Study of Neuroinflammation in the Rat Hippocampus during Ethanol Exposure and Pharmacological Correction with Azithromycin: New Data and Future Perspectives.

Abstract

With prolonged ethanol ingestion, disturbances in the emotional spectrum develop, and memory problems are noted. These symptoms could be mediated by the development of neurochemical changes in the hippocampus of the brain. Although there is evidence that hippocampus is vulnerable to chronic alcohol intoxication and that neuroinflammation and neurodegeneration develop in this brain region, the key molecular mechanisms have not been identified. The aim of the study was to investigate changes in the immune system in the periphery as well as in the hippocampus of rat brain during ethanol exposure and during pharmacological correction with azithromycin (AZM). Long-term ethanol exposure was modeled by injecting rats with a 20% ethanol solution (4 g/kg) for 4 weeks. General biochemical and clinical blood analysis was performed in animals. Expression levels of the cytokine genes (Il1β, Ccl2, Il6, Il11, Il13, Tnfα, Tgfβ), Toll-like receptor system genes (Tlr3, Tl4, Tlr7, Nfkb1, Hmgb1), and TLR system-related microRNA molecules (miR-182, miR-155-5p, miR-96-5p, miR-let-7b) were evaluated in the hippocampus. IL-1β protein content was also assessed in the hippocampus. Prolonged exposure to alcohol caused increase in the mRNA and protein levels of IL-1β, and decrease in the mRNA levels of Tnfα, Il11, Tlr3, and Tlr7. The contents of miRlet7b, miR96, and miR155 were downregulated in the hippocampus after long-term alcohol exposure. Elevated levels of THE Il1β mRNA and protein and Hmgb1 mRNA were maintained under conditions of ethanol abstinence. The Tlr3 mRNA levels were decreased after abstinence. Administration of AZM reduced the IL1β, TLR3, and HMGB1 mRNA levels under conditions of ethanol abstinence; and at higher doses of the drug decrease in the IL-1β protein levels in the hippocampus of rat brain was observed. Thus, the study provided new insights into the mechanisms of neuroinflammation in the hippocampus during prolonged exposure to ethanol and upon abstinence. The obtained results allowed us to suggest a number of tasks for further studies in this direction.