Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma.
Katharina GappJohannes BohacekJonas GrossmannAndrea M BrunnerFrancesca ManuellaPaolo NanniIsabelle M MansuyPublished in: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2016)
Adverse experiences in early life are risk factors for the development of behavioral and physiological symptoms that can lead to psychiatric and cognitive disorders later in life. Some of these symptoms can be transmitted to the offspring, in some cases by non-genomic mechanisms involving germ cells. Using a mouse model of unpredictable maternal separation and maternal stress, we show that postnatal trauma alters coping behaviors in adverse conditions in exposed males when adult and in their adult male progeny. The behavioral changes are accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus. DNA methylation is also decreased in sperm cells of exposed males when adult. Transgenerational transmission of behavioral symptoms is prevented by paternal environmental enrichment, an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. These findings highlight the influence of both negative and positive environmental factors on behavior across generations and the plasticity of the epigenome across life.
Keyphrases
- dna methylation
- gene expression
- genome wide
- induced apoptosis
- early life
- mouse model
- copy number
- cell cycle arrest
- mental health
- high fat diet
- birth weight
- human health
- sleep quality
- childhood cancer
- depressive symptoms
- endoplasmic reticulum stress
- preterm infants
- signaling pathway
- young adults
- adipose tissue
- pregnancy outcomes
- trauma patients
- climate change
- binding protein
- skeletal muscle
- cell proliferation
- mass spectrometry
- cerebral ischemia
- blood brain barrier
- life cycle
- electronic health record
- pi k akt
- weight gain