The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback
Introduction
Exercise and more generally, physical activity, was found to prevent or improve several physical and mental disorders such as depression, cardiovascular, immunological and metabolic diseases (Ströhle et al., 2007, Hill et al., 2008, WHO, 2010). Many of these diseases are recognized as “distress-related”, implying that chronic stress and/or dysregulations of the stress response are involved in their pathogenesis and progress. Therefore, several authors suggested that reducing stress reactivity may be one key mechanism which mediates the beneficial effects of physical activity on health (e.g. Iwasaki et al., 2001, Gerber, 2008).
Interestingly, exercise shares several characteristics of an acute stressor, requiring haemodynamic, endocrine, and metabolic adaptations to restore homeostasis (Sothmann et al., 1996, Hackney, 2006). Amongst others, the sympathetic nervous system (SNS) and the hypothalamus–pituitary–adrenal (HPA) system are activated in an intensity- and duration-dependent manner (Deuster et al., 1989, Hackney, 2006, Hill et al., 2008, Rohleder and Nater, 2009). On a subjective level however, voluntary exercise is rarely described as a stressor. Instead, several authors ascribe rewarding, anxiolytic and mood-enhancing properties to acute bouts of exercise (Reed and Ones, 2006, Brene et al., 2007, Stranahan et al., 2008, Wipfli et al., 2008). Moreover, regular exercise can buffer the deleterious effects of chronic stress (see Tsatsoulis and Fountoulakis, 2006 for a review). In the context of animal studies, voluntary aerobic exercise has been labelled a “harmless threat to homeostasis” (Stranahan et al., 2008) due to the absence of features characterizing harmful stressors, like force, uncontrollability, and threat.
On this background, the relationship between exercise as a “positive stressor” and other forms of stressors has been investigated. The cross-stressor adaptation hypothesis postulates “[…] that exercise training promotes cross-stressor tolerance by adaptation of the physiological stress response systems […]” (Sothmann et al., 1996). According to this hypothesis, the repeated physiological challenge of exercise should result in adaptations which lead to a reduced sensitivity to subsequent homotypic (exercise) and even heterotypic (other than exercise) stressors. In trained persons, catecholaminergic and HPA responses to absolute (but not relative and maximal) exercise workload are reduced and recovery happens faster, indicating an adaptation to the homotypic stressor (Hackney, 2006, Gerber, 2008).
For heterotypic stressors, evidence is more heterogeneous. Acute exercise was found to reduce self-reported distress and anxiety in response to stressful situations (Rejeski et al., 1992, Taylor, 2000). Additionally, a meta-analysis on 15 randomized-controlled trials concluded that blood pressure responses to a laboratory stressor are attenuated when the stress test was preceded by a moderate-to-high-intensity bout of aerobic exercise (Hamer et al., 2006). For the HPA axis, the acute stress-buffering effect of exercise has not been investigated yet.
Regarding the long-term adaptations following regular exercise, a recent meta-analysis did not replicate earlier findings of lower cardiovascular stress reactivity in trained subjects, but instead reported slightly higher cardiovascular reactivity, but faster recovery (Jackson and Dishman, 2006). Other recent studies however found not only attenuated SNS stress markers, but also lower HPA axis responses to a psychosocial stress test in physically fitter subjects (Rimmele et al., 2009, Martikainen et al., 2013). In rodents, both amplification and attenuation of HPA responses were reported, depending on the nature of the heterotypic stressor (see Stranahan et al., 2008).
Neurobiological mechanisms underlying the observed adaptation of the HPA axis are likely related to negative feedback mechanisms of the HPA axis. Several brain regions with a high density of mineralocorticoid and glucocorticoid receptors are involved in the downregulation of HPA axis activity when cortisol levels are elevated. The paraventricular nucleus (PVN) of the hypothalamus, which initiates the neuroendocrine signalling cascade of the HPA axis, receives mostly inhibitory input from the hippocampus (HC), the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The amygdala (AG), in contrast, exerts mostly excitatory input on the PVN (see Herman et al., 2005). Animal studies found stronger amygdala activation after 8 weeks of voluntary wheel running in rats, which may contribute to higher basal HPA axis activity in trained animals (Burghardt et al., 2006).
Neural after-effects of acute aerobic exercise are probably not restricted to stress or HPA-axis regulation, since previous studies revealed an impact of acute exercise on the dopaminergic reward system in terms of a diminished neural response to the anticipation and feedback of monetary rewards (Bothe et al., 2013).
