TLR3 Induction During Long-Term Alcoholization Increases the Content of Rat Brain Interferons by TRAIL Signaling

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Biomedical chemistry, 2021-10, Vol.15 (4), p.306-312
• Main Authors: Airapetov, M. I., Eresko, S. O., Vasiliev, A. K., Vasilieva, V. Y., Bychkov, E. R., Lebedev, A. A., Shabanov, P. D.
• Format: Article
• Language: English
• Subjects: Agonists; Alcoholism; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Drug abuse; Ethanol; Immune system; Innate immunity; Intracellular signalling; Medicinal Chemistry; mRNA; Poly (I:C); Prefrontal cortex; TLR3 protein; Toll-like receptors; β-Interferon; γ-Interferon
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S1990750821040028

The pathogenetic mechanisms associated with alcohol use include dysregulation of the innate immune system mechanisms in the brain. Increased TLR3 expression was found in the postmortem material of the prefrontal cortex of humans. An increase in the TLR3 signaling activity leads to the induction of interferons (IFNs). IFNs are associated with depressive symptoms and, therefore, may play a role in the pathogenesis of alcoholism; however, the exact mechanisms of the ethanol effects on intracellular signaling pathways are not fully elucidated and their study was the purpose of this work. The experimental results showed that ethanol and the TLR3 agonist Poly (I:C) increased the content of TLR3, IFNβ, and IFNγ mRNA in the prefrontal cortex. In addition, expression of the TRAIL encoding gene also increased, and this increase positively correlated with the mRNA content of TLR3, IFNβ and IFNγ both under alcoholization conditions and after injections of the TLR3 agonist. The data obtained may indicate that alcoholization is able to activate TLR3-TRAIL-IFN-signaling in the medial prefrontal cortex (mPFC) of the rat brain.