1493 Views
0 Replies
Trans generational Epigenetic Programming of the Brain Transcriptome and Anxiety
Behavior
Michael K. Skinner 1, Matthew D. Anway 1, Marina I. Savenkova 1, Andrea C. Gore
2, David Crews 3
1 Center for Reproductive Biology, School of Molecular Biosciences, Washington
State University, Pullman, Washington, United States of America,
2 Division of Pharmacology and Toxicology, University of Texas, Austin, Texas,
United States of America,
3 Section of Integrative Biology, University of Texas, Austin, Texas, United
States of America
Abstract
Embryonic 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.
Source: PLoS One [Open Access]
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003745
Posted by
Robert Karl Stonjek