Moving Towards Brain Resilience in the face of stressors

By Alfonso Abizaid

Stress is inevitable and a critical factor associated with chronic disorders that include cardiovascular disease, cancer, metabolic disorders, and psychiatric disorders(1). Of the latter, stressors play an important role on the etiology, progression and treatment prognosis(2, 3). Because of this, it is critical to determine the factors that make individuals more resilient against the effects of stressors. One such factor is physical activity, a clearly impactful and cost-effective behavioral change alternative that increases stress resilience, improves mental health treatments, and ultimately reduces the burden on the health care system(4). Yet, despite these obvious benefits, little is known about the biological mechanisms underlying the impact of physical activity on stress resilience, and how psychosocial factors can influence these processes. Finally, and despite reports indicating that Canadian children and emerging adults are not meeting recommended physical activity health guidelines(5), little is known on the consequences of sedentary behaviors on brain function in the short term and in the long term. This might be of special interest to those communities that face barriers to physical activity including children and emerging adults of equity-owed communities including low income, racialized, gender diverse, indigenous or people with special accessibility needs, all communities that are at a higher risk of stress-related mental health challenges.

In this series of blogs we seek to present the latest evidence on the beneficial effects of physical activity on stress induced changes in brain function and mental health disorders with emphasis on building resilience. As part of these blogs we describe the potential long-term consequences of not meeting healthy physical activity recommendations in terms of brain function and vulnerability to stress, and the potential recommendations that could improve engagement in physical activity especially in at risk populations. Knowledge users (scientists, community-based organizations, policymakers, leaders and members of marginalized communities) are invited to participate and communicate some of the gaps that restrict access to physical activity and how programs that are effective in increasing physical activity may alter brain structure while improving mental health indicators. With this interaction we hope to identify research needs related to physical activity as an effective coping mechanism to attenuate the effects of stressors, and to determine interdisciplinary research teams to systematically explore how to improve mental health by improving accessibility to populations that lag behind.  

It is well established that  sufficient physical activity has multiple benefits that promote the health and quality of life. Preclinical studies using animal models show that laboratory animals allowed to run on wheels, or placed in regimens where they must increase their activity show improved metabolic function, improved cognitive function, increased brain plasticity and resilience to stress(6). Human preclinical, clinical, and population-based studies demonstrate that increased physical activity can be an effective intervention to improve metabolic and cardiovascular health, prevent aging-related accidents and improve quality of life in the elderly, promote healthy development in children and emerging adults, and is associated with improved cognitive function, mental health markers, and responses to numerous medical interventions and treatments(7). Importantly, increased physical activity and exercise are thought to be a particularly good interventions to cope with stressors (8).

The effectiveness of physical activity, however, is variable and the factors that can increase or decrease its effectiveness as an intervention to mitigate stress-related health challenges remain to be fully elucidated. At the physiological level, increased physical activity results in metabolic, endocrine, and microbiota changes that can enhance resilience(9). For instance, exercise can diminish circulating inflammatory factors and can influence the release of metabolic hormones that allow organisms to meet the energetic demands of stress more efficiently and with less wear and tear(4, 10). In the brain, increased physical activity promotes the release of neurotropic factors that can increase synaptic plasticity and neurogenesis, and that can also attenuate the negative effects of stress on these parameters (4, 10).

