Abstract

In this study, in order to examine morphological events related to the age-related increase of the brain accumulation of serum albumin, an immunocytochemical study of the blood–brain barrier (BBB) to endogenous albumin and ultrastructural studies of the BBB to blood-borne horseradish peroxidase (HRP) were performed in several brain regions of SAMP8 and SAMR1 (control) mice. Some venules in the olfactory bulb showed clear leakage of albumin in aged SAMP8 and the percentage of capillaries showing leakage of albumin was significantly larger in SAMP8 than in SAMR1 mice. Ultrastructural examination in the hippocampus showed that staining for HRP spread diffusely throughout the parajunctional cytoplasm of the endothelial cells in aged SAMP8 mice, but not in young SAMP8 or in SAMR1 mice. In addition, undulated endothelial cell surface with microvillous protrusions, membranous inclusions within the basal lamina, and swelling of perivascular astroglial endofeet were occasionally seen in several brain regions in SAMP8 mice, while these ultrastructural findings were hardly observed in SAMR1 brains. These findings indicate that the BBB function deteriorated with aging in the olfactory bulb and hippocampus of SAMP8 mice. The deteriorated BBB function may promote age-related deficits in learning and memory in SAMP8 mice.

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