Expression of Toll-like receptors in emotiogenic structures of rat brain is changed under longterm alcohol consumption and ethanol withdrawal

Abstract

Recent studies have provided strong evidence that long-term ethanol consumption leads to activation the mechanisms of neuroimmune signaling. Recently, much attention has been focused on the study of toll-like receptors (Toll-like receptors, TLRs), which play one of the key roles in the mechanisms of activation of the innate immune system in brain structures subsequently ethanol consumption. It is known that the activation of TLRs leads to the release of many proinflammatory cytokines with the resulting neuroinflammatory process. There are suggestions that TLRs may also be involved in the modulation of neurotransmitter systems of the brain, thereby contributing to the formation of pathological dependence on ethanol. The goal of our work was to study the level of expression the genes of TLRs (TLR3, TLR4, TLR7) and pro-inflammatory cytokine genes (IL-1β, CCL2) in the rat brain (amygdala, hippocampus, medial entorhinal cortex, striatum) under conditions of prolonged alcoholization and on different periods of alcohol withdrawal, which was previously not studied by researchers. Prolonged alcoholization of rats with ethanol did not lead to changes in levels mRNA of TLRs in the studied structures of the rat brain, with the exception of a small increase in the level of TLR3 mRNA in the hippocampus of prolonged alcoholized rats and a slight increase in the level of TLR3 mRNA in mEC. However, gene expression of TLRs undergoes changes in all the structures of the rat brain studied by us at different periods of alcohol withdrawal. The increased level of expression of both TLRs and proinflammatory genes in the period of alcohol withdrawal in the rat brain hippocampus deserves special attention, which indicates the presence of a persistent neuroinflammatory process in this brain structure in the period of alcohol withdrawal, which is probably supported with the participation of TLR-dependent signaling. The study of the mechanisms of inflammatory process activation by TLR-dependent signaling in different brain structures can open new targets for drug exposure. Such drugs can be used in the treatment of alcoholism.