Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior

dc.creatorSkinner, Michael K.en
dc.creatorAnway, Matthew D.en
dc.creatorSavenkova, Marina I.en
dc.creatorGore, Andrea C.en
dc.creatorCrews, Daviden
dc.date.accessioned2013-03-14T13:38:17Zen
dc.date.available2013-03-14T13:38:17Zen
dc.date.issued2008-11-18en
dc.description.abstractEmbryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.en
dc.description.departmentBiological Sciences, School ofen
dc.description.sponsorshipThis research was supported by a grant from the National Institute of Environmental Health Sciences, NIEHS to MKS.en
dc.identifier.citationSkinner MK, Anway MD, Savenkova MI, Gore AC, Crews D (2008) Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior. PLoS ONE 3(11): e3745. doi:10.1371/journal.pone.0003745en
dc.identifier.urihttp://hdl.handle.net/2152/19734en
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.rightsAttribution 3.0 United Statesen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en
dc.subjectAmygdalaen
dc.subjectAnimal behavioren
dc.subjectCalcium signalingen
dc.subjectGene expressionen
dc.subjectHippocampusen
dc.subjectMicroarraysen
dc.subjectRatsen
dc.subjectTranscriptome analysisen
dc.titleTransgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavioren
dc.typeArticleen

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