Prior exposure to repeated peripheral LPS injections prevents further accumulation of hippocampal beta-amyloid

• Published in: Brain, behavior, and immunity Vol. 66; pp. e12 - e13
• Main Authors: White, J.D., Peterman, J.L., Hardy, A., Eimerbrink, M.J., Paulhus, K.C., Thompson, M.A., Chumley, M.J., Boehm, G.W.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2017
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2017.07.056

Alzheimer’s disease (AD) is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles. Our laboratory has previously demonstrated that repeated bouts of LPS-induced inflammation increase beta-amyloid within the hippocampus of non-transgenic mice. Given the relationship between inflammation and AD pathology onset and progression, we sought to explore how a second series of peripheral lipopolysaccharide (LPS) would impact beta-amyloid levels. Male C57BL6/J mice were given daily injections of LPS (250μg/kg) or sterile saline for seven days. Fourteen days following the last injection, animals were administered another series of daily injections of LPS or sterile saline. Hippocampal tissue was collected and assayed to quantify total beta-amyloid levels. Results demonstrated that animals given one round of LPS injections had significantly more beta-amyloid than saline injected controls, whereas animals administered two rounds of LPS had intermediary levels of beta-amyloid. This effect appears to be driven by the reduced inflammatory response to the secondary exposure to LPS following a fourteen-day recovery. More specifically, four hours following the first LPS injection of the second series, animals previously exposed to LPS produced significantly less pro-inflammatory cytokine mRNA than animals exposed to LPS for the first time. The mechanisms behind this diminished inflammatory response may be related to antibody production against LPS or cellular tolerance, both of which are currently being explored.