Abstract
Chronic alcohol abuse leads to severe brain damage. Although the underlying neuropathological processes are largely unknown, recent studies show that chronic alcohol consumption leads to neuroinflammation and may result in neurodegeneration and impaired neuronal connectivity. Long-term alcohol consumption promotes the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, and activates microglia cells in the brain. As it has not yet been investigated to what extent these processes dependent on the duration of alcohol consumption or whether microglia are source of pro-inflammatory cytokines in vivo, this study investigated the expression of the pro-inflammatory cytokine, IL-1β, in microglia at different time points in mice chronically exposed to alcohol. In the present study, we exposed mice to 2, 6, and 12 months of alcohol consumption, and using immunohistochemistry, analyzed the expression of the microglial marker, Iba1, together with the pro-inflammatory cytokine IL-1β in several cortical regions. Moreover, we investigated the effect of pro-inflammatory activation of microglia on neuronal density. We found that alcohol drinking progressively enhanced IL-1β expression in microglia, which was paralleled with an overall increased microglial density after long-term alcohol consumption. However, we did not find changes in the neuronal density or cortical volume after long-term alcohol consumption. These data show that 12 months of alcohol drinking leads to a pro-inflammatory activation of microglia, which may contribute to impaired neuronal connectivity in the cortex. Anti-inflammatory drug treatment during or after chronic alcohol consumption may thus provide a strategy for restoring brain homeostasis.
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Acknowledgements
We thank Greta Krusch for helping with the immunostainings and Abigail Polter for the comments on the manuscript.
Funding
This work was supported by grants from the Bundesministerium für Forschung und Bildung (NGFN2, FKZ 01GS08156).
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IR and BP were responsible for the study concept, data analysis, and draft of the manuscript. BP, EE, and AM contributed to the acquisition of animal data.
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Pradier, B., Erxlebe, E., Markert, A. et al. Microglial IL-1β progressively increases with duration of alcohol consumption. Naunyn-Schmiedeberg's Arch Pharmacol 391, 455–461 (2018). https://doi.org/10.1007/s00210-018-1475-7
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DOI: https://doi.org/10.1007/s00210-018-1475-7