ApoAI-LPS aggregates are found in the frontal cortex of female rats after alcohol binge drinking: effects of ApoAI mimetic peptide on behaviour

Abstract

Alcohol binge drinking (ABD) induces a disruption of the intestinal barrier, allowing the entry of bacterial lipopolysaccharide (LPS) to the bloodstream. Some apolipoproteins (Apo), such as ApoAI, transport the LPS to the liver to be eliminated but little is known about a possible transport to the brain and its consequences. Here, we explored the expression of ApoAI in blood and brain after ABD and its binding to LPS components (Lipid A) in frontal cortex (FC), an area where alcohol induces neuroinflammation. We also examined the consequences of an ApoAI mimetic peptide (4F) administration in behaviours related to ABD-induced neuroinflammation. Female Wistar rats (200-225g) received intermittent doses of ethanol (3 g/Kg, i.g., 30% ethanol, 4 days/3 times/day) in a 2-day/2-day off protocol. 4F peptide (APL180, 5 mg/Kg, i.p.) was injected 15 min before alcohol gavages. Plasma ApoAI and LPS levels were measured by commercial kits; ApoAI and Lipid A levels in FC and the aggregate Lipid A/ApoAI were measured by western blotting (and co-immunoprecipitation). Rats were evaluated with the Elevated Plus Maze (EPM), Forced Swimming test (FST) and Novel Object Recognition (NOR) test. Plasma ApoAI was elevated in ABD rats whereas increases in LPS did not reach statistical significance. In FC, ApoAI and Lipid A were detected, with no difference between groups. Interestingly, increases in the Lipid A/ApoAI ratio were observed in ethanol group vs control, indicative of the binding of Lipid A to ApoAI. ABD rats showed a reduced anxiety- like behaviour but depressive-like behaviour during early abstinence and less latency to explore the novel object versus controls, with higher discrimination indexes. 4F administration showed no behavioural changes. Our results suggest that LPS infiltrates the brain in ABD conditions as an aggregate with ApoAI. The exogenous administration of an ApoAI mimetic peptide had no effect on ABD-induced alterations during abstinence.