Withdrawal from chronic alcohol exposure leads to tissue-specific recovery of the zebrafish transcriptome

Alcohol consumption can lead to a wide-range of systemic disorders brought about by transcriptional changes. Recent studies have shown altered behavioral and expression changes in zebrafish on exposure to alcohol. We have identified changes associated with transcriptome profiles in response to chronic alcohol exposure and extent of recovery upon withdrawal. Our results indicate a tissue-specific response where the brain responds positively to withdrawal when compared to liver. We identified two distinct classes of genes in response to withdrawal from alcohol exposure – one group recovered the pre-exposure expression profile while the other set of genes retained altered expression profiles despite withdrawing from alcohol whose altered expression profiles remained changed even after withdrawal. We also examined gender-specific responses to alcohol. Male fish appear to be more susceptible to changes induced by alcohol indicated by a higher percent of genes appearing to change their expression profiles when compared to females. Female fish appear to show a better recovery as compared to males as a sizable number of genes appear to have their expression levels recovered upon the introduction of withdrawal. Overall, our work identifies pathways / genes perturbed by exposure to alcohol and demonstrates the extent of tissue-specific transcriptional changes and takes into account the variability of gender in assessing the effect of chronic alcoholism and withdrawal. Overall design: Methods: Brain and liver tissue from six groups of zebrafish (Danio rerio, shortfin,'AB' strain) of both sexes i.e, Male control, Female control, Male alcohol-exposed, Female alcohol exposed, Male withdrawal and Female withdrawal were pooled in respective groups and their mRNA profiles were generated using Illumina HiSeq 2000. There were 14 samples from brain tissue i.e two replicates of male control, three replicates of female control, two replicates of Male alcohol-exposed, two replicates of Female alcohol exposed, three replicates of Male withdrawal and two replicates of Female withdrawal group. There were 12 samples of liver tissues i.e two replicates for each of the six groups. The sequence reads were quality checked using FastQC, mapped to reference genome (danRer10) using STAR, abundance estimates of transcripts calculated using RSEM and differential expression was performed using EBSeq.