Project Details
Projekt
Developmental defects caused by transplacental transmission of autoantibodies against NMDA receptors and further neuronal antigens
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
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 415914819
Autoantibodies against neuronal proteins can interfere with synaptic transmission and excitability in the adult brain. During pregnancy, autoantibodies transported across the placenta and the immature blood-brain barrier may also severely impact the developing brain. In the first funding period, we established a mouse model of maternofetal autoantibody transfer and demonstrated that autoantibodