Epigenetic control of gene transcriptional and behavioural responses to stress in the dentate gyrus

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Stress affects the lives of both humans and animals in our society. Most debilitating for mental welfare and wellbeing in humans is psychological stress, for instance marital problems, job insecurity, and bullying. In farmed and companion animals, examples of psychological stress include overcrowding (e.g. chickens, pigs), long-lasting transports (e.g. cows, sheep, pigs) and abuse. Successful coping with such stressful events involves adaptive and cognitive processes in the brain that make the individual more resilient to repeated stress in the future. Some events, however, are so traumatic that the memories of them become a tremendous burden, leading to psychosomatic and behavioural disturbances and psychiatric diseases (anxiety and depression). To help people to cope with stress in their lives, to develop directives to reduce stress and to improve wellbeing of our companion, farmed and laboratory animals, we need to obtain better insight into how the brain processes stress and creates memories of psychologically stressful events. At present it is unclear how the healthy brain adapts to and learns from stressful events. We have recently discovered that after stress certain molecular processes ("epigenetic modifications") occur in the nucleus of nerve cells which are crucial for the expression of genes necessary for the adaptation of these cells to a stressful event. Our proposal aims to investigate the role of these epigenetic modifications in the regulation of gene expression and the identity of the genes affected by these modifications. Obtaining this information is crucial to understand how nerve cells "learn" from stressful events. Insight into these processes and the function of the genes involved will help to develop new ways to reduce the burden of stress-related disorders in humans and animals.