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Alcohol drinking during early adolescence activates microglial cells and increases frontolimbic Interleukin-1 beta and Toll-like receptor 4 gene expression, with heightened sensitivity in male rats compared to females.
- Source :
-
Neuropharmacology [Neuropharmacology] 2021 Oct 01; Vol. 197, pp. 108698. Date of Electronic Publication: 2021 Jul 09. - Publication Year :
- 2021
-
Abstract
- Adolescent drinking is risky because neural circuits in the frontal lobes are undergoing maturational processes important for cognitive function and behavioral control in adulthood. Previous studies have shown that myelinated axons in the medial prefrontal cortex (mPFC) are particularly sensitive to alcohol drinking, especially in males. Pro-inflammatory mediators like toll-like receptor 4 (TLR4) and interleukin-1 beta (IL1b) have been implicated in alcohol induced-inflammation and demyelination; thus, herein we test the hypothesis that voluntary alcohol drinking early in adolescence elicits a pro-inflammatory state that is more pronounced in the brain of males compared to females. Adolescent male and female Wistar rats self-administered sweetened alcohol or sweetened water from postnatal days 28-42 and separate sets of brains were processed for 1) immunolabeling for ionized calcium-binding adapter molecule 1 to analyze microglial cell morphology, or 2) qPCR analysis of gene expression of pro-inflammatory mediators. Binge drinking alcohol activated microglia in the mPFC and hippocampus of both males and females, suggesting that voluntary alcohol exposure initiates an inflammatory response. Il1b mRNA was upregulated in the mPFC of both sexes. Conversely, Tlr4 mRNA levels were elevated after drinking only in males, which could explain more robust effects of alcohol on myelin in this region in developing males compared to females. Il1b mRNA changes were not observed in the hippocampus, but alcohol elevated Tlr4 mRNA in both sexes, highlighting regional specificity in inflammatory responses to alcohol. Overall, these findings give insight into potential mechanisms by which low-to-moderate voluntary alcohol intake impacts the developing brain. This article is part of the special Issue on 'Vulnerabilities to Substance Abuse'.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Alcohol Drinking psychology
Animals
Binge Drinking genetics
Binge Drinking psychology
Conditioning, Operant
Female
Gene Expression Regulation
Hippocampus drug effects
Hippocampus metabolism
Interleukin-1beta drug effects
Limbic System drug effects
Male
RNA, Messenger biosynthesis
RNA, Messenger genetics
Rats
Rats, Wistar
Self Administration
Sex Characteristics
Toll-Like Receptor 4 drug effects
Alcohol Drinking genetics
Alcohol Drinking pathology
Interleukin-1beta genetics
Limbic System metabolism
Toll-Like Receptor 4 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 197
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34252404
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2021.108698