Insufficient resolution response in the hippocampus of a senescence-accelerated mouse model--SAMP8.

Aging is the primary risk factor for Alzheimer's disease (AD), and it is known that inflammation is associated with both aging and AD. To resolve inflammation, biosynthesis of the specialized pro-resolving mediators (SPMs) is enhanced in a programmed and active manner. We investigated the effect of age on resolution by analyzing hippocampal tissue from 2- and 9-month-old senescence-accelerated mouse prone 8 (SAMP8), as well as age-matched senescence-accelerated mouse resistant 1 (SAMR1). Pro-inflammatory markers increased upon age in SAMP8 mice and were also higher than those in age-matched SAMR1 mice. However, neither SPMs nor their receptors were enhanced upon age in SAMP8 mice compared to age-matched SAMR1 mice. Analysis of SPM biosynthetic enzymes revealed elevated levels of leukocyte type 12-lipoxygenase (L12-LOX) and decreased 5-LOX levels upon age in SAMR1 mice, whereas they remained unchanged in SAMP8 mice. Moreover, we found partial co-localization of L12-LOX and amyloid beta (Aβ) staining, as well as correlation between L12-LOX and phosphorylated tau levels in SAMP8, but not SAMR1 mice. Thus, we conclude that the resolution response in SAMP8 mice is insufficient to counteract the increased inflammation with age, and this may have a role in the development of AD-like pathologies.