Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis

BACKGROUND: Microglial activation contributes to the neuropathology associated with chronic alcohol exposure and withdrawal, including the expression of inflammatory and anti-inflammatory genes. In the current study, we examined the transcriptome of primary rat microglial cells following incubation with alcohol alone, or alcohol together with a robust inflammatory stimulus.

METHODS: Primary microglia were prepared from mixed rat glial cultures. Cells were incubated with 75 mM ethanol alone or with proinflammatory cytokines ("TII": IL1beta, IFNgamma, and TNFalpha). Isolated mRNA was used for RNAseq analysis and qPCR. Effects of alcohol on phagocytosis were determined by uptake of oligomeric amyloid beta.

RESULTS: Alcohol induced nitrite production in control cells and increased nitrite production in cells co-treated with TII. RNAseq analysis of microglia exposed for 24 h to alcohol identified 312 differentially expressed mRNAs ("Alc-DEs"), with changes confirmed by qPCR analysis. Gene ontology analysis identified phagosome as one of the highest-ranking KEGG pathways including transcripts regulating phagocytosis. Alcohol also increased several complement-related mRNAs that have roles in phagocytosis, including C1qa, b, and c; C3; and C3aR1. RNAseq analysis identified over 3000 differentially expressed mRNAs in microglia following overnight incubation with TII; and comparison to the group of Alc-DEs revealed 87 mRNAs modulated by alcohol but not by TII, including C1qa, b, and c. Consistent with observed changes in phagocytosis-related mRNAs, the uptake of amyloid beta1-42, by primary microglia, was reduced by alcohol.

CONCLUSIONS: Our results define alterations that occur to microglial gene expression following alcohol exposure and suggest that alcohol effects on phagocytosis could contribute to the development of Alzheimer's disease.

Additional Info

  • Authors:

    Kalinin,S.; Gonzalez-Prieto,M.; Scheiblich,H.; Lisi,L.; Kusumo,H.; Heneka,M.T.; Madrigal,J.L.M.; Pandey,S.C.; Feinstein,D.L.

  • Issue: J Neuroinflammation. / pages 141- / volume 15
  • Published Date: 2018/5/14
  • More Information:

    For more information about this abstract, please contact
    This email address is being protected from spambots. You need JavaScript enabled to view it. at the Deutsche Weinakademie GmbH

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