DESCRIPTION:

Chronic ethanol - Ethanol vs. Control DNA microarray Change in gene expression Pre-equilibrated with ethanol vapor, flies were exposed in an inebriometer from which they were eluted at one minute intervals. The mean elution time is a measure of alcohol sensitivity. To measure alcohol tolerance, we subjected flies to an initial exposure to ethanol, and recorded their elution profile as described above. We allowed the flies to recover for 2 h, and then repeated the assay with the same flies. The difference in the shift of modal elution times between the second and first assa The quantitative estimate of expression of each probe set is the Signal (Sig) metric, as described in the Affymetrix Microarray Suite, Version 5.0. We performed analysis of variance to identify probe sets with significant differences in expression between the three treatments, and a false positive discovery rate of q < 0.05 to account for multiple tests. Significant probe sets were further analyzed by post hoc Tukey tests to identify which samples accounted for transcriptional differences betwee Probe sets with altered transcriptional regulation after ethanol exposure with q < 0.001. These transcripts show altered expression only after the second exposure to alcohol. (NIF Table ID 382 [221.5])

LABEL:

Chronic ethanol - Ethanol vs. Control

SCORE TYPE:

P-Value

THRESHOLD:

<= 8.83E-04

GENES IN THRESHOLD:

15

DATE ADDED:

2010-11-03

DATE UPDATED:

2024-10-22

SPECIES:

URI:

http://neuinfo.org/

AUTHORS:

Morozova TV, Anholt RR, Mackay TF

TITLE:

Transcriptional response to alcohol exposure in Drosophila melanogaster.

JOURNAL:

Genome biology None 2006, Vol 7, pp. R95

ABSTRACT:

BACKGROUND: Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. RESULTS: We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of genes affecting olfaction, rapid upregulation of biotransformation enzymes and, concomitant with development of tolerance, altered transcription of transcriptional regulators, proteases and metabolic enzymes, including biotransformation enzymes and enzymes associated with fatty acid biosynthesis. Functional tests of P-element disrupted alleles corresponding to genes with altered transcription implicated 75% of these in the response to alcohol, two-thirds of which have human orthologues. CONCLUSION: Expression microarray analysis is an efficient method for identifying candidate genes affecting complex behavioral and physiological traits, including alcohol abuse. Drosophila provides a valuable genetic model for comparative genomic analysis, which can inform subsequent studies in human populations. Transcriptional analyses following alcohol exposure in Drosophila implicate biotransformation pathways, transcriptional regulators, proteolysis and enzymes that act as metabolic switches in the regulation of fatty acid metabolism as important targets for future studies of the physiological consequences of human alcohol abuse. PUBMED: 17054780
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