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Prolonged alcohol consumption influences microRNA expression in the nucleus accumbens of the rat brain
M I Airapetov1, S O Eresko2, S A Shamaeva3
1Institute of Experimental Medicine, St. Petersburg, Russia; Military Medical Academy of S.M. Kirov, St. Petersburg, Russia.
Abstract:
The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression levels of miR-let7b, miR-96, miR-182, miR-155, and the mRNA content of HMGB1, TLR3, TLR4 in the nucleus accumbens (NAc) of the brain of rats exposed to long-term alcoholization. The long-term alcoholization caused a decrease in miR-let7b, miR-96, miR-182, and TLR7 mRNA levels; this was accompanied by an increase in miR-155, TLR4, and Hmgb1 mRNA levels in the NAc of rat brain. TLR7 is functionally linked to miR-let7b. The data of a simultaneous decrease in miR-let7b and TLR7 mRNA are of interest for further studies; they may indicate on the lack of functionally significant links between Hmgb1 and the miR-let7b-TLR7 system in NAc. The existing evidence of a functional relationship between TLR4 with miR-155 and miR-182 and our observations on their expression changes during chronic alcoholization are very interesting and require further investigation. The suggestion about the development of neuroinflammatory process in NAc under prolonged alcohol exposure are relevant for studying the level of TLR gene expression in NAc, as well as the expression of miR species, which may have a functional relationship with the TLR system.
Insights
Long-term alcohol exposure alters microRNA (miR) and Toll-like receptor (TLR) levels in the rat brain nucleus accumbens, potentially driving neuroinflammation and neurodegeneration. These changes highlight key molecular pathways involved in alcohol-induced brain damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- MicroRNAs (miRs) and Toll-like receptors (TLRs) play critical roles in neuroinflammation and neurodegeneration.
- Chronic alcohol exposure is a significant risk factor for neurological disorders.
Purpose of the Study:
- To investigate the expression levels of specific miRs (miR-let7b, miR-96, miR-182, miR-155) and mRNAs (HMGB1, TLR3, TLR4, TLR7) in the rat nucleus accumbens (NAc) following long-term alcoholization.
- To explore the potential functional relationships between these molecules in the context of alcohol-induced neuroinflammation.
Main Methods:
- Quantitative analysis of miR and mRNA expression levels in the rat NAc.
- Experimental model of long-term alcohol exposure in rats.
Main Results:
- Long-term alcoholization led to decreased levels of miR-let7b, miR-96, miR-182, and TLR7 mRNA.
- Concurrently, miR-155, TLR4, and HMGB1 mRNA levels increased in the NAc.
- Observed inverse correlation between miR-let7b and TLR7 mRNA suggests a potential lack of functional link with HMGB1 in the NAc.
Conclusions:
- Chronic alcohol exposure significantly alters the expression of miRs and TLRs in the NAc, suggesting a role in neuroinflammation and neurodegeneration.
- The observed changes in miR-155, miR-182, and TLR4 warrant further investigation into their functional relationship during chronic alcoholization.
- These findings provide a basis for understanding the molecular mechanisms underlying alcohol-related neurological damage and suggest potential therapeutic targets.
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