Scientists say they have discovered that mood is influenced by cells from the immune system, which are called to the brain in response to stress, according to a study published in The Journal of Neuroscience.
Researchers from Ohio State University conducted a mouse study in order to find out how stress can lead to changes in mood. The study authors say the findings could help with the development of new drugs for the treatment of mood disorders.
For the study, mice were subjected to stress equal to a person’s response to stress in everyday life.
Male mice were grouped together in order to have time to “establish a hierarchy.” One aggressive male was then introduced to the group for 2 hours, in order to promote a level of stress within the mice.
The researchers say that this process gives them an experience of “social defeat,” which in turn leads to submissive and anxiety-like behavior. Three groups of mice were subjected to this process either one, three or six times, while one group did not go through the stress process.
The groups were then tested for symptoms of anxiety, and the researchers found that the more cycles of this process the mice suffered, the higher the anxiety symptoms.
When monitoring the brain signals of the mice who suffered stress, the scientists discovered that the higher the levels of stress, the higher the levels of immune cells known as monocytes that traveled from their blood to their brains. Monocytes are a type of white blood cell.
Further research showed that the monocytes did not originate in the brain. Instead, they travelled there from the bone marrow.
The findings revealed that when the mouse brains experienced prolonged stress, they sent out signals to the bone marrow. The monocytes “surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus.” The researchers found the presence of the monocytes led to symptoms of anxiety.
John Sheridan, professor of oral biology and associate director of the Institute for Behavioral Medicine Research at Ohio State University, explains:
“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.
In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.”
The researchers say that in previous studies, research showed that cells in the brain called microglia, non-nerve cells that provide structure and act as immune cells, are activated by prolonged stress and are partly responsible for the signals that call monocytes from the bone marrow.
“There are different moving parts from the central and peripheral components, and what is novel is them coming together to influence behavior,” says Jonathan Godbout, associate professor of neuroscience at the university.
The study authors say that although they do not know for certain what happens in the brain from this point, this research may give them an idea.
The monocytes that travel to the brain do not respond to natural anti-inflammatory steroids in the body, the researchers say. The cells also have characteristics that indicate they are in a more inflammatory state, which indicates that “inflammatory gene expression” occurs when the brain responds to stress.
“The monocytes are coming out of the bone marrow and they are not responsive to steroid regulation, so they overproduce proinflammatory signals when they’re stimulated,” Prof. Sheridan explains. “We think this is the key to the prolonged anxiety-like disorders that we see in these animals.”
The researchers warn that their research does not apply to all forms of anxiety, but that their findings pave the way for future research.
Eric Wohleb, postdoctoral fellow at the university, adds:
“Our data alter the idea of the neurobiology of mood disorders. These findings indicate that a bidirectional system rather than traditional neurotransmitter pathways may regulate some forms of anxiety responses.”
“We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”