Project Details
Projekt
Developmental and synaptic defects caused by transplacental transmission of NMDA receptor antibodies
Subject Area
Molecular and Cellular Neurology and Neuropathology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 415914819
Autoantibodies against neuronal proteins interfere with synaptic transmission in the adult brain. In addition, autoantibodies may also have severe impact on the developing brain during pregnancy. Immunoglobulins are actively transported across the placenta, and the immature blood-brain barrier provides access to the developing brain. Indeed, we recently identified five non-encephalitic mothers with serum autoantibodies against NMDA receptors (NMDARs) who delivered babies with neurodevelopmental disorders such as autism, Tourette’s syndrome or attention deficit hyperactivity disorder. In the proposed project, we will address the following questions: 1) Are NMDAR antibodies more common in mothers of children with neurodevelopmental disorders? 2) Can patient-derived monoclonal NMDAR antibodies mimic the phenotype of brain dysfunction in the offspring in a rodent model? 3) How do NMDAR antibodies affect the development of synapses, neuronal networks, and behavior? Using a wide spectrum of epidemiological, behavioral, molecular biological, and physiological techniques, data from this project will answer the question if maternofetal transfer of anti-neuronal autoantibodies is pathogenic by inducing neurodevelopmental defects, which would represent a new class of acquired congenital disorders. Even if this pathogenic link were rare, identification of mothers positive for such antibodies would enable new treatments aimed at preventing antibody transfer and reducing or preventing life-long neuropsychiatric morbidity in the children.
DFG Programme
Research Units
