Can bacterial products reach the brain after alcohol binge drinking?

Abstract

Introduction: Alcohol binge drinking (ABD) induces leaky gut, allowing the entry of lipopolysaccharide (LPS), a bacterial component, to the systemic circulation, activating the innate immune system and inducing neuroinflammation, leading to cognitive and emotional changes. It is unknown whether LPS could reach the brain to exert its functions, although recent evidence suggests that small parts of this LPS, such as Lipid A, could be transported through apolipoproteins in physiological conditions. Here, we studied the presence of Lipid A in its free form or bound to specific apolipoproteins (ApoAI and ApoB) or its receptor TLR4 in prefrontal cortex (PFC) of male and female rats exposed to an ABD model by gavage. Methods: Rats were exposed to intragastric binge ethanol administrations (3 g/kg ethanol (30% w/v), 3 times/day) for 4 days. Free Lipid A, ApoAI, ApoB and TLR4 levels and binding aggregates were measured in the prefrontal cortex (PFC) by western blot and Co-Immunoprecipitation. Results: Lipid A, ApoAI and ApoB were not increased in their free forms in ABD rats compared with controls. However, Lipid A / ApoAI and Lipid A / ApoB ratios were increased after ABD, indicative of the binding of Lipid A with these apolipoproteins, as confirmed by Co-Immunoprecipitation. Additionally, the LPS agonist TLR4, which is a known core element of neuroinflammation, was found increased in its free form in ABD animals. Conclusion: The presence of bacterial products joined to apolipoproteins in the rat PFC suggests that LPS may infiltrate the brain in ABD conditions and could be related to the neuroinflammatory LPS/TLR4 signaling. No sexual differences were found. Current studies are exploring the impact of this Apo-Lipid A binding in ABD-induced emotional/cognitive alterations.