Structural Effects of Social Stress and Obesogenic Diet on the Female Macaque Brain: A Longitudinal Study from Infancy to Adulthood Open Access

Abstract

A substantial body of literature has demonstrated a consistent link between psychosocial stress and obesity in children, particularly in those from low socioeconomic backgrounds. Despite evidence indicating a complex interplay between stress, dietary habits, and obesity, a comprehensive understanding of the specific versus potentially synergistic effects of obesity and stress on brain structure and function remains limited. Hence, the present study investigates the developmental and long-term brain structure alterations resulting from the interaction between obesity and psychosocial stress. 41 female rhesus macaques (Dominants -DOM-, n=21; Subordinates -SUB-, n=20) were assigned either only low-calorie diet (LCD) or to both high-calorie diet (HCD) and LCD (Choice diet) from birth studied through the juvenile period. After menarche, all subjects were maintained on a LCD-only diet through adulthood. 27 of the original 41 macaques (DOM: n=13, SUB: n=14) were studied in adulthood to investigate the long-term effects of diet and social rank on brain structure. Cumulative Kcal consumption was measured from birth to 6 months and from 6 months to 16 months. Body weights were measured at birth, 2 weeks, 6 months, 16 months, and in adulthood.

Overall, the findings show insult-specific effects of obesogenic diet and psychosocial stress on cortical and corticolimbic brain regions. Animals with access to the obesogenic diet had larger overall brain size (measured as ICV) and larger volumes in the prefrontal cortex and its associated gray matter, insula, superior temporal sulcus, and temporo-parieto-occipital rostral and caudal regions than those in the low-calorie diet. Most of these regional diet effects, except for the insula, were driven by general effects of the diet on brain size. The diet effects were lost when adding the adult data to the longitudinal analysis, suggesting transient effects of obesogenic diets while the animals were consuming it, but not long-term, persistent effects. These findings highlight the potential of brain rescue mechanisms that could offset lasting developmental effects of early-life obesogenic diet consumption. With respect to social rank, SUB exhibited larger volumes in brain regions related to social cognition than DOM animals. When the adult data was added to the longitudinal analysis, the effects of social rank were prominent in the superior temporal sulcus, temporo-parieto-occipital rostral region, and the temporal auditory cortices after ICV data correction, suggesting long-term, persistent and cumulative effects of these social experiences.

Table of Contents

Table of Contents

Introduction 1

The Impact of Psychosocial Stress and Obesogenic on Development 1

The Rhesus Macaque Model of Social Subordination Stress 3

Psychosocial Stress- and Obesogenic Diet-Induced Alterations in Corticolimbic Neurocircuitry 5

Aims and Hypotheses 8

Methods 10

Subjects, Housing, and Experimental Design 10

Diet Conditions 11

Structural MRI (sMRI) Data 12

Regions of Interest (ROIs) 15

Statistical Analysis 16

Results 18

Intracranial Volume 18

Prefrontal Cortex 18

Temporal Visual Lobe 22

Temporal Auditory Lobe 24

Superior Temporal Sulcus and Temporo-Parieto-Occipital Area, Rostral and Caudal 27

Insula 30

Body Weight and Kilocalories Consumed of the LCD and HCD Diets 31

Discussion 32

Diet and Rank Effects 33

Intracranial Volume 34

Insula 34

Prefrontal Cortex 35

Temporal Lobe (Visual and Auditory) 36

Limitations and Future Studies 39

Significance 39

Tables 42

Figures 43

References 63

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Diet Psychosocial Stress Brain Development MRI Nonhuman Primates
Committee Chair / Thesis Advisor	Mar Sanchez, Emory University
Committee Members	Leah Anderson Roesch , Emory University Vasiliki Michopoulos, Emory University Zsofia Kovacs-Balint, Emory University

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