The stress buffering effects of exercise: How running (literally) from your problems can increase your resistance to life’s stressors

Aggie Mika, 3rd year PhD student in Integrative Physiology

CU undergraduate seniors Sara McConnell and Kristina Hulen work on
their fitness and stress-protective neural circuits while jogging along the
Boulder Creek path. 

Stressful life events can leave an imprint on our physical and psychological health, and can make us vulnerable to psychiatric disorders such as depression and anxiety. However, not everyone who experiences a stressful event ends up developing a psychiatric disorder. Two people can experience the same traumatic life event, such as a natural disaster or loss of a loved one, and have significantly different responses. Some individuals are less affected and can recover quickly, while others seem poorly equipped to cope. Are these individuals simply born with a genetically pre-determined ability to contend with stress, or are there lifestyle and environmental factors that can contribute to an individual’s emotional resilience?

According to more than a decade of collaborative research from CU’s Department of Integrative Physiology and Center for Neuroscience, being physically active can greatly improve how we handle stress. 

Stress is an inevitable part of life. As humans, typical stressors for us might consist of hectic schedules, looming examinations, or other deadlines and pressures associated with school, work and modern life. Experiencing some degree of stress is beneficial; it arouses our minds and bodies and helps us face challenges we may encounter within our environments. For instance, mild nerves accompanied with butterflies in your stomach, an increased heart rate, and slightly sweaty palms before a particularly important exam indicate activation of your stress response, and can help generate a state of increased arousal and attention that will help you perform.

Our body’s immediate response to stressors, often referred to as our fight or flight response, is governed by a set of complex and well-coordinated reactions. This response is largely orchestrated by the sympathetic nervous system, a component of our autonomic, involuntary nervous system, and the hypothalamic pituitary adrenal (HPA) axis, a hormonal cascade initiated by the brain that leads to the release of stress hormones known as glucocorticoids. The sympathetic nervous system consists of nerve fibers that originate within the brain and spinal cord and descend into the periphery, where they connect to almost all of the body’s organs and tissues. Stress-induced activation of these descending nerve fibers accelerates heart rate, dilates pupils, shunts blood flow into the muscles and increases respiration, priming the body to either attack or flee. 

Stressor exposure also triggers the HPA axis, wherein a brain region called the hypothalamus stimulates the pituitary gland to signal to the adrenal gland (a small gland that sits atop the kidney) to release glucocorticoids. When glucocorticoids are released into the circulation, they mobilize the body’s energy reserves from fat stores and muscles, making that energy available for immediate use by the muscles. Together, these systems exquisitely evolved to prepare the body to survive the stressor.

However, repeated exposure to stressors over longer periods of time, or exposure to intense, traumatic stressors can have deleterious consequences on brain health.

Let’s consider repeated stressors first. In our modern lives, these take many forms and can be anything from a long, dreaded morning commute, or regular encounters with a particularly unpleasant coworker. Repeated exposure to stressors has been shown to impair brain function through chronic release of glucocorticoids. Repeated release of glucocorticoids into the brain can remodel connections between brain cells, or neurons, in regions of the brain responsible for learning, memory, attention, and emotion¹. When connections between neurons in these brain regions are altered, it can affect your ability to think, learn, remember, and regulate your emotions.

By engaging in physical activity, we may be able to alter our biology to dampen glucorticoid release, and thus lessen the impact of stress. When you’re exposed to the same stressor on a regular basis, your body’s glucocorticoid response eventually decreases over time—a phenomena termed habituation. CU’s Dr. Serge Campeau and his team have shown that regular exercise can actually speed up this process. Thus, exercising individuals may be able to habituate to repeated stress faster, ultimately decreasing the amount of glucocorticoids allowed to interact with their bodies². This research group has also shown that regular exercise can dampen the release of glucocorticoids following a single exposure to a mild, low intensity stressor³. Milder forms of stress and stressors that are encountered on a regular basis may be less likely to threaten survival, so it’s not necessarily beneficial to mount a full-fledged response after encountering such situations.

But what about more intense stressors? It turns out, exercise doesn’t dampen  glucocorticoid release in response to higher intensity stressors; it only helps constrain stress hormone release to lesser stress, without interfering with an organism’s ability to react to high intensity, potentially dangerous situations. However, even though exercise doesn’t impact the hormonal response to these stressors, research has shown that regular exercise can dampen other consequences associated with high intensity stress.

Indeed, the consequences of an intense stressor go beyond glucocorticoids. Stress researchers have demonstrated that a single experience with an intense, uncontrollable stressor can impact various neurotransmitter systems, i.e. chemicals within the brain that can communicate information between brain cells⁴. Such stressors can interfere with serotonin circuits--neurotransmitter circuits that play a role in mood and emotional behavior. When serotonin systems are altered by stress, it can lead to anxiety, learning deficits, and depression-associated behaviors.

Intense stressors can potently activate the dorsal raphe nucleus (DRN), a brain region that produces the majority of the brain’s serotonin. When serotonin-producing cells within the DRN are activated by an intense stressor, they release a tremendous amount of serotonin. Under normal conditions, in order to prevent excess serotonin release, cells within the DRN are equipped with receptors that regulate how much serotonin they can produce. When serotonin levels get too high, these receptors, called 5-HT1a receptors, essentially tell their respective cells to cool it.

However, when an intense stressor causes an incredible, larger than normal serotonin surge, 5-HT1a receptors become desensitized, meaning they can no longer effectively sense and control serotonin levels. This wreaks havoc on serotonin signaling throughout the rest of the brain; DRN cells project to other regions of the brain, and excessive serotonin release from these cells into certain regions can produce anxiety and behaviors associated with depression.

Regular exercise can actually protect against stress-induced anxiety and depression-associated behaviors by altering serotonin circuits to be more resistant to such stressful experiences. CU’s Dr. Monika Fleshner and her team are interested in the stress-buffering effects of exercise, and have studied how exercise can interact with the serotonin system to produce these protective effects. Her research team has demonstrated that regular exercise can increase gene expression of 5-HT1a receptors within the DRN⁵. This means that within physically active organisms, DRN cells may be making more 5-HT1a receptors. More 5-HT1a receptors can help maintain serotonin levels in the face of intense stress, and therefore prevent dysregulated serotonin signaling throughout the brain. As a graduate student in Dr. Fleshner’s lab, this data never ceases to amaze me—moving our bodies can actually change the way our brains function.

Can exercise actually be used to help people already suffering from stress-related psychiatric disorders, such as depression and anxiety? Indeed, there are many clinical research studies that support this claim. One particularly compelling paper stands out—in it, the authors showed that that exercise can be as effective as antidepressant drugs in treating individuals diagnosed with depression⁶. In fact, this paper showed that exercise may contribute to better long-term outcomes when compared to a commonly used antidepressant.

So there you have it—being physically active can protect you from some of the negative consequences associated with life’s stressors. As productive citizens, stress is something we will always have to contend with. When it gets to be too much, what is the solution? Do we quit our jobs, ditch our smart phones and laptops and move to the woods to avoid all that plagues us? In moments of frustration, this irrational thought has crossed my mind. However, this is not logical or feasible for obvious reasons. Finding practical strategies, like daily exercise, that can prevent the negative consequences of stress is a much more realistic solution. 

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Missed the first post in our exercise science series? Check it out here.