Mechanisms underlying brain programming by early-life adversity and nutrition

Experiences during the sensitive period of early-life can “program” peripheral and central biological systems for life. When early in life an individual encounters extreme forms adversities (ELA; e.g. growing up during a war, parental death, abuse or neglect) this can ultimately lead to an increased risk for mental and metabolic disorders, such as depression or obesity. During these early periods nutrition is key for optimal brain development, due to the tremendous growth of the brain and its consequent need for sufficient nutrients. Unfortunately, prevention of ELA is often difficult and we currently lack effective strategies for intervention. Therefore we aimed to understand the role of early nutrition in programming by ELA and whether this can be a suitable target for prevention/intervention strategies to mitigate the ELA-induced increased risks for pathologies. In particular, dietary omega 3 polyunsaturated fatty acids (PUFAs) are important for the brain; they are necessary for normal brain development, have a positive influence on cognition and have anti-inflammatory properties.
In this thesis, we addressed several biological mechanisms that underlie brain programming by ELA as well as by early dietary PUFAs, these include: HPA axis signaling, inflammation and microglia, neuronal/hippocampal plasticity, microRNAs and transcriptomics, brain lipids and oxylipins and lastly the gut microbiota. Based on our work and those of others it becomes more and more evident that an individual exposed to ELA has a different ‘biological make up’, which likely contributes to the ELA-induced increased risk to develop mental and metabolic disorders later in life. Increased understanding of these mechanisms and their interactions will aid the development of effective personalized (nutritional) interventions to hopefully prevent or treat ELA-mediated mental and metabolic disorders.