Nevertheless, preclinical models of physical activity have focused on paradigms where laboratory animals are placed in enclosures with activity wheels, which are novel and reinforcing given the generally impoverished environments in which these animals live, suggesting that the beneficial effects are due to a more enriched and stimulating environment rather than the increase in physical activity itself(11). In humans, there is evidence linking chronic stress and impoverished environments with alterations in brain structure, and correlated with deficits in cognitive functions and higher indexes in mental health disorders(3). Similar alteraions have been observed in individuals that follow a sedentary lifestyle(12-14). Importantly, physical activity can also change brain structure in association with improvements in cognitive function(15). Nevertheless, and despite the evidence for direct and indirect benefits of physical activity, equity-owed communities encounter social and economic barriers that make them more reluctant to engage in physical activity opportunities. In fact, a recent report by participACTION, highlights disappointing scores of physical activity in the Canadian population with especially low levels of physical activity in children and emerging adults of equity-owed communities(5, 16). While the long-term effects of these low levels of activity cannot yet be established they do suggest that these young individuals may be less resilient to stressors and at a greater risk of developing mental health disorders. By understanding how physical activity increases resilience against stressors, especially at the level of brain structure and function, we may be able to determine biomarkers to predict resilience, especially after physical activity interventions. Furthermore, forward steps can be made in research to better determine the consequences of sedentary behaviors in equity-owed communities and promote physical activity engagement in to improve resilience and ultimately curb their incidence of mental health disorders in these groups(17).

In the blogs from this special compilation we describe the work of a multidisciplinary group of scientists invited to present at Carleton University’s Neuroscience Colloquium series whose work is focus on this very important issue. We hope that as a knowledge user you find this compilation informative at the personal and professional level and invite you to leave your comments.

Check out this series:

• Community Health and Wellbeing: The Impact of Trauma and Violence Informed Physical Activity (TVIPA)
• Métis Identity and Culture in Health and Wellbeing: An Interview with Dr. Heather Foulds and the Influence of the Red River Jig.
• Navigating the youth mental health crisis: The impact of physical activity and screen time on well-being​​
• Healthy Aging: Benefits of Physical Activity in Populations with Vascular Cognitive Impairments

References

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2. H. Anisman, K. Matheson, Stress, depression, and anhedonia: caveats concerning animal models. Neurosci Biobehav Rev 29, 525-546 (2005).
3. S. J. Lupien, R. P. Juster, C. Raymond, M. F. Marin, The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity. Front Neuroendocrinol 49, 91-105 (2018).
4. B. S. McEwen, The untapped power of allostasis promoted by healthy lifestyles. World Psychiatry 19, 57-58 (2020).
5. N. Kuzik et al., "Lost& Found: Pandemic-Related Challenges and Opportunities for Physical Activity,"  (2022).
6. M. W. Voss, C. Vivar, A. F. Kramer, H. van Praag, Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci 17, 525-544 (2013).
7. P. Posadzki et al., Exercise/physical activity and health outcomes: an overview of Cochrane systematic reviews. BMC Public Health 20, 1724 (2020).
8. M. Pearce et al., Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry 79, 550-559 (2022).
9. L. S. Chow et al., Exerkines in health, resilience and disease. Nat Rev Endocrinol 18, 273-289 (2022).
10. B. S. McEwen, In pursuit of resilience: stress, epigenetics, and brain plasticity. Ann N Y Acad Sci 1373, 56-64 (2016).
11. R. Rabadan, M. Ramos-Campos, R. Redolat, P. Mesa-Gresa, Physical activity and environmental enrichment: Behavioural effects of exposure to different housing conditions in mice. Acta Neurobiol Exp (Wars) 79, 374-385 (2019).
12. C. M. Maasakkers et al., Sedentary behaviour and brain health in middle-aged and older adults: A systematic review. Neurosci Biobehav Rev 140, 104802 (2022).
13. E. C. Perez, D. R. Bravo, S. P. Rodgers, A. R. Khan, J. L. Leasure, Shaping the adult brain with exercise during development: Emerging evidence and knowledge gaps. Int J Dev Neurosci 78, 147-155 (2019).
14. L. W. M. Vergoossen et al., Association of physical activity and sedentary time with structural brain networks-The Maastricht Study. Geroscience 43, 239-252 (2021).
15. W. Zhang, C. Zhou, A. Chen, A systematic review and meta-analysis of the effects of physical exercise on white matter integrity and cognitive function in older adults. Geroscience,  (2023).
16. J.-P. Cahput et al., "ParticipACTION Report Card on Physical Activity for Adults,"  (2021).
17. M. Stevens et al., A Social Identity Approach to Understanding and Promoting Physical Activity. Sports Med 47, 1911-1918 (2017).