title: Ethanol modifies the effect of handling stress on gene expression: problems in the analysis of two-way gene expression studies in mouse brain.
abstract: Studies analysing the effects of acute treatments on animal behaviour and brain biochemistry frequently use pairwise comparisons between sham-treated and -untreated animals. In this study, we analyse expression of tPA, Grik2, Smarca2 and the transcription factor, Sp1, in mouse cerebellum following acute ethanol treatment. Expression is compared to saline-injected and -untreated control animals. We demonstrate that acute i.p. injection of saline may alter gene expression in a gene-specific manner and that ethanol may modify the effects of sham treatment on gene expression, as well as inducing specific effects independent of any handling related stress. In addition to demonstrating the complexity of gene expression in response to physical and environmental stress, this work raises questions on the interpretation and validity of studies relying on pairwise comparisons.
authors.affiliation: Trafford Centre for Medical Research, University of Sussex, Falmer, Brighton, UK.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Rulten
authors.forename: Tamzin L
authors.initials: TL
authors.lastname: Ripley
authors.forename: Ektor
authors.initials: E
authors.lastname: Manerakis
authors.forename: David N
authors.initials: DN
authors.lastname: Stephens
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Mayne
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics*; D002531:Cerebellum / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006234:Handling, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097806:GluK2 Kainate Receptor
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D012333:RNA, Messenger; D018092:Kainic Acid Receptors; D016329:Sp1 Transcription Factor; D010959:Tissue Plasminogen Activator; D014157:Transcription Factors; D000097806:GluK2 Kainate Receptor; C499503:Smarca2 protein, mouse