The Role of Maternal Obesity and Consumption of a Western-style Diet on Offspring Brain Development and Behavior via an Inflammatory Mechanism
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Date
2023-07-06
Authors
Dunn, Geoffrey
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Publisher
University of Oregon
Abstract
Currently almost 1 in every 3 women of childbearing age in the US are classified as obese. Consumption of a diet high in fats and sugars, such as the average American diet, is one of the largest predictors of increased levels of adiposity in an individual. Further, obesity is characterized in part by a low-grade chronic inflammatory state in peripheral circulation. Maternal obesity is a known risk factor for lasting impacts on neurobehavioral development in offspring. We therefore hypothesized that maternal consumption of a Western-Style diet and obesity-induced inflammation disrupts neurodevelopment of the serotonin system in the amygdala, increasing anxiety behaviors in non-human primate offspring. Indeed, our analyses suggest that maternal adiposity levels were associated with decreased offspring serotonin innervation in the amygdala which were associated with increased anxiety behaviors. Further, the number TPH2+ cells in the raphe nuclei, the site of serotonergic neuron cell bodies, were reduced in maternal WSD offspring. These finding suggested that maternal WSD and adiposity were associated with increased anxiety behavior in offspring through disrupting the development of the central serotonergic system during perinatal development.Further examinations of the mechanisms by which maternal WSD and obesity influence offspring neurobehavioral development suggest that obesity-induced inflammation is driving the observed perturbations in the serotonergic system. As the primary immune cell of the central nervous system, microglia play an integral role throughout perinatal neurodevelopment. Quantifying microglial number and morphology in the offspring amygdala suggested that maternal WSD and adiposity levels influenced microglia function throughout both pre and postnatal development. Specifically, maternal WSD appeared to elicit persistent effects on offspring microglia number while levels of adiposity appeared to have a more transient effect in prenatal development. These findings suggest that maternal WSD and obesity may elicit their effects on offspring neurobehavioral development through modulation of microglia during perinatal development.
This dissertation includes previously published and co-authored material.