Two-Month Voluntary Ethanol Consumption Promotes Mild Neuroinflammation in the Cerebellum but Not in the Prefrontal Cortex, Hippocampus, or Striatum of Mice
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2024
Author(s)
Sarah Núñez
Justine Castañeda
María Rosa Bono
Type
journal-article
Abstract
<jats:p>Chronic ethanol exposure often triggers neuroinflammation in the brain’s reward system, potentially promoting the drive for ethanol consumption. A main marker of neuroinflammation is the microglia-derived monocyte chemoattractant protein 1 (MCP1) in animal models of alcohol use disorder in which ethanol is forcefully given. However, there are conflicting findings on whether MCP1 is elevated when ethanol is taken voluntarily, which challenges its key role in promoting motivation for ethanol consumption. Here, we studied MCP1 mRNA levels in areas implicated in consumption motivation—specifically, the prefrontal cortex, hippocampus, and striatum—as well as in the cerebellum, a brain area highly sensitive to ethanol, of C57BL/6 mice subjected to intermittent and voluntary ethanol consumption for two months. We found a significant increase in MCP1 mRNA levels in the cerebellum of mice that consumed ethanol compared to controls, whereas no significant changes were observed in the prefrontal cortex, hippocampus, or striatum or in microglia isolated from the hippocampus and striatum. To further characterize cerebellar neuroinflammation, we measured the expression changes in other proinflammatory markers and chemokines, revealing a significant increase in the proinflammatory microRNA miR-155. Notably, other classical proinflammatory markers, such as TNFα, IL6, and IL-1β, remained unaltered, suggesting mild neuroinflammation. These results suggest that the onset of neuroinflammation in motivation-related areas is not required for high voluntary consumption in C57BL/6 mice. In addition, cerebellar susceptibility to neuroinflammation may be a trigger to the cerebellar degeneration that occurs after chronic ethanol consumption in humans.</jats:p>
Cite this document
Berríos-Cárcamo, P., Núñez, S., Castañeda, J., Gallardo, J., Bono, M. R., & Ezquer, F. (2024). Two-month voluntary ethanol consumption promotes mild neuroinflammation in the cerebellum but not in the prefrontal cortex, hippocampus, or striatum of mice. International Journal of Molecular Sciences, 25(8), 4173. https://doi.org/10.3390/ijms25084173
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