Effects of Social Stress and Obesogenic Diet on Prefrontal Cortex, Hippocampus, and Amygdala Structural Development in Juvenile Female Macaques Público

Kaldas, Andrew (Spring 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/f4752g788?locale=es
Published

Abstract

Chronic stress and obesity are modern epidemics, and together they pose a major public health concern by potential synergistic effects predisposing adverse health outcomes including diabetes, cardiovascular disease, and psychopathologies such as anxiety and depression. There is evidence that social stress and highly caloric diets rich in fats and sugars influence both humans and nonhuman primates, producing similar physiological responses and brain structure alterations. This study examined these effects using a highly translational rhesus monkey model of social stress. Rhesus macaques have comparably complicated brain organizations and social structures as those of humans, without confounding factors such as comorbid psychiatric disorders, drug abuse, cognitive awareness or social stigma. The goal of this study was to use an MRI approach to examine the long-term, potentially synergistic effect of postnatal exposure to social stress and to a highly caloric, obesogenic, diet on brain structure of juvenile female macaques. Regions of interest were the prefrontal cortex, hippocampus and amygdala due to their involvement in stress and emotion regulation and their vulnerability to the effects of stress and obesogenic diets. Measures of cortisol levels, calories consumed, and body weights were collected for examination of associations between these potential underlying biological factors and the brain structural outcomes of chronic exposure to stress and obesogenic diet. To minimize potential confounding effects of prenatal environment or heritability, we used a partial cross- fostering design with random assignment of infants to either a high or low ranking foster mother at birth. MRI techniques were used at 16 months to examine the structural effects of chronic stress and obesogenic diet. This study found increased total brain volume in the obesogenic diet group as well as increased amygdala, hippocampus and prefrontal cortex cerebrospinal fluid volumes in the low ranking group, in comparison to high-ranking animals. These findings suggest that postnatal exposure to a highly caloric diet has long-term global effects on brain size during development while social rank has more region-specific structural effects on the amygdala, hippocampus and prefrontal cortex of female primates.

Table of Contents

Introduction ...................................................................................................1

Methods ......................................................................................................10

Subjects ..........................................................................................................10

Rank Determination...........................................................................................11

Diet Intervention..............................................................................................12

Hair Cortisol Samples.......................................................................................13 Neuroimaging..................................................................................................14

MRI Data Processing, Analysis and Region of Interest (ROI) Volume Computation...............15

Neuroanatomical Definition of Regions of Interest (ROI) in the Atlas................................17

Statistical Analysis...........................................................................................17

Results.........................................................................................................20

Intracranial volume (ICV) .................................................................................20

Total WM, GM, and CSF volume...........................................................................20

Amygdala volume.............................................................................................21

Hippocampal volume........................................................................................21

PFC volume (Total) .........................................................................................21

PFC volume (WM, GM, CSF) ..............................................................................22

Hair Cortisol ...................................................................................................23

Total kcal Consumption ......................................................................................23

LCD kcal Consumption .......................................................................................23

HCD kcal Consumption ......................................................................................24

Body Weight...................................................................................................24

Correlations Between Brain Measures and Cortisol, Feeding and Body Weight Data ............24

Discussion....................................................................................................26

Appendix......................................................................................................36

Fig.1 – AutoSeg UNC-Emory rhesus structural MRI brain atlases ..................................36

Fig. 2 – Images Generated from AutoSeg.........................................................................37

Fig. 3 – Effects of Diet and Rank on ICV ...................................................................38

Fig. 4 – Effects of Diet and Rank on Total WM Volume ................................................39

Fig. 5 – Effects of Diet and Rank on Total GM Volume ..................................................40

Fig. 6 – Effects of Diet and Rank on Total CSF Volume .....................................................41

Fig. 7 – Effects of Diet and Rank on Amygdala Volume.................................................42

Fig. 8 – Effects of Diet and Rank on Hippocampal Volume ...........................................43

Fig. 9 – Effects of Diet and Rank on PFC Total Volume ................................................44

Fig. 10 – Effects of Diet and Rank on PFC WM Volume ................................................45

Fig. 11 – Effects of Diet and Rank on PFC GM Volume ....................................................46

Fig. 12 – Effects of Diet and Rank on PFC CSF Volume. ...............................................47

Fig. 13 –Effects of Diet and Rank on Hair Cortisol ....................................................48

Fig. 14 – Effects of Diet and Rank on Cumulative Kcal Consumption .................................49

Fig. 15 – Effects of Diet and Rank on Cumulative LCD Kcal Consumption ........................50

Fig. 16 – Effects of Diet and Rank on Cumulative HCD Kcal Consumption ........................51

Fig. 17 – Effects of Diet and Rank on Body Weight ......................................................52

Fig. 18 – Table of Correlations ...........................................................................53

Literature Cited.............................................................................................54

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