Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress

Mol Psychiatry. 2015 May;20(5):621-31. doi: 10.1038/mp.2014.80. Epub 2014 Aug 5.

Abstract

Traumatic stress in early-life increases the risk for cognitive and neuropsychiatric disorders later in life. Such early stress can also impact the progeny even if not directly exposed, likely through epigenetic mechanisms. Here, we report in mice that the offspring of males subjected to postnatal traumatic stress have decreased gene expression in molecular pathways necessary for neuronal signaling, and altered synaptic plasticity when adult. Long-term potentiation is abolished and long-term depression is enhanced in the hippocampus, and these defects are associated with impaired long-term memory in both the exposed fathers and their offspring. The brain-specific gamma isoform of protein kinase C (Prkcc) is one of the affected signaling components in the hippocampus. Its expression is reduced in the offspring, and DNA methylation at its promoter is altered both in the hippocampus of the offspring and the sperm of fathers. These results suggest that postnatal traumatic stress in males can affect brain plasticity and cognitive functions in the adult progeny, possibly through epigenetic alterations in the male germline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / pathology*
  • Cognition Disorders / etiology*
  • Conditioning, Psychological
  • DNA Methylation / genetics
  • Epigenesis, Genetic
  • Fear / psychology
  • Female
  • Gene Expression
  • Hippocampus / cytology
  • In Vitro Techniques
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Recognition, Psychology
  • Stress Disorders, Traumatic / complications*
  • Stress Disorders, Traumatic / pathology*
  • Swimming / psychology

Substances

  • protein kinase C gamma
  • Protein Kinase C