We all face stressful situations, but we do not all respond the same way. How we respond depends on the situation and differences in our biology. A new study from Canada may help us begin to understand these differences. While studying how mice react to stress, the team may have uncovered why exercise can boost stress resilience.
Stress in the Brain
Stress is a normal response to potential threats. Hormones like cortisol and adrenaline increase when we are stressed, making us more alert and ready to react. However, stress can be harmful over time. Chronic stress weakens the immune system and increases the risk of several conditions including heart disease, anxiety, and depression.
Even short periods of stress can lead to changes in the brain. One area this affects is the blood-brain barrier. The blood-brain barrier is made up of tightly joined cells that line the blood vessels in the brain. It prevents harmful substances like bacteria, toxins, or certain drugs from entering the brain while allowing essential nutrients to pass through.
Stress increases inflammation in the brain, making the blood-brain barrier weaker and more permeable. These changes have been seen in individuals with depression and anxiety disorders. This study suggests that there may be a link between the blood-brain barrier and how we respond to stress.
The team began their study by observing how different mice react to stress. Each mouse was paired with a more dominant, aggressive mouse. For five minutes a day, the mice were
exposed to repeated confrontational encounters with the aggressor mouse. Some mice appeared to be resilient and were able to return to their normal social behaviors after the stressor was removed. However, others struggled to recover, becoming withdrawn, anxious, or even depressed.
Using a microscope to examine their brains, the team found that the stress-resilient mice had something in common. Around the blood-brain barrier, they had higher levels of a protein called endocannabinoid receptor-1 (CB1), the same protein that reacts to cannabis. The brain naturally produces proteins that also bind to these receptors called endocannabinoids. Activating these receptors helps to regulate mood, pain, and appetite. This study seems to suggest that they also influence how we respond to stress.
It was previously thought that these receptors were only found on the surface of neurons. However, the team found endocannabinoid receptors in and around the blood-brain barrier. The resilient mice seemed to have more of this protein in these regions, especially in areas that influence motivation, decision-making, and reward processing. This may be part of the reason why they were more resistant to stress.
Building a Stress-Resilient Brain
Using gene editing technology, the team found that they could boost the expression of this protein in the blood-brain barrier. They created a modified virus that targets and enhances the receptor gene when injected directly into the brain. While this did not affect the animal’s baseline behavior, it did impact how they reacted after encountering the aggressor mouse. The genetically enhanced mice were less anxious overall and seemed to recover from the stressful encounters more quickly.
These findings are markedly similar to the effect that physical exercise can have on stress. Exercise does more than keep our body healthy– it keeps our mind healthy too. It releases endorphins and other neurotransmitters that make us feel good.
In the final part of their study, the team allowed some mice to run on a wheel after each encounter with the aggressor mouse. The more time the mice spent running, the more resilient they seemed to be to stress. Increased running was also associated with enhanced expression of endocannabinoid proteins near the blood-brain barrier. This discovery may be part of the reason why regular exercise not only improves our mood but also guards our brains from stress.
Conclusion
The differences in how we respond to stress may be partially linked to how these proteins influence the blood-brain barrier. However, additional research is needed to understand how the brain changes and copes with stress. The next time you feel stressed or overwhelmed, remember that exercise is one way to protect your brain.
