The Acute Stress Response in the Multiomic Era

Abstract

Studying the stress response is a major pillar of neuroscience research not only because stress is a daily reality but also because the exquisitely fine-tuned bodily changes triggered by stress are a neuroendocrinological marvel. While the genome-wide changes induced by chronic stress have been extensively studied, we know surprisingly little about the complex molecular cascades triggered by acute stressors, the building blocks of chronic stress. The acute stress (or fight-or-flight) response mobilizes organismal energy resources to meet situational demands. However, successful stress coping also requires the efficient termination of the stress response. Maladaptive coping-particularly in response to severe or repeated stressors-can lead to allostatic (over)load, causing wear and tear on tissues, exhaustion, and disease. We propose that deep molecular profiling of the changes triggered by acute stressors could provide molecular correlates for allostatic load and predict healthy or maladaptive stress responses. We present a theoretical framework to interpret multiomic data in light of energy homeostasis and activity-dependent gene regulation, and we review the signaling cascades and molecular changes rapidly induced by acute stress in different cell types in the brain. In addition, we review and reanalyze recent data from multiomic screens conducted mainly in the rodent hippocampus and amygdala after acute psychophysical stressors. We identify challenges surrounding experimental design and data analysis, and we highlight promising new research directions to better understand the stress response on a multiomic level.

Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

“…From a neuroendocrine point of view, acute stress engages a fast and self-limiting body reaction that implicates the involvement of the stress hormones, cortisol, norepinephrine, and epinephrine, the immune system, and stress-sensitive brain areas, such as the hippocampus. The complex interaction among these factors underlying the so-called “fight or flight response” is a beneficial protective mechanism that prepares the body to react to stressors [ 232 ]. A crucial role in the stress system is played by GCs and the HPA axis.…”

IMVEST, an immersive multimodal virtual environment stress test for humans that adjusts challenge to individual's performance

“…Preclinical work suggests that exposing subjects to acute stress can be an effective probe to deliver biomarkers capable of predicting vulnerability to develop psychopathologies ( Cordero et al, 1998 ; Daskalakis et al, 2016 ; Hodes et al, 2014 ; Nasca et al, 2019 ; Walker and Sandi, 2018 ). In addition, acute stress responses can on their own affect brain function, cognition and behavior ( De Quervain et al, 2016 ; Sandi, 2013 ; Schwabe, 2017 ) and affect numerous body systems ( Floriou-Servou et al, 2021 ; Pfau and Russo, 2015 ). Therefore, progress on understanding how humans respond to stressful challenges acutely is crucial for the advancement of individual and population health ( Allen et al, 2017 ).…”

Chronic adolescent stress increases exploratory behavior but does not appear to change the acute stress response in adult male C57BL/6 mice

“…Ultimately, the goal of animal models in the study of chronic stress is to elucidate the neurobiological mechanisms that underlie stress-related diseases. The stress response is complex, and goes beyond activation of the HPA axis ( Floriou-Servou et al, 2021 ; Joëls and Baram, 2009 ). Unbiased transcriptomic analyses have already highlighted several potential mechanisms responsible for the alterations in behavior associated with chronic stress ( Bagot et al, 2015 , Bagot et al, 2016 ; Gray et al, 2014 ; Nasca et al, 2015 ; Stankiewicz et al, 2015 ; Terenina et al, 2019 ; van der Kooij et al, 2015 ).…”