IN THE AGE-RELATED HIPPOCAMPAL DEPOSITION OF PERIODIC ACID-SCHIFF-POSITIVE GRANULES IN THE SENESCENCE-ACCELERATED MOUSE P8 ANDC57BL 6 MOUSE STRAINS/, Neuroscience, 74(3), 1996, pp. 733-740
With advancing age, clusters of abnormal granules positive for periodi
c acid-Schiff appear in the hippocampus bf C57BL/6 (B6) mice and the s
enescence-accelerated mouse (SAM) P8. The granules can also be visuali
zed with a polyclonal antibody to a 110,000 mol. wt laminin-binding pr
otein and stain specifically with a monoclonal antibody to heparan sul
fate proteoglycan. The present study used light- and electron-microsco
pic analysis to compare the staining and morphological properties of t
hese granules in SAM P8 hippocampus with those in B6 hippocampus at di
fferent ages. The results of the light-microscopic analysis revealed t
hat granules in SAM P8 and B6 had similar morphology, staining charact
eristics and distribution patterns, and appeared to have a close assoc
iation 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 sim
ilar 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 succe
ssive ultrastructural changes from the exterior to interior of the gra
nules suggest that the degenerative process was initiated outside the
granules and that degenerative structures migrate inward. Astrocytes a
nd heparan sulfate proteoglycan are closely associated with beta-amylo
id deposits in Alzheimer's disease. The presence of astrocyte-associat
ed heparan sulfate proteoglycan-positive material in aged SAM P8 and B
6 mice might model age-related alterations in glia function possibly i
nvolved in human cerebral amyloidogenesis.