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A novel phospholipid-based drug formulation, VP025, modulates age- and LPS-induced microglial activity in the rat
Darren S D Martin1, Michelle Walsh, Anne-Marie Miller
1Vasogen Ireland Ltd., Trinity College Institute of Neuroscience, Physiology Department, Trinity College, Dublin, Ireland.
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-1beta (IL-1beta) 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-gamma 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-1beta concentration were increased, and CD200 expression was reduced, in the hippocampus of these rats. VP025 reversed changes in CD40, IL-1beta 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.
Insights
VP025, a novel nanoparticle, reduces inflammation in aged and LPS-treated rats by modulating macrophages, microglia, and neurons. This treatment restored long-term potentiation, suggesting therapeutic potential for age-related cognitive decline.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Aging central nervous system exhibits increased microglial inflammation and interleukin-1beta (IL-1beta) in the hippocampus.
- This neuroinflammation is associated with impaired long-term potentiation, a key mechanism for memory formation.
Purpose of the Study:
- To evaluate the anti-inflammatory effects of VP025, a phosphatidylglycerol-containing phospholipid nanoparticle, on the hippocampus of aged and lipopolysaccharide (LPS)-treated rats.
Main Methods:
- VP025's impact on macrophages and microglia was assessed in LPS-treated rats.
- Hippocampal inflammatory markers, including MHC II mRNA, CD40, IL-1beta, and CD200 expression, were analyzed.
- Long-term potentiation was measured in aged and LPS-treated rats.
Main Results:
- VP025 modulated macrophage activity, reducing IFN-gamma in LPS-treated rats.
- In the hippocampus, VP025 reversed increased CD40, IL-1beta, and decreased CD200 expression in aged rats.
- VP025 restored long-term potentiation in both aged and LPS-treated rats.
Conclusions:
- VP025 demonstrates the capacity to modulate macrophage, microglia, and neuronal activity.
- These findings suggest VP025 as a potential therapeutic agent for age-related neuroinflammation and cognitive dysfunction.