Repetitive binge-like consumption based on the Drinking-in-the-Dark model alters the microglial population in the mouse hippocampus

J Integr Neurosci. 2021 Dec 30;20(4):933-943. doi: 10.31083/j.jin2004094.

Abstract

Alcoholism causes various maladaptations in the central nervous system, including the neuroimmune system. Studies of alcohol-induced dysregulation of the neuroimmune system generally focus on alcohol dependence and brain damage, but our previous research indicates that repetitive binge-like consumption perturbs cytokines independent of cell death. This paper extends that research by examining the impact of binge-like consumption on microglia in the hippocampus and the amygdala. Microglia were assessed using immunohistochemistry following binge-like ethanol consumption based on Drinking-in-the-Dark model. Immunohistochemistry results showed that binge-like ethanol consumption caused an increase in Iba-1 immunoreactivity and the number of Iba-1+ cells after one Drinking-in-the-Dark cycle. However, after three Drinking-in-the-Dark cycles, the number of microglia decreased in the hippocampus. We showed that in the dentate gyrus, the average immunoreactivity/cell was increased following ethanol exposure despite the decrease in number after three cycles. Likewise, Ox-42, an indicator of microglia activation, was upregulated after ethanol consumption. No significant effects on microglia number or immunoreactivity (Iba-1 nor Ox-42) were observed in the amygdala. Finally, ethanol caused an increase in the expression of the microglial gene Aif-1 during intoxication and ten days into abstinence, suggesting persistence of ethanol-induced upregulation of microglial genes. Altogether, these findings indicate that repetitive binge-like ethanol is sufficient to elicit changes in microglial reactivity. This altered neuroimmune state may contribute to the development of alcohol use disorders.

Keywords: Alcohol use disorder; Amygdala; Binge-like drinking; Hippocampus; Microglia; Neuroimmune.

MeSH terms

  • Alcoholism* / immunology
  • Alcoholism* / metabolism
  • Amygdala / drug effects
  • Amygdala / immunology
  • Amygdala / metabolism
  • Animals
  • Behavior, Animal / physiology
  • Binge Drinking* / immunology
  • Binge Drinking* / metabolism
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology*
  • Disease Models, Animal
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Hippocampus* / drug effects
  • Hippocampus* / immunology
  • Hippocampus* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia* / drug effects
  • Microglia* / immunology
  • Microglia* / metabolism

Substances

  • Central Nervous System Depressants
  • Ethanol