1 Submitted: 21 March, 2019; Revised: 3 July, 2019 © Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com. Original Article Predicting stress resilience and vulnerability: brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses Brook L. W. Sweeten, Amy M. Sutton, Laurie L. Wellman and Larry D. Sanford* Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA *Corresponding author. Larry D. Sanford, Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, P. O. Box 1980, VA 23507. Email: SanforLD@evms.edu. Abstract Study Objectives: To examine the rapid eye movement sleep (REM) response to mild stress as a predictor of the REM response to intense stress and brain-derived neurotrophic factor (BDNF) as a potential biomarker of stress resilience and vulnerability. Methods: Outbred Wistar rats were surgically implanted with electrodes for recording electroencephalography (EEG) and electromyogram (EMG) and intraperitoneal Data loggers to record body temperature. Blood was also obtained to measure circulating BDNF. After recovery, rats were exposed to mild stress (novel chamber, NC) and later intense stress (shock training, ST), followed by sleep recording. Subsequently, rats were separated into resilient (Res; n=27) or vulnerable (Vul; n = 15) based on whether or not there was a 50% or greater decrease in REM after ST compared to baseline. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of mild and intense stress to determine if BDNF was predictive of the REM response. Results: REM totals in the frst 4 hours of sleep after exposure to NC predicted REM responses following ST with resilient animals having higher REM and vulnerable animals having lower REM. Resilient rats had signifcantly higher baseline peripheral BDNF compared to vulnerable rats. Conclusions: These results show that outbred rats display signifcant differences in post-stress sleep and peripheral BDNF identifying these factors as potential markers of resilience and vulnerability prior to traumatic stress. Key words: REM; BDNF; stress resilience and vulnerability; PTSD models Signifcance Statement Stress-induced disturbances in sleep have been linked to stress-related disorders, but have been diffcult to examine because of the wide range of effects stress has on sleep as well as individual differences in stress processing. Here we report sleep responses to mild stress are predictive of sleep responses to intense stress, and that baseline circulating brain-derived neurotrophic factor levels correspond with sleep responses to intense stress. This provides potential biomarkers of individual differences in stress responding prior to traumatic stress ex- posure which can provide better models for disorders such as post-traumatic stress disorder. SLEEPJ, 2020, 1–12 doi: 10.1093/sleep/zsz199 Advance Access Publication Date: 26 September 2019 Original Article Downloaded from https://academic.oup.com/sleep/article/43/1/zsz199/5574449 by guest on 25 February 2023