14 Mar Bacterial Infections in Pregnancy May Lead To Brain Changes in Baby
MedicalResearch.com Interview with:
Dr. Elaine Tuomanen
Elaine Tuomanen, MD
Chair and Full Member
Dept of Infectious Diseases
St Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Tuomanen: While investigating mechanisms of brain repair during infection in a mouse model system, we found that components from the surfaces of bacteria could traffic from the mother to the fetus. The bacterial components moved across the placenta and into the fetal brain. To our surprise, the fetal brain did not respond with neuronal death like we see in children with meningitis. Rather, fetal neurons proliferated. This response involved the innate immune system (TLR2) inducing the neuronal transcription factor, FoxG1, which is known to drive proliferation. The newly born neurons migrated appropriately to the cortical plate, the area on the surface of the fetal brain that forms the cortex, a major part of the adult brain. Although the neurons moved to the right place in the brain, there were too many and they crowded together in the cortex, changing the architecture of the brain. At birth, affected mice seemed to have no abnormalities. However, when we tested if this change in architecture would affect brain function after birth, mice were shown to progressively develop defects in learning, memory and other cognitive functions. This indicates there is a window during pregnancy where components of bacteria from the mother can change fetal brain architecture and subsequent postnatal behavior
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Tuomanen: In humans, there is a known correlation between infection in pregnancy and behavioral disorders after birth, but there is no clear understanding of why. This study suggests a mechanism in which a pregnant mother with a bacterial infection can be a source of signals that change her baby’s brain architecture and its subsequent functional capacity. An example of this would be the treatment of infection in a pregnant woman using the common classes of antibiotics that kill bacteria by releasing these signaling components (e.g. beta lactam antibiotics). We modeled this in mice and found that treatment of maternal infection with ampicillin, which explodes bacteria into signaling pieces, induced abnormal brain architecture in the fetus and behavioral deficits in the newborn pups. At this point, we don’t know if this applies to humans.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Tuomanen: Many questions need to be answered for this new area of maternal-fetal medicine. What kinds and timing of bacterial infection in pregnancy lead to changes in the fetal brain? Are other parts of the brain also affected? Can we block this effect? What are the implications for use of antibiotics in pregnancy? Can examination of outcomes in cohorts of pregnant women link antibiotic treatment of infection to increased incidence of behavioral disorders. Recent links between increased FoxG1 and autism raise the possibility that the mechanisms we have uncovered might relate to this behavioral disorder.
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Citation:
Jessica Humann, Beth Mann, Geli Gao, Philip Moresco, Joseph Ramahi, Lip Nam Loh, Arden Farr, Yunming Hu, Kelly Durick-Eder, Sophie A. Fillon, Richard J. Smeyne, Elaine I. Tuomanen. Bacterial Peptidoglycan Transverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior. Cell Host & Microbe, 2016; 19 (3): 388 DOI: 10.1016/j.chom.2016.02.009
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Elaine Tuomanen, MD (2016). Bacterial Infections in Pregnancy May Lead To Brain Changes in Baby MedicalResearch.com;
Last Updated on March 14, 2016 by Marie Benz MD FAAD