Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Fast and chronic ethanol tolerance - time course

ABSTRACT: To better understand the molecular mechanisms underlying ethanol action we have developed an assay system to study sensitivity and fast and chronic tolerance to the sedative effects of ethanol. Flies developed fast ethanol tolerance after single exposure to 50% of ethanol vapor for 40 min. Flies can also develope chronic ethanol tolerance after 5x 40 min exposure to 50% ethanol vapor interspersed with 4x 80 min exposure to 10% ethanol vapor. We used microarray analysis to identify genes involved in the development of fast and chronic ethanol tolerance in Drosophila. More than 600 hundred genes were found to have changed their expression level in response to different ethanol treatment. Among these genes, Homer was picked for further study and is demonstrated that its expression in ellipsoid body is critical for the normal sensitivity and fast toleance to ethanol. Keywords: time course Whole heads of 3 groups of Drosophila were separated for RNA extraction and hybridization on Affymetrix microarrays. These 3 groups of flies were treated with different ethanol treatment. Naive group of flies (GSM101531, GSM101532, GSM101533, GSM101534, GSM101535, GSM101536) received only 50 min of humidified air. Fast group of flies (GSM101537, GSM101538, GSM101539, GSM101540, GSM101541, GSM101542) received humidified air for 50 min followed by a single exposure of 50% ethanol vapor for 40 min. Chronic group of flies (GSM101543, GSM101544, GSM101545, GSM101546, GSM101547, GSM101548) ) received humidified air for 50 min followed by 5 exposures of 50% ethanol vapor for 40 min.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Zhiyong Yang

PROVIDER: E-GEOD-4531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Drosophila homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance.

Urizar Nancy L NL Yang Zhiyong Z Edenberg Howard J HJ Davis Ronald L RL

The Journal of neuroscience : the official journal of the Society for Neuroscience 20070401 17

The molecular mechanisms occurring in the nervous system that underlie behavioral responses to ethanol remain poorly understood. Here, we report that molecular requirements for two of these responses, initial sensitivity and the development of rapid tolerance, comap to the same small set of neurons. We show that null homer mutant flies exhibit both increased sensitivity to the sedative effects of ethanol and failure to develop normal levels of rapid tolerance. Both the sensitivity and rapid tole ...[more]

PMID: 17460067

Similar Datasets

Project description:Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. We performed artificial selection for alcohol sensitivity for 25 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. Experiment Overall Design: Starting with flies from Raleigh natural population (see material and methods) we performed artificial selection for alcohol sensitivity for 35 generation. In each generations we scored 60 males and females, separately, from each line (resistant, sensitive, and control)using inebriometer, and the 20 highest-scoring flies from the resistant lines and the 20 lowest-scoring flies from the sensitive lines were selected as parents for the next generation. Control line flies were scored each generation and 20 random flies were used as parents. Experiment Overall Design: At generation 25, two replicates of 15 three-five day old virgin males and females were collected from each selection line. Total RNA was extracted from the 24 samples . Biotinylated cRNA probes were hybridized to high density oligonucleotide microarrays (Affymetrix, Inc. Drosophila GeneChip 2.0) and visualized with a streptavidin-phycoerythrin conjugate, as described in the Affymetrix GeneChip Expression Analysis Technical Manual (2000), using internal references for quantification. The quantitative estimate of expression of each probe set is the Signal (Sig) metric, as described in the Affymetrix Microarray Suite, Version 5.0.

Dataset Information

Fast and chronic ethanol tolerance - time course

Publications

Drosophila homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure