Involvement of pro-inflammatory cytokines and microglia in an age-associated neurodegeneration model, the SAMP10 mouse.

The SAMP10 mouse strain is a model of brain aging in which senescence is characterized by cerebral atrophy and neurodegeneration phenotypes. To investigate the role of neuroinflammation in the age-associated neurodegeneration of SAMP10 mice, we assessed the expression of several cytokines and chemokines in the atrophy-prone brain region of SAMP10, and control, SAMR1 mice, which show a normal aging process. We also studied morphological changes in microglia with advancing age in atrophied regions. The expression of IL-1beta and IFN-gamma mRNA was about 2-fold greater in SAMP10 mice as compared to SAMR1 mice throughout their life span. The expression of IL-6 mRNA was 2.0-fold greater in SAMP10 mice as compared to SAMR1 mice at 14 months of age, although there was no difference at 3 months of age. Fourteen-month-old mice had a 2.1-fold greater expression of TNF-alpha mRNA than 3-month-old mice in both strains. The expression of MCP-1 mRNA was greater in SAMP10 mice than SAMR1 mice, and tended to increase with advancing age. Activated microglia were rarely observed in both strains at 3 months of age. At 14 months of age, however, SAMP10 mice had a 5.6-fold greater number of activated microglia than SAMR1 mice. The aforementioned results suggest the presence of a higher pro-inflammatory status in the atrophy-prone brain region of SAMP10 mice as compared to SAMR1 mice. Neuroinflammation is a possible mechanism of age-associated neurodegeneration in SAMP10 mice.