Chronic Social Stress and Consumption of an Obesogenic Diet Alter Neurobehavioral Development in Infant and Juvenile Macaques Open Access

Kyle, Margaret (Spring 2019)

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As the United States faces a pediatric obesity crisis, it is vital that we understand how children with early exposure to highly caloric diets are developmentally impacted. Obesogenic diet consumption is often comorbid with chronic psychosocial stress, which itself poses a cumulative risk factor for obesity and is associated with psychopathology. It is not well understood, though, how neurobehavioral alterations caused by chronic stress emerge during development and interact with consumption of obesogenic diets. This study examined the potential synergistic impact of postnatal exposure to chronic stress and obesogenic diets on infant and juvenile brain development longitudinally, while probing underlying biological mechanisms. We utilized a translational macaque model of social subordination stress, and followed forty-one (n=21 dominant, n=20 subordinate) rhesus monkeys with access to either a low-calorie diet (LCD) only, or to both the LCD and an obesogenic, highly caloric diet (HCD; Choice condition) from birth. Food intake was recorded continuously using automatic feeders and radio-frequency identification (RFID) chips implanted in subjects’ wrists. Brain structural MRI data was collected during infancy (2 weeks, 6 months) and in the juvenile period (16 months). Hair cortisol, C-reactive protein (CRP), body weight, and kilocalorie (Kcal) consumption data was analyzed across the same period to examine stress- and diet-induced alterations of physiological markers. Subordinate animals had higher CRP levels, and subjects with access to a HCD consumed an increasing number of HCD Kcals with age and consumed more total Kcals than LCD subjects, but there were no group differences in body weight. Females who consumed the HCD showed larger overall brain (intracranial volume; ICV), prefrontal cortex (PFC), insula (INS), and amygdala (AMYG) volumes than those on the LCD. Subordinate animals showed larger AMYG, PFC, and hippocampus (HIPP) volumes than dominants, and AMYG growth was predicted by CRP exposure. Total Kcal consumption predicted ICV, HIPP, and PFC growth rates, while HCD Kcal consumption predicted PFC and INS growth rates. Our findings suggest that postnatal exposure to social subordination and an obesogenic diet has both global and region-specific, non-synergistic effects on primate brain development that appear during infancy and are driven by inflammation and Kcal consumption.

Table of Contents

Table of Contents

Introduction 1

The Developmental Impact of Obesogenic Diets and Chronic Social Stress 1

Chronic Activation of the Autonomic and Endocrine Stress Responses 4

Rhesus Macaque Model of Social Subordination Stress 8

Aims and Hypotheses 10

Methods 12

Subjects 12

Dam Selection and Prenatal Diet Conditions 12

Infant Assignment to Experimental Group and Cross-Fostering 13

Diet Intervention 14

Body Weight Measurements 15

Physiology Measures 15

Inflammatory marker: C-reactive Protein 15

Stress marker: Hair Cortisol Accumulation 16

Structural MRI 17

MR Image Acquisition 17

sMRI Processing 18

Statistical Analysis 20

Linear Mixed Models (LMM) for sMRI Data 21

LMM for Biological Signal Data 22

Results 24

Structural MRI Linear Mixed Models (LMM) 24

Intracranial Volume (ICV) 24

Amygdala 24

Hippocampus 25

Prefrontal Cortex 25

Insular Cortex 26

Biological Signals LMM 27

Inflammatory marker: C-reactive Protein 27

Stress marker: Hair Cortisol Accumulation 28

Body Weight 28

Kcal Consumption 29

Hierarchical Regression Model: Biological Predictors of Brain Growth 29

Results: Biological Predictors of Brain Growth 30

Discussion 32

Tables 46

Figures 53

References 68

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