Maternal Metabolic Programming of the Developing Central Nervous System: Unified Pathways to Metabolic and Psychiatric Disorders.

The perinatal period presents a critical time in offspring development where environmental insults can have damaging impacts on the future health of the offspring. This can lead to sustained alterations in offspring development, metabolism, and predisposition to both metabolic and psychiatric diseases. The central nervous system is one of the most sensitive targets in response to maternal obesity and/or type 2 diabetes mellitus. While many of the effects of obesity on brain function in adults are known, we are only now beginning to understand the multitude of changes that occur in the brain during development on exposure to maternal overnutrition. Specifically, given recent links between maternal metabolic state and onset of neurodevelopmental diseases, the specific changes that are occurring in the offspring are even more relevant for the study of disease onset. It is therefore critical to understand the developmental effects of maternal obesity and/or type 2 diabetes mellitus and further to define the underlying cellular and molecular changes in the fetal brain. This review focuses on the current advancements in the study of maternal programming of brain development with particular emphasis on brain connectivity, specific regional effects, newly studied peripheral contributors, and key windows of interventions where maternal bodyweight and food intake may drive the most detrimental effects on the brain and associated metabolic and behavioral consequences.