Effects of Social Rank and Delayed Puberty on Brain Structural Development of Juvenile Female Rhesus Macaques: Associations with Behavior and Stress Physiology Público
Lombardi, Felicia Nicole (2016)
Abstract
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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