Background: A common change that occurs with age in the central nervous system is an increase in microglial-associated inflammation. This is usually coupled with an increase in the concentration of the inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus and an inhibition in long-term potentiation. Objectives: To assess the effects of a novel preparation of phospholipid nanoparticles incorporating phosphatidylglycerol, VP025, on inflammatory changes in hippocampus of aged and lipopolysaccharide (LPS)-treated rats. Methods/Results: We report that a possible initial target cell of the putative anti-inflammatory actions of VP025 may be macrophages, as VP025 is engulfed by, and has the capacity to alter the activity of, these cells. VP025 reversed the increase in IFN-γ concentration in supernatant taken from peritoneal macrophages harvested from LPS-treated rats. In addition, markers of microglial activity, major histocompatibility complex class II (MHC II) mRNA expression, CD40 expression and IL-1β concentration were increased, and CD200 expression was reduced, in the hippocampus of these rats. VP025 reversed changes in CD40, IL-1β and CD200 in aged rats, and also restored long-term potentiation in aged and LPS-treated rats. Conclusions: We conclude that VP025 has the ability to modulate the activity of macrophage, microglia and neurons in response to stressors such as ageing and LPS treatment.

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