Joint Press Release by Charité and DZNE
Dysfunctions in the maternal immune system that occur during pregnancy could possibly lead to impaired brain development in the unborn child. This is suggested by studies by Charité – Universitätsmedizin Berlin and the German Center for Neurodegenerative Diseases (DZNE), which are based on laboratory experiments and additional findings in humans. According to these studies, embryonic damage due to autoantibodies could be a previously unnoticed cause of behavioral disorders that occur in diseases such as autism, schizophrenia and ADHD. The research results are published in the journal Annals of Neurology*.
During pregnancy, antibodies from the mother’s blood constantly enter the embryonic circulation via the umbilical cord to protect the developing child from infection. However, not all maternal antibodies are directed against foreign substances and serve to defend from pathogens. Some antibodies – known as autoantibodies – attack the body’s own tissues. They may thus cause damage that can manifest, for example, as autoimmune diseases. Just like the beneficial antibodies, a pregnant woman passes on potentially harmful autoantibodies to her unborn child. This could promote the development of behavioral disorders in the child, as recent studies in animal models suggest. Initial data from studies in humans support these findings.
The current study, led by PD Dr. Harald Prüss of Charité’s Department of Neurology with Experimental Neurology on Campus Charité Mitte and the DZNE’s Berlin site, focused on an autoantibody that targets a specific protein on the surface of brain cells. This molecule, known as NMDA receptor, is essential for the interconnection of neurons and normal brain development. “The NMDA receptor antibody is a relatively common autoantibody. Data from blood donations suggest that up to one percent of the general population may carry this particular autoantibody in their blood. The reasons for this are largely unclear,” notes PD Dr. Prüss. If this autoantibody reaches the brain, serious inflammations can arise. However, most carriers are free of such symptoms because the blood-brain barrier – a filtering tissue that surrounds the brain’s blood vessels – is usually hardly penetrable for antibodies. Unless this barrier is damaged or, as with an embryo in early pregnancy, not yet fully developed.
“We investigated the hypothesis that NMDA receptor antibodies reach the brain of the embryo and cause subtle but lasting impairments during this important phase of brain development,” explains PD Dr. Prüß. Indeed, in mice, large quantities of maternal autoantibodies were found to reach the brain of the embryo. This resulted in a reduction of NMDA receptors, altered physiological functions and impaired neuronal development. The offspring showed abnormalities in behavior and some areas of their brains were smaller compared to healthy animals. “This hitherto unknown form of pregnancy-associated brain diseases is reminiscent of psychiatric disorders caused by rubella or chickenpox pathogens. These types of infections also have a temporary effect on the brain that can have lifelong consequences,” says PD Dr. Prüß.
In humans, initial analyses of data from a group of 225 mothers suggest that these autoantibodies occur more frequently in women who have a child with a neurodevelopmental disorder or psychiatric disease. The mothers seem to be protected by the blood-brain barrier. “Further studies will be needed in order to confirm the link between maternal NMDA receptor antibodies and human psychiatric disorders in humans,” emphasizes PD Dr. Prüß. “However, should future research results confirm our hypothesis, tests for such antibodies in pregnant women would have to be included in prenatal screenings. Where necessary, this would allow to initiate treatments to remove the autoantibodies in order to prevent the child from suffering potentially lifelong adverse health effects.”
The current results may explain why previous studies have failed to demonstrate a clear link between NMDA receptor antibodies and psychiatric diseases such as schizophrenia. In newborns, the antibodies transferred by the mother are broken down within a matter of weeks. Most patients in existing studies were young adults. Therefore, when the testing for these autoantibodies took place, they had long since disappeared.
* Jurek B et al. Human gestational NMDAR autoantibodies impair neonatal murine brain function. Ann Neurol. 2019 Jul 20. doi: 10.1002/ana.25552
Charité – Universitätsmedizin Berlin
Charité – Universitätsmedizin Berlin is one of the largest university hospitals in Europe, boasting approximately 100 departments and institutes spread across 4 separate campuses. The hospital offers a total of 3,001 beds and, in 2018, treated 152,693 in- and day case patients, in addition to 692,920 outpatients. At Charité, the areas of research, teaching and medical care are closely interlinked. With approximately 18,000 members of staff employed across its group of companies, Charité is one of the largest employers in Berlin. In 2018, Charité recorded a turnover of more than €1.8 billion, and set a new record by securing more than €170.9 million in external funding. Charité’s Medical Faculty is one of the largest in Germany, educating and training more than 7,500 medical and dentistry students. Charité also offers 619 training positions across 9 different health care professions.
German Center for Neurodegenerative Diseases (DZNE)
The DZNE researches neurodegenerative diseases with the aim of developing new strategies for prevention, therapy and patient care. The DZNE has ten sites throughout Germany (Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Tübingen, Rostock/Greifswald, Ulm and Witten) and a total of around 1,100 employees. It cooperates closely with universities, their clinics and other partners. The DZNE is a member of the Helmholtz Association.
PD Dr. Harald Prüß
Department of Neurology with Experimental Neurology
Campus Charité Mitte
Charité – Universitätsmedizin Berlin
t: +49 30 / 450 560 399
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