The Influence of Maternal Metabolic State and Nutrition on Offspring Neurobehavioral Development: A Focus on Preclinical Models

Abstract

The prevalence of both obesity and neurodevelopmental disorders has increased substantially over the last several decades. Early environmental factors, including maternal nutrition and metabolic state during gestation, influence offspring neurodevelopment. Both human and preclinical models demonstrate a link between poor maternal nutrition, altered metabolic state, and risk of behavioral abnormalities in offspring. This review aims to highlight evidence from the current literature connecting maternal nutrition and the associated metabolic changes with neural and behavioral outcomes in the offspring, as well as identify possible mechanisms underlying these neurodevelopmental outcomes. Owing to the highly correlated nature of poor nutrition and obesity in humans, preclinical animal models are important in distinguishing the unique effects of maternal nutrition and metabolic state on offspring brain development. We use a translational lens to highlight results from preclinical animal models of maternal obesogenic diet related to alterations in behavioral and neurodevelopmental outcomes in offspring. Specifically, we aim to highlight results that resemble behavioral phenotypes described in the diagnostic criteria of neurodevelopmental conditions in humans. Finally, we examine the proinflammatory nature of maternal obesity and consumption of a high-fat diet as a mechanism for neurodevelopmental alterations that may alter offspring behavior later in life. It is important that future studies examine potential therapeutic interventions and prevention strategies to interrupt the transgenerational transmission of the disease. Given the tremendous risk to the next generation, changes need to be made to ensure that all pregnant people have access to nutritious food and are informed about the optimal diet for their developing child.

Keywords: Animal models; Maternal obesity; Neurodevelopmental disorders; Neuroinflammation; Nutrition; Western-style diet.

Figure 1:

Summary of the major the neurodevelopmental insults observed in models of exposure to a maternal obesogenic diet. Maternal obesity is associated with neurodevelopmental disorders such as ADHD and ASD in humans, both of which have been associated with atypical sensory processing in diagnosed individuals. Neuromolecular changes have been observed in animal models and associated with changes in behavioral performance. It has also been associated with increased emotional and reward sensitivities such as increased intake of rewarding substances.