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Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro

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Abstract

Alpha (α)-synuclein neuronal effects are continually being defined although its role in regulating glial phenotypes remains unclear. An ability to regulate microglial activation was investigated using primary cultures from wild type and α-synuclein deficient mice (Snca /). Snca / microglia demonstrated increased secretion of the cytokine tumor necrosis factor-alpha (TNF-α), impaired phagocytic ability, elevated prostaglandin levels, and increased protein levels of key enzymes in lipid-mediated signaling events, cytosolic phospholipase (cPLA2), cyclooxygenase-2 (Cox-2) and phospholipase D2 (PLD2) when compared to wild type cells. Increased cytokine secretion and cPLA2 and Cox-2 levels in Snca / microglia were partially attenuated by inhibiting PLD-dependent signaling with n-butanol treatment.

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Acknowledgments

This work was supported by the National Institutes of Health [2P20RR017600, 1R01AG026330, 1R21NS060141]; and the North Dakota National Science Foundation Experimental Program to Stimulate Competitive Research (EPSCoR) [RRNI EPS-0447679]. We are grateful to Ms. Kendra Puig for help with the statistical analysis.

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Correspondence to Colin K. Combs.

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Austin, S.A., Rojanathammanee, L., Golovko, M.Y. et al. Lack of Alpha-Synuclein Modulates Microglial Phenotype In Vitro. Neurochem Res 36, 994–1004 (2011). https://doi.org/10.1007/s11064-011-0439-9

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