Effects of Social Rank and Delayed Puberty on Brain Structural Development of Juvenile Female Rhesus Macaques: Associations with Behavior and Stress Physiology Open Access

Lombardi, Felicia Nicole (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/q237hs48n?locale=en


During adolescence the brain is undergoing growth and remodeling, in parallel with changes in behavior and stress reactivity. Estradiol (E2) has organizational effects on the brain, influencing a broad range of cellular processes that result in gross morphological changes. During this time, changes are also occurring in the individual's social environment as he/she transitions from parental dependence to a more independent state. Non-human primates exhibit a complex social structure characterized by a matrilineal dominance hierarchy, and thus provide an ideal model to study the effects of E2 and social experience on the adolescent brain and the resulting behavioral and physiological changes. Here, we used socially housed female rhesus macaques to investigate the combined effects of delayed puberty, via E2 suppression, and social status in intermediate-ranking animals on brain structural development during adolescence. We focused primarily on prefrontal cortex (PFC), amygdala (AMYG), and temporal-parietal-occipital (TPO) region of the superior temporal sulcus (STS) due to their implications in processing socioemotional stimuli. Structural MRI scans were collected at pre-puberty (22.64 ± 1.19 months) and peri-puberty (32.95 ± 1.15 months) in 21 juvenile female rhesus macaques. One cohort of animals received chronic Lupron injections to delay puberty. We examined volumes of total intracranial volume (ICV), grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF), as well as AMYG, PFC GM and WM, and TPO GM. Measures of stress physiology, and social behavior were collected to identify functional correlates of the brain structural effects. Results showed significant effects of rank on PFC GM, with larger volumes correlating with higher social rank. In addition, suppression of E2 by Lupron treatment resulted in smaller GM and WM volumes, both total and in PFC, as well as in smaller ICV and AMYG volumes, relative to control subjects. In addition, structural changes in GM, total and in TPO, were predictive of behavioral changes, while AMYG and PFC GM were predictive of stress neuroendocrine measures. Altogether, these results provide evidence that intermediate-ranking animals are susceptible to the interactive effects of E2 and social experience that correspond to changes in behavior and stress neuroendocrine function during adolescence.

Table of Contents

Introduction 1

Methods 12

Subjects 12

Social Rank 12

Experimental Procedures 13

Lupron Administration 13

Structural MRI 13

Behavioral Observations 16

Stress Physiology Assessments 16

Statistical Analyses 18

Results 19

Structural MRI Data 19

Total Intracranial Volume (ICV) 19

Total Grey Matter (GM) Volume 19

Total White Matter (WM) Volume 20

Total Cerebrospinal Fluid (CSF) Volume 20

ICV-Corrected Grey Matter (GM) Volume 20

ICV-Corrected White Matter (WM) Volume 21

ICV-Corrected Cerebrospinal Fluid (CSF) Volume 21

Prefrontal Cortex GM Volume 21

Prefrontal Cortex WM Volume 22

Amygdala Volume 22

Temporal-Parietal-Occipital (TPO) Region of STS GM Volume 23

Multiple Regression Analysis 23

Discussion 24

Tables 36

Figures 37

References 55

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