Besides functional effects, exercise likely affects brain structures at a neurophysiological level. Thus, running was also found to reduce hippocampal mineralocorticoid receptor affinity to corticosterone, without changing the total number of mineralocorticoid and glucocorticoid receptors (Droste et al., 2003). Furthermore, exercise seems to protect hippocampal neurons against cell damage usually caused by high level glucocorticoid exposition (Stranahan et al., 2007).
Human studies mostly focus on psychosocial stress as a model of potentially harmful stress with robust SNS and HPA axis activations. Among standardized stress tests, the Trier Social Stress Test (TSST; Kirschbaum et al., 1993) and the Montreal Imaging Stress Task (MIST; Dedovic et al., 2005) are well established in stress research, combining a cognitive task (mental arithmetics) with socio-evaluative threat components.
Neuroimaging studies using the MIST mostly reported decreased activation of the hippocampus, amygdala, ventral striatum, hypothalamus, dorsal and ventral PFC, orbitofrontal cortices, temporal poles and anterior and posterior cingulate cortices (ACC/PCC) (Pruessner et al., 2008, Dedovic et al., 2009b). This is interpreted as a stress-related deactivation of the limbic system. Moreover, hippocampus and amygdala activations were found to be negatively correlated with the stress-induced cortisol increase (Pruessner et al., 2008, Lederbogen et al., 2011). In contrast, other authors reported higher stress-related brain activity in the right temporo-parietal junction, anterior and posterior cingulate cortices, the bilateral insula and hypothalamus (Lederbogen et al., 2011), pointing to the complexity of the investigated processes and the associated methodical challenges in the investigation of the neural substrates of stress.
The aim of the present study was to investigate the neural mechanisms underlying the acute and long-term stress-buffering effect of aerobic exercise according to the cross-stressor adaptation hypothesis, as well as potential interactions of habitual and acute exercise in humans. We hypothesized that previous aerobic exercise should diminish the subjective and psychoneuroendocrine stress response to the MIST, and alter stress-related neural activations.
For this purpose, we applied the MIST subsequently to 30 min of either moderate aerobic exercise (AER) or “placebo” exercise (PLAC) in highly trained (HT) and sedentary (SED) men.
Section snippets
Participants
Two groups of participants were recruited via announcements at different Berlin universities and an elite sport training centre: sedentary (SED) men who did not exercise at all (<once a week), and highly trained (HT) men who intensively trained an endurance sport at least three times a week (e.g. running, cycling, swimming, rowing or triathlon). Participants with a medium level of physical activity were excluded. The participants had to be non-smokers, aged 20–30, right-handed, normal-weighted
Cortisol and α-amylase responses to the treatment
Changes in α-amylase and cortisol levels over time significantly differed between TREATMENT groups (α-amylase: F(1,32) = 47.077, p < .001, partial η2 = .595; cortisol: F(1,32) = 4.629, p = .039, partial η2 = .126). We found larger α-amylase increases from pre- to post-treatment in the AER group compared to the PLAC group (T(1,34) = 6.933, p < .001). Cortisol levels decreased in the PLAC group, according to the diurnal slope, whereas they remained unchanged in the AER group (T(1,34) = 2.215, p = .034). Moreover,
Discussion
In our study, we found sustained effects of a 30-min aerobic exercise intervention on the cortisol and neural responses to the MIST conducted more than 90 min later: (i) AER induced HPA and SNS activation and increased positive mood. (ii) Participants of the AER group showed lower cortisol responses to the MIST and a higher sustained brain response in the bilateral hippocampi. (iii) Participants of the PLAC group showed a stronger brain response in the right dlPFC, dmPFC, IFG, bilateral pre- and
Conclusion
Taken together, our results suggest that 30 min of aerobic exercise are related to a blunted cortisol response to a subsequent psychosocial stressor. Mechanisms underlying this stress-buffering effect are the feedback inhibition of the HPA system and an exercise-induced increase in positive affect.
Role of the funding sources
This study was supported by a PhD scholarship from the Charité – Universitätsmedizin Berlin to Elisabeth Zschucke.
Conflict of interest
None declared.
Acknowledgement
We would like to express our gratitude to Clemens Kirschbaum whose lab performed the analyses of the saliva samples, and to Nina Bothe, Claudia Lange and Sophie Steffens for their assistance with the data acquisition.
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