CU undergraduate seniors Sara McConnell and Kristina Hulen work on
their fitness and stress-protective neural circuits while jogging along the
Boulder Creek path.
We all know that stress is an inevitable part of life. Typical stressors for us might consist of hectic schedules, looming examinations, or other pressures associated with modern life. Experiencing some degree of stress is good for us; it arouses our minds and bodies and helps us face challenges. For instance, the mild nerves accompanied by butterflies in your stomach, increased heart rate, and slightly sweaty palms before an important exam indicate that your stress response is activated, and helping to arouse your body and mind to help you ace your test.
This is our body’s immediate response to stress. It's often referred to as our fight or flight response; a set of complex and coordinated reactions that our brain initiates when we perceive a challenge or a threat. It's orchestrated by our sympathetic nervous system, which is a system of nerve fibers that starts within our brain and spinal cord and descends all the way down into our bodies, where said nerve fibers connect to almost all of our body’s organs and tissues. When we notice a threat, these nerve fibers send signals to quicken heart rate, dilate pupils and shunt blood flow into our muscles, essentially priming our bodies to either attack or flee. Get it? Fight or flight.
When we see a threat, our HPA axis is also triggered. This is a hormonal response that starts when the brain signals to the adrenal gland (a small gland that sits atop the kidney) to release the stress hormones glucocorticoids. When glucocorticoids are released into our bloodstream, they mobilize our body’s energy reserves from fat stores and muscles, making that energy readily available for immediate use by our muscles, again helping us to attack or flee. Together, these systems evolved to prepare us to survive.
However, being exposed to stressors over longer periods of time, or being exposed to intense, traumatic stressors can have deleterious consequences on our brain health.
Let’s consider repeated stressors first. In our modern lives, these can be anything from the long morning commute, or regular encounters with a particularly unpleasant coworker. Repeated stress can impair brain function through the release of glucocorticoids. Release of glucocorticoids into the brain over and over again 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.
How can we protect ourselves? By exercising, we may be able to alter our biology to decrease glucorticoid release. When you’re exposed to the same stressor on a regular basis, your body’s glucocorticoid response eventually decreases over time—a phenomena called habituation. CU’s Dr. Serge Campeau and his team have shown that exercise can actually speed up this process. So, active people may be able to habituate to stress faster, ultimately decreasing the amount of stress hormones allowed to interact with their bodies2. This research group has also shown that regular exercise can also decrease glucocorticoids after mild, low intensity stress3. Milder forms of stress, especially milder stress that you encounter every day, is less likely to threaten survival, so it’s not beneficial for you to mount a full-fledged response following these situations. Exercise helps your brain control stress hormone release following situations that aren't likely to threaten your survival.
But what about more intense stressors? It turns out, exercise doesn’t dampen glucocorticoid release in response to high intensity stress. This is a good thing, it wouldn't be too great for us if exercise interfered with our ability to react to dangerous situations. However, even though exercise doesn’t impact the hormonal response to intense stress, research shows that exercise can help mitigate other consequences.
Intense, traumatic stressor wreck your body in ways that go beyond stress hormones. Researchers have shown that a single experience with an intense stressor can wreak havoc on various neurotransmitter systems, i.e. chemicals within the brain that can communicate information between brain cells4. Let's focus on serotonin-- a neurotransmitter that plays 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.
How does disrupted serotonin following stress lead to depression and anxiety? Intense stressors can potently activate the dorsal raphe nucleus (DRN), a brain region that houses the majority of the brain’s serotonin. When serotonin-producing cells within the DRN are activated by intense stress, they release a tremendous amount of serotonin—way more than necessary. Under normal conditions, in order to prevent excessive serotonin release, cells within the DRN have receptors that regulate how much serotonin they can produce. When serotonin levels get too high, these receptors, called 5-HT1a receptors, tell their respective cells to cool it.
However, when an intense stressor causes an incredible, larger than normal serotonin surge, 5-HT1a receptors become overwhelmed and are temporarily out of commission. This means that they can no longer control serotonin levels. This wreaks havoc on serotonin signaling throughout the rest of the brain; excessive serotonin release from these cells into other parts of the brain produce anxiety and behaviors associated with depression.
Exercise can actually protect against anxiety and depression associated with stress. CU’s Dr. Monika Fleshner (my boss) and her team (me and some other cool cats) are interested in the stress-protective effects of exercise, and have studied how exercise can change the serotonin system to protect it from stress. Her research team has shown that exercise may be able to increase 5-HT1a receptors within the DRN5. So, after exercise, DRN cells make more 5-HT1a receptors. More receptors means more control over serotonin levels, therefore preventing rampant serotonin throughout the brain.
As a graduate student studying this stuff, this 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 depression and anxiety? There are many clinical research studies that support this. One study 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.
By Aggie Mika
Missed the first post in our exercise science series? Check it out here.