Chronic stress during pregnancy triggers an immune response in the brain that can potentially change brain function in ways that can contribute to postpartum depression, new animal studies show.
This study is the first to show evidence of this pregnancy stress response in the brain, which is unexpected because the immune system and brain are suppressed during normal pregnancy.
Researchers from Ohio State University who made the discovery have studied the biology of the brain behind postpartum depression for several years, creating symptoms of depression in pregnant mice by exposing them to chronic stress. Chronic stress during pregnancy is a common predictor of postpartum depression, which is characterized by extreme sadness, anxiety and fatigue that can interfere with a mother's ability to care for herself or her baby.
Stress is known to cause inflammation, which encourages an immune response to protect against the harmful effects of inflammation. Based on what they already know about compromised brain signaling in mice suppressed during pregnancy, scientists suspect immune cells in the brain that respond to stress might be involved. If that is the case, immune changes can create conditions in the brain that increase susceptibility to depression.
In pregnant mice that are not under pressure, normal emphasis on the immune system and brain remains intact during pregnancy. In contrast, stressed mice showed evidence of nerve inflammation. The study also showed that the immune response of stressed mice throughout their body was inactive.
That shows there is a disconnect between what happens in the body and what happens in the brain. "
Benedetta Leuner, professor of psychology at Ohio State and lead author of the study
He speculates that changes in his laboratory signals have been seen before in the brain and that this immune response occurs in parallel, and may be directly related.
Leuner presented the findings on Saturday (October 19, 2019) at the Society for Neuroscience meeting in Chicago.
In this study, rats were exposed to various unexpected and varied stressful events during their pregnancy, a practice that adds to the component of psychological stress but does not endanger the health of the mother or her children.
In stressed animals, the researchers found a number of proinflammatory compounds that indicate an increase in the number and level of activity of primary immune cells in the brain called microglia. Their findings also showed that microglia affected brain cells in the process.
Leuner's Laboratory previously determined in mice that chronic stress during pregnancy prevented an increase in thorns associated with the mother, which is hair-like growth in brain cells used to exchange information with other neurons. These same mice behave in a manner similar to that seen in human mothers with postpartum depression: They lack physical interaction with their babies and show symptoms such as depression.
Leuner and colleagues now plan to see whether brain immune cells activated during pregnancy stress are responsible for the elimination of dendritic spine. They suspected that microglia might clear synaptic material in dendrites.
Leuner has partnered in this study with Kathryn Lenz, assistant professor of psychology at Ohio State, whose work explores the role of the immune system in brain development.
Although pregnancy is known to suppress the immune system, Lenz and Leuner showed in previous studies that the same suppression of the immune system occurs in the brain during pregnancy – the number of microglia in the brain decreases.
"By putting pregnancy pressure on a normal pregnancy, we find that normal immune suppression that should occur during pregnancy does not occur, and there is actually evidence of inflammatory signals in the brain that can have a devastating effect on thorns and synapses," Lenz said. "But we also found changes in microglia tastes. Every characteristic we see in these cells has changed as a result of this stress."
Researchers are now trying to visualize microglia when they do the cleaning to see if they eat synaptic material. They also manipulated inflammatory changes in the brain to see if it reversed behaviors such as postpartum depression in mice.
"We have seen symptoms such as depression and nerve changes in terms of dendritic and synapses, and now we have neuroimmune changes that show that microglia can contribute to nerve changes – which we think ultimately underlies behavior," Leuner said. .