Differential expression of microRNAs in the hippocampi of male and female rodents after chronic alcohol administration

Background Women are more vulnerable than men to the neurotoxicity and severe brain damage caused by chronic heavy alcohol use. In addition, brain damage due to chronic heavy alcohol use may be associated with sex-dependent epigenetic modifications. This study aimed to identify microRNAs (miRNAs) and their target genes that are differentially expressed in the hippocampi of male and female animal models in response to alcohol. Methods After chronic alcohol administration (3~3.5 g/kg/day) in male (control, n = 10; alcohol, n = 12) or female (control, n = 10; alcohol, n = 12) Sprague-Dawley rats for 6 weeks, we measured body weights and doublecortin (DCX; a neurogenesis marker) concentrations and analyzed up- or downregulated miRNAs using GeneChip miRNA 4.0 arrays. The differentially expressed miRNAs and their putative target genes were validated by RT-qPCR. Results Alcohol attenuated body weight gain only in the male group. On the other hand, alcohol led to increased serum AST in female rats and decreased serum total cholesterol concentrations in male rats. The expression of DCX was significantly reduced in the hippocampi of male alcohol-treated rats. Nine miRNAs were significantly up- or downregulated in male alcohol-treated rats, including upregulation of miR-125a-3p, let-7a-5p, and miR-3541, and downregulation of their target genes (Prdm5, Suv39h1, Ptprz1, Mapk9, Ing4, Wt1, Nkx3-1, Dab2ip, Rnf152, Ripk1, Lin28a, Apbb3, Nras, and Acvr1c). On the other hand, 7 miRNAs were significantly up- or downregulated in alcohol-treated female rats, including downregulation of miR-881-3p and miR-504 and upregulation of their target genes (Naa50, Clock, Cbfb, Arih1, Ube2g1, and Gng7). Conclusions These results suggest that chronic heavy alcohol use produces sex-dependent effects on neurogenesis and miRNA expression in the hippocampus and that sex differences should be considered when developing miRNA biomarkers to diagnose or treat alcoholics.

OMEGA-3 Interventions in Alcohol Dependence and Related Outcomes: A Systematic Review and Propositions

Background: Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited, presenting several side effects and a modestly higher efficacy compared to placebo. The administration of omega-3 might bring new perspectives to relapse prevention. Methods: This systematic review aimed to analyze the available literature, compiling the studies that used omega-3 to prevent relapse in alcohol dependents. Results: The databases used were PubMed and Web of Science. We identified 2,231 studies and only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results. Conclusion: Despite the reduced number of studies, omega-3 interventions seem to be promising for controlling issues related to alcohol dependence.