Following on from last Friday’s post on the beneficial effects of stress hormones, we bring you news of study that helps us to better understand the stress process at a cellular level and how stress can lead to mood disorders.
The new research from Ohio State University, published in The Journal of Neuroscience, shows that certain cells from the immune system are recruited to the brain during stress, causing symptoms of anxiety.
Researchers discovered the dynamic mind-body interaction – a two-way communication from the central nervous system to the rest of the body – and back to the central nervous system that ultimately influences behavior during prolonged stress.
Under prolonged stress, the brain sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.
In experiments conducted in mice, researchers showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.
“In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor,” said John Sheridan, senior author of the study. “In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.”
The mice in this study were subjected to stress that might resemble a person’s response to persistent life stressors. In this model male mice were given time to establish a hierarchy, and then an aggressive male was added to the group for two hours. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.
Mice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms. For example, the mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals’ brains from the blood. Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow.
Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don’t respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state.
These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.
These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.
“Our data alter the idea of the neurobiology of mood disorders,” said Eric Wohleb, a pre-doctoral fellow in Ohio State’s Neuroscience Graduate Studies Program. “We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”