Summary: Chronic stress during pregnancy can trigger inflammatory immune activity in the brain, potentially creating conditions that increase vulnerability to postpartum depression.
Source: Ohio State University
Chronic stress during pregnancy prompts a neuroimmune response that could alter brain structure and function in ways linked to postpartum depression, according to new animal research.
Researchers at Ohio State University report the first evidence that prolonged stress in pregnancy activates immune signaling inside the brain. This response is unexpected because normal pregnancy typically suppresses immune activity both in the body and in the brain.
The team has been investigating the brain biology underlying postpartum depression by modeling chronic gestational stress in rats. In humans, chronic stress during pregnancy is a known risk factor for postpartum depression, a condition marked by intense sadness, anxiety and exhaustion that can impair a mother’s ability to care for herself and her newborn.
Stress commonly triggers inflammation, and inflammation mobilizes immune cells to limit tissue damage. Based on prior findings of disrupted neuronal signaling in stressed pregnant rats, the researchers suspected brain-resident immune cells—microglia—might be responding to stress and influencing neural circuits tied to maternal behavior and mood.
In unstressed pregnant rats, expected immune suppression remained intact across pregnancy. By contrast, rats exposed to unpredictable, repeated stress throughout gestation showed clear signs of neuroinflammation despite no peripheral immune activation. That pattern suggests a disconnect between immune activity in the body and immune activity within the brain.
“We’re seeing immune signaling in the brain that we wouldn’t expect during a normal pregnancy,” said Benedetta Leuner, associate professor of psychology at Ohio State and lead author. “These neuroimmune changes occur alongside the alterations in neuronal signaling we’ve reported previously, and they may be directly related.” She presented the findings on Oct. 19, 2019 at the Society for Neuroscience meeting in Chicago.
To model chronic pregnancy stress, the researchers exposed pregnant rats to a variety of unpredictable stressors that introduce psychological strain without harming the mother or her offspring. In these stressed animals, assays revealed increased levels of pro-inflammatory molecules in the brain and signs that microglia had become both more numerous and more active.
The team also observed indicators that microglia were interacting with neurons and synapses. In earlier work, Leuner’s lab found that chronic gestational stress prevents the normal, motherhood-related increases in dendritic spines—tiny, hair-like protrusions on neurons that receive synaptic input. Those same stressed rats displayed behaviors resembling human postpartum depression: reduced physical contact with their pups and other depressive-like behaviors.
Building on those findings, the researchers now plan experiments to test whether the activated microglia are responsible for the loss of dendritic spines. One hypothesis is that microglia may be pruning away synaptic material on dendrites, contributing to the structural changes that underlie altered maternal behavior.
Leuner partnered on this research with Kathryn Lenz, assistant professor of psychology at Ohio State, whose work examines how immune mechanisms shape brain development. In prior studies, Lenz and Leuner showed that pregnancy normally reduces microglial numbers in the brain, mirroring the broader immunosuppression that occurs in the body during pregnancy.
“When we overlay chronic gestational stress on a normal pregnancy, the expected immunosuppression in the brain fails to occur,” Lenz said. “Instead we find inflammatory signaling that could be damaging to dendritic spines and synapses. We also see changes in microglial behavior and appetite—every property we have measured in these cells changes with stress.”
The researchers are now developing live-imaging approaches to observe microglia while they engage with synaptic material, and they are manipulating inflammatory pathways in the brain to determine whether reducing neuroinflammation can reverse postpartum depression–like behaviors in the animal model.
“We’ve documented behavioral changes and neural alterations in dendritic spines and synapses, and now we see neuroimmune shifts that implicate microglia as potential contributors to those neural changes,” Leuner said. “Understanding this chain of events could help reveal mechanisms that increase vulnerability to postpartum depression after stressful pregnancies.”
Funding: This research was supported by the National Institutes of Health.
Ohio State contributors to the study included current and former students Caitlin Goodpaster, Nicholas Deems and Rachel Gilfarb.
Source:
Ohio State University
Media Contacts:
Benedetta Leuner – Ohio State University
Image Source:
The image is credited to OSU.
Original Research: The findings were presented at Neuroscience 2019.