11 - Effects of Early Life Stress on Brain Development and Mental Health

Poster Board Number: 11
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour

Co-authors:

Grace Thompson - University of Arizona - Tuscon; Courtney Miller - University of North Texas Health Science Center; Jamie Choe - University of North Texas Health Science Center; Kate Lesciotto - University of North Texas Health Science Center; Harlan Jones - University of North Texas Health Science Center; Rachel Menegaz - University of North Texas Health Science Center

Abstract Body : One in five Americans struggle with mental illness, including anxiety, depression, and addiction. The presence of these disorders, particularly in adolescents, has been associated with early life stress (ELS). Here, we aim to evaluate how ELS impacts the development of the overall brain and that of specific regions, e.g. the hippocampus. The hippocampus, part of the limbic system, has been indicated in the development of mental illnesses, inhibition of emotional regulation, and behavioral disturbances. We hypothesize that mice which have experienced ELS will have altered brain structure, including decreased hippocampal volume.

Male C57BL/6J mice were raised to postnatal day 21 (P21). Mice were raised under three different early life conditions (n=5/group): (1) typical weaning at P21 (controls); (2) early weaning (EW) at P15; and (3) daily maternal separation (P3-P15) with early weaning at P15 (MSEW). Following sacrifice, whole cranial tissues were fixed and stained with phosphotungstic acid (PTA) following Lesciotto et al. (2020). Tissues were then imaged using a MRS CT-80 micro-CT machine (20 µm³ voxels). 3D Slicer software was used to measure the volume of the brain, its regions (olfactory bulb, cerebrum, cerebellum), and specific structures of interest (hippocampus, thalamus, and hypothalamus). Non-parametric ANOVAs were used to statistically compare volumes among the treatment groups. Because EW and MSEW mice have significantly smaller body masses than control mice, both absolute volumes and scaled volumes were assessed.

Absolute brain volume and regional volume (olfactory bulb, cerebrum, hippocampus, thalamus) were significantly smaller (p< 0.05) in EW and MSEW groups compared to controls. However, when scaled to body size, both EW and MSEW mice had significantly (p< 0.05) larger brain volumes and regional volumes (olfactory bulb, cerebrum, hypothalamus, thalamus) compared to controls. A non-significant trend (p=0.06) was observed for increased relative hippocampal volume in the MSEW and EW mice compared to control mice. No significant difference was found in either absolute or relative overall or regional volumes between the EW and MSEW groups.

ELS has a negative impact on both somatic and brain growth. Increases in relative volumes of brain structures such as the thalamus and hypothalamus in EW and MSEW mice suggests that ELS may result in earlier and/or faster brain growth in these regions. In humans, early development of the limbic system has been theorized to facilitate decision making about threats during early life. A better understanding of how ELS affects brain development will aid in efforts to mitigate the effects of these negative childhood experiences and promote life-long mental health.