The Contribution of Perinatal Nutrition and Inflammation on the Behavioral Regulation of Juvenile Nonhuman Primates

• In Event: 1-021 - Maternal Obesity and Nutrition during Pregnancy: Effects on Offspring Neurobehavioral Development

Integrative Statement

Adverse environmental conditions during early, formative periods of neurodevelopment are associated with a growing number of neuropsychiatric disorders (Kessler, Amminger et al. 2007, Bale, Baram et al. 2010). To varying degrees, maternal diet, metabolic state, and inflammation have each been shown to influence offspring neurodevelopment in humans and in animal models (Van Lieshout and Voruganti 2008, Krakowiak, Walker et al. 2012, Rivera, Christiansen et al. 2015). However, the complex interaction between metabolic, inflammatory, and neural systems makes it difficult to identify targets for intervention. Using a longitudinal non-human primate model of chronic Western-style diet (WSD) exposure, we have previously shown that maternal physiological factors, including third trimester inflammation, uniquely alter offspring behavior. We found that maternal peripheral macrophage-derived chemokine levels predicted impaired juvenile offspring behavioral regulation. This effect was seen independent from the influence of maternal WSD consumption, metabolic state, and offspring diet and sex. The aim of the present study was to examine how perinatal nutrition influences juvenile behavior in light of contributing inflammatory influences. Maternal third trimester and juvenile plasma inflammatory markers were assessed using 29-plex cytokine assay validated for use in non-human primates. Behaviors elicited during temperament assessment were quantified for 11-month old Japanese macaques (Macaca fuscata, n=74) that had been exposed to maternal or post-weaning WSD in a 2x2 factorial design. We used a data-driven approach for inflammatory covariate selection and then characterized the behavioral responses using three-way ANCOVA models for maternal diet, post-weaning diet, and sex. When accounting for the variation present in inflammatory response, offspring which consumed a post-weaning WSD performed fewer engaged behaviors (F1,45 = 4.916, p = .032), and female offspring displayed more withdrawn behaviors (F1,44 = 8.689, p = .005). Ritualized anxiety displays, such as stereotypies, were increased by exposure to either a maternal (F1,45 = 4.203, p = .046), or post-weaning WSD (F1,45 = 6.804, p = .012). High levels of ritualized anxiety behaviors were further associated with low levels of plasma hepatocyte growth factor/scatter factor (HGF-SF) in juveniles (F1,45 = 20.987, p < .001). HGF-SF is involved in GABAergic and dopaminergic interneuron development, showing migratory and inhibitory functions in the developing and adult brain. Despite correlations with peripheral inflammation measures, inflammatory response did not significantly contribute to other behavioral categories. Given the increasing global prevalence of a Western-style diet and neurodevelopmental disorders, these findings can help direct future investigations to alleviate this public health risk.

Authors

• Jacqueline R Thompson, Oregon National Primate Research Center
  Non-Presenting Author

• Hanna C Gustafsson, Oregon Health and Science University
  Non-Presenting Author

• Madison DeCapo, Oregon National Primate Research Center
  Non-Presenting Author

• Jennifer L Bagley, Oregon National Primate Research Center
  Non-Presenting Author

• Damien Fair, Oregon Health & Science University
  Non-Presenting Author

• Elinor L Sullivan, Oregon Health and Science University; Oregon National Primate Research Center; University of Oregon
  Presenting Author