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Published on: January 30, 2014
Effects of Microglial Cytokines on Alzheimer's Disease-Related Phenomena
Yan Ji1,2, Xiaowan Wang1,3, Colin Kalicki1
1University of Kansas Alzheimer's Disease Center, Kansas, USA.
Abstract:
Recent association studies indicate several genes highly expressed by microglia influence Alzheimer's disease (AD) risk, which suggests microglial function contributes to this disease. Here, we evaluated how one component of microglial function, cytokine release, affects AD-related phenomena. First, we used a 3-hour lipopolysaccharide (LPS) treatment to activate mouse BV2 microglial cells. Next, we removed the LPS-containing medium, added LPS-free medium, and after 6 hours collected the medium conditioned by the activated BV2 microglial cells. We then exposed human neuronal SH-SY5Y cells to the conditioned medium for 24 hours. At the end of the 24-hour exposure, we assessed amyloid-β protein precursor (AβPP), tau, apolipoprotein E (ApoE), and lipid status. The amount of AβPP was unaffected, although a slight decrease in soluble AβPPα suggested a subtle reduction in AβPP non-amyloidogenic processing occurred. Tau mRNA increased, but total and phosphorylated tau levels were unchanged. ApoE mRNA increased, while ApoE protein levels were lower. Per cell lipid droplet number decreased and lipid oxidation increased. These results show cytokine release by activated microglial cells can influence specific AD-relevant physiologies and pathologies.
Insights
Activated microglia release cytokines that impact Alzheimer's disease (AD) pathologies. This study shows microglial cytokine release affects amyloid-β protein precursor (AβPP), tau, apolipoprotein E (ApoE), and lipid metabolism in neuronal cells.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the immune cells of the brain, play a critical role in neuroinflammation.
- Genetic studies link microglial gene expression to Alzheimer's disease (AD) risk.
- Microglial cytokine release is a key functional component implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the impact of microglial cytokine release on AD-related cellular changes.
- To determine how activated microglia-conditioned medium affects neuronal cells concerning AD biomarkers.
- To assess the influence of microglial factors on amyloid-β protein precursor (AβPP), tau, apolipoprotein E (ApoE), and lipid metabolism.
Main Methods:
- Activation of mouse BV2 microglial cells using lipopolysaccharide (LPS).
- Collection of conditioned medium from activated microglia.
- Exposure of human neuronal SH-SY5Y cells to conditioned medium.
- Assessment of AβPP, tau, ApoE, and lipid profiles in neuronal cells.
Main Results:
- AβPP levels were unchanged, with a slight decrease in soluble AβPPα, suggesting altered processing.
- Tau mRNA increased, but total and phosphorylated tau remained stable.
- ApoE mRNA increased, yet ApoE protein levels decreased.
- Neuronal cells showed reduced lipid droplets and increased lipid oxidation.
Conclusions:
- Cytokine release from activated microglia influences neuronal AβPP processing, tau expression, ApoE levels, and lipid metabolism.
- These findings highlight the role of microglial function in modulating AD-relevant cellular pathologies.
- Microglial-derived factors represent potential therapeutic targets for Alzheimer's disease.
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