Microglial IL-1β progressively increases with duration of alcohol consumption
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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.
KeywordsNeuroinflammation Pro-inflammatory cytokine Iba1 Chronic alcohol
We thank Greta Krusch for helping with the immunostainings and Abigail Polter for the comments on the manuscript.
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Alfonso-Loeches S, Urena-Peralta J, Morillo-Bargues MJ, Gomez-Pinedo U, Guerri C (2016) Ethanol-induced TLR4/NLRP3 neuroinflammatory response in microglial cells promotes leukocyte infiltration across the BBB. Neurochem Res 41(1-2):193–209. https://doi.org/10.1007/s11064-015-1760-5 CrossRefPubMedGoogle Scholar
- Alfonso-Loeches S, Urena-Peralta JR, Morillo-Bargues MJ, Oliver-De La Cruz J, Guerri C (2014) Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. Front Cell Neurosci 8:216. https://doi.org/10.3389/fncel.2014.00216 CrossRefPubMedPubMedCentralGoogle Scholar
- Chastain LG, Sarkar DK (2014) Role of microglia in regulation of ethanol neurotoxic action. Int Rev Neurobiol 118:81–103. https://doi.org/10.1016/B978-0-12-801284-0.00004-X CrossRefPubMedGoogle Scholar
- Cui C, Noronha A, Warren KR, Koob GF, Sinha R, Thakkar M, Matochik J, Crews FT, Chandler LJ, Pfefferbaum A, Becker HC, Lovinger D, Everitt BJ, Egli M, Mandyam CD, Fein G, Potenza MN, Harris RA, Grant KA, Roberto M, Meyerhoff DJ, Sullivan EV (2015) Brain pathways to recovery from alcohol dependence. Alcohol 49(5):435–452. https://doi.org/10.1016/j.alcohol.2015.04.006 CrossRefPubMedPubMedCentralGoogle Scholar
- Grathwohl SA, Kälin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S, Aguzzi A, Staufenbiel M, Mathews PM, Wolburg H, Heppner FL, Jucker M (2009) Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12(11):1361–1363. https://doi.org/10.1038/nn.2432 CrossRefPubMedPubMedCentralGoogle Scholar
- Marshall SA, McClain JA, Kelso ML, Hopkins DM, Pauly JR, Nixon K (2013) Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: the importance of microglia phenotype. Neurobiol Dis 54:239–251. https://doi.org/10.1016/j.nbd.2012.12.016 CrossRefPubMedPubMedCentralGoogle Scholar
- Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 4th edn. Academic Press, San DiegoGoogle Scholar
- Piyanova A, Albayram O, Rossi CA, Farwanah H, Michel K, Nicotera P, Sandhoff K, Bilkei-Gorzo A (2013) Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated lipofuscin accumulation in the hippocampus. Mech Ageing Dev 134(9):391–399. https://doi.org/10.1016/j.mad.2013.08.001 CrossRefPubMedGoogle Scholar
- Pradier B, Jeub M, Markert A, Mauer D, Tolksdorf K, van de Putte T, Seuntjens E, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Huylebroeck D, Beck H, Zimmer A, Rácz I (2014) Smad-interacting protein 1 affects acute and tonic, but not chronic pain. Eur J Pain 18(2):249–257. https://doi.org/10.1002/j.1532-2149.2013.00366.x CrossRefPubMedGoogle Scholar
- Vetreno RP, Yaxley R, Paniagua B, Crews FT (2016a) Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction. Addict Biol 21(4):939–953. https://doi.org/10.1111/adb.12232 CrossRefPubMedGoogle Scholar