Senescence-accelerated overexpression of S100beta in brain of SAMP6 mice.

S100beta is an astrocyte-derived protein with paracrine and autocrine effects on neurons and glia. Brain S100beta expression increases progressively with age, and this increased expression has been implicated as a factor underlying the increasing risk of Alzheimer's disease that accompanies aging. Senescence acceleration-prone (SAMP) mice are a group of inbred strains that provide animal models of aging and of various age-related disease processes in the brain and peripheral tissues. One of these strains, the osteopenic SAMP6, has not been previously associated with central nervous system alterations. We used Northern and Western immunoblot analysis and immunohistochemical labeling to examine S100beta expression in brains of SAMP6 mice. Cerebral tissue levels of S100beta and of S100beta mRNA were 2.2-fold and 1.6-fold those of senescence-resistant (control) mice at 4 months of age (p < 0.05 in each case), and were 3.7-fold and 1.9-fold those of control mice at 6 months of age (p < 0.01 in each case). In contrast, levels of glial fibrillary acidic protein (GFAP) in cerebral hemispheres were not different from those of controls. Image analysis of immunohistochemical preparations showed increased numbers and immunoreactive intensity of S100beta-immunoreactive astrocytes in both the hippocampus and cerebral cortex of SAMP6 mice at 4 months of age (p < 0.05 or better in each case). These increases were greater in the hippocampus than in the cerebral cortex. In contrast, increases in numbers of GFAP immunoreactive astrocytes were noted only in the hippocampus. Our finding of increased S100beta gene expression in brains of SAMP6 mice mirror age-associated increases in S100beta expression in human brain and suggest that SAMP6 may provide insights into age-associated brain alterations and diseases.