Nadine Provencal
Max Planck Institute of Psychiatry, Germany
Title: Exposure to early life stress and glucocorticoids: Mechanisms of system-wide epigenetic effects
Biography
Biography: Nadine Provencal
Abstract
Exposure to early life stress (ELS) is a well-known major risk factor for developing psychiatric and behavioral disorders later in life. Both prenatal and postnatal stressors have long-lasting impact on adult pathological states. Epigenetic mechanisms have been shown to be involved in the embedding of these long-term changes. In a model of early life adversity in rhesus macaques, we have shown that differential rearing leads to long-lasting epigenetic alterations in two different tissues, the prefrontal cortex (PFC) and T cells. One of the mechanisms that might lead to these epigenetic alterations in multiple tissues is a long-lasting disruption of the stress hormone system by excessive glucocorticoids (GCs) release after ELS exposure. Using human hippocampal progenitor cells (HPCs), we have recently identified long-lasting DNA methylation alterations induced by GCs exposure, where a significant portion of these marks were initiated early during cellular proliferation and differentiation stages and persisted in mature neurons. Moreover, a significant overlap was observed between our GR-induced epigenetic changes in HPCs and sites previously associated with child abuse in postmortem human hippocampus and blood cells, suggesting similar long-lasting GR-induced epigenetic alterations in the brain and in peripheral tissues reflecting GC actions during ELS. A mechanistic understanding of the long-term epigenetic consequences of stress using a translational approach may allow novel, targeted intervention and prevention strategies for behavioral, psychiatric and other stress-associated disorders.
