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13:11
Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
Michael K Skinner1, Matthew D Anway, Marina I Savenkova
1Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington, USA. Skinner@mail.wsu.edu
Plos One
|November 19, 2008
Summary
Embryonic exposure to vinclozolin, an endocrine disruptor, causes epigenetic changes in the germline, leading to transgenerational effects on the brain transcriptome and behavior in adult offspring. These sex-specific brain alterations may influence the risk of developing brain diseases.
Area of Science:
- Environmental Epigenetics
- Neuroscience
- Toxicology
Background:
- Embryonic exposure to endocrine disruptors can induce epigenetic reprogramming.
- Vinclozolin exposure is known to cause transgenerational effects on the male germline.
- Transgenerational impacts on brain development and function are not fully understood.
Purpose of the Study:
- To investigate the transgenerational effects of embryonic vinclozolin exposure on the brain transcriptome.
- To determine sex-specific alterations in the brain following transgenerational exposure.
- To correlate brain changes with behavioral modifications in offspring.
Main Methods:
- Embryonic exposure of rats to vinclozolin.
- Transcriptome analysis of hippocampus and amygdala in F3 generation offspring.
- Behavioral testing for anxiety-like behaviors.
- Analysis of gene sets and signaling pathways.
Main Results:
- Reproducible, transgenerational changes in brain gene expression were observed in F3 offspring.
- Distinct sex-specific alterations in the hippocampus and amygdala transcriptomes were identified.
- Vinclozolin exposure altered genes involved in axon guidance and long-term potentiation.
- Males showed decreased anxiety, while females showed increased anxiety-like behavior.
Conclusions:
- Embryonic endocrine disruptor exposure can epigenetically reprogram brain development across generations.
- Transgenerational, sex-specific brain alterations correlate with behavioral changes.
- These findings highlight environmental and epigenetic influences on the etiology of brain diseases.
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