Sullivan, E. L. | bioRxiv Science

bioRxiv2021

Vertex-wise characterization of Non-Human Primate cortical development with prenatal insights.

Characterization of the interwoven complexities of early cortical thickness development has been an ongoing undertaking in neuroscience research. Longitudinal studies of Non-Human Primates (NHP) offer unique advantages to categorizing the diverse patterns of cortical growth trajectories. Here, we used latent growth models to characterize the trajectories of typical cortical thickness development in Japanese macaques at each cortical surface vertex (i.e. grayordinate). Cortical thickness from 4 to 36 months showed regional specific linear and non-linear trajectories and distinct maturation timing across the cortex. Intriguingly, we revealed a "accumulation/ablation phenomenon" of cortical maturation where the most profound development changes in cortical thickness occur in the accumulation or ablation zones surrounding the focal points (i.e., a center of a delineated regions where cortical thickness is thickest or thinnest) throughout the brain. We further examined maternal diet and inflammation in the context of these typical brain trajectories and known network architecture. A well-controlled NHP model of a maternal "Western-style" diet was used alongside measures of inflammatory cytokine interleukin-6 (IL-6) in the mothers during gestation. We observed that these accumulation and ablation zones of variable change might be most susceptible to environmental effects. The maternal factors, diet and inflammation during pregnancy were distinctively associated with different aspects of offspring cortical development reflected in regions related to distinctive functional networks. Our findings characterize the versatile intricacies of typical cortical thickness development and highlight how the maternal environment plays a role in offspring cortical development.

neuroscience↗

bioRxiv2019

Maternal Obesity and Western-style Diet Impair Fetal and Juvenile Offspring Skeletal Muscle Insulin-Stimulated Glucose Transport in Nonhuman Primates

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a nonhuman primate model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Briefly, adult females were fed a control (CON) or WSD prior to and during pregnancy and lactation. Offspring were weaned to a CON or WSD. Muscle glucose uptake and insulin signaling were measured ex vivo in fetal and juvenile offspring. In vivo signaling was evaluated before and after an intravenous insulin bolus just prior to weaning. We find that fetal muscle exposed to maternal WSD had reduced insulin-stimulated glucose uptake and impaired insulin signaling. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD. Analysis of insulin signaling activation revealed distinct changes between fetal and post-weaning WSD exposure. We conclude that maternal WSD leads to a persistent decrease in insulin-stimulated glucose uptake in juvenile offspring even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not ameliorate the effects of maternal WSD suggesting earlier interventions may be necessary.

physiology↗