Programming of the brain by early-life stress The impact of early nutritional interventions and later life challenges

Early-life is a critical period for brain development, during which the brain is shaped for life. This ‘programming’ of the brain can be negatively influenced by adversity in the early-life environment, such as abuse and neglect. Early-life adversity can indeed lastingly impact brain structure and function and thereby increase the risk for the development of psychopathologies and cognitive deficits later in life. Extensive literature has shown that ES can induce cognitive dysfunction and alter disease susceptibility in later life. However, the contribution of lifestyle factors and environmental exposure to this ES-enhanced predisposition for psychopathology has only received marginal attention so far. As currently no effective treatments are available, it becomes increasingly important to understand the contribution of adult lifestyle on the increased risk for psychopathology following early-life exposure to stress. Increasing our knowledge on this topic will help to identify vulnerable populations and might contribute to establishing (preventive) therapeutic strategies to improve adult health outcome after ES. Unraveling the underlying biological mechanisms involved in this process is therefore essential. In this thesis, we aimed to gain further insight in the mechanisms underlying ES programming and the contribution of lifestyle or environmental influences to the increased susceptibility to cognitive impairment as a consequence of ES. We here focused on astrocytes and neurogenesis in the hippocampus.