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Senescence-accelerated mouse(SAM), a murine model of accelerated senescence, has been established by Takeda et al. SAM consists of senescence-accelerated-prone mouse(SAMP) and senescence-accelerated-resistant mouse(SAMR), the latter of which shows normal aging characteristics. In murine senile amyloidosis, apolipoprotein A-II (apoA-II), a major constituent of serum high density lipoprotein (HDL) is deposited in the form of amyloid fibrils. Sequence analysis of apoA-II in SAMP1 and SAMR1 revealed an amino acid substitution at position 5, i.e. glutamine (Gln) in SAMP1 and proline (pro) in SAMR1. In SAMP1, the senescence process is accelerated and senile amyloidosis is evident, while in SAMR1, there is a normal aging process and little evidence of senile amyloidosis. Among the P-series, it is found that SAMP8 mice show significant impairments in various learning tasks compared with SAMR1. Further studies suggest that characteristics of age-related deficits in learning and memory, changes in emotional behavior and disorder of circadian rhythms in SAMP8 are described. Body weights began to decrease about 11 months in SAMP1 and 16 months in SAMRl, and were higher in SAMR1 than in SAMP1. Organ weights such SS heart, kidney, brain and liver were significantly lower in SAMP8 than in SAMR1. Interestingly, calcium levels in heart, liver and skeletal muscle were remarkably lower in SAMP8 than in SAMR1. Serum triglyceride levels were higher in SAMP1 than in SAMR1, while serum cholesterol and phospholipid levels were significantly lower in SAMPl than in SAMRl. VLDL and LDL. cholesterol levels in serum were remarkably higher in SAMPl than in SAMRl, while serum HDL-cholesterol levels were significantly lower in SAMPl than in SAMRl. At young mice, cholesterol levels of brain membranes in SAMP1 were significantly higher than those in SAMR1. HDL apolipoproteins in SAMRl and SAMPl mice are reported to consist of apoA-l, apoA-ll and apoC. ApoA-I increased with advancing age in both SAMRl and sAMP1 strains, and was very high in SAMPl with severe amyloid deposition. An age-related decrease in plasma apoA-II levels was observed in both SAMRl and SAMP1 strains; plasma apoA-ll levels in SAMP1 mice with severe amyloid deposition was markedly decreased compared with these in SAMRl mice. These findings suggest that the marked decrease of plasm. apoA-ll in SAMP1 is due to its decrease in the HDL fraction. The yields of brain membranes and ratios of 20:4/ l8:2 in SAMP1 gradually decreased with age, but these ratios in brain microsomes were significantly higher in SAMP1 than in SAMR1, indicating these results may be accelerated to lipid peroxide levels in SAMP1. Malondialdehyde and hydroxyl radical in brain of SAMP1 decreased with age, whereas those levels in microsomes of brain were remarkably higher in SAMP1 than in SAMRl. It suggests that malfunction and aging process were more rapidly accelerated in SAMPl compared with SAMRl, Amyloid β/A4 protein deposition seen in subjects with Alzheimer’s disease has been found only in higher mammalians such as primates, dogs etc, Numerical densities of the β/A4-like immunoreactive granular structures (β,LlGS) increase significantly with advancing age in brain of SAMR1 and SAMP8 mice, but increases in numerical densities of β,LlGS are significantly more marked in SAMP8 compares with SAMRl, These results suggest that SAMP8 significantly exhibits age-related deterioration of learning and memory abilities compared with SAMR1 in normal characteristic of aging.
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