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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. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The nervous, endocrine and immune systems are functionally interconnected so that they may form a complex metasystem. Abnormalities within the neuroendocrine compartment can thus affect immune mechanisms and vice versa. The Lurcher-type mutation in mice has a profound impact on brain development in both homozygous and heterozygous individuals, which is followed by immune system changes. We investigated whether macroscopic changes in the thymus size were associated with an altered thymocyte development or with changes in peripheral T cell subset distribution. Methods: CD3, CD4 and CD8 expressions on thymocytes and peripheral T cells were compared with those in wild-type and Lurcher heterozygous C3H mice using surface immunophenotyping and flow cytometry. Galanthus nivalis agglutinin binding to thymocytes was measured at the same time. Results: While no differences between experimental groups were observed in 1-month-old mice, a critical reduction of numbers of thymocytes and namely double-positive cells occurred before the age of 3 months in Lurcher mice, which was accompanied by thymus involution. Interestingly, this was not accompanied by significant differences in major T subset proportions in the peripheral lymphatic tissue. Conclusions: We interpret our observations as hallmarks of premature thymus ageing in heterozygous Lurcher mice with only a marginal effect in the periphery in early adulthood. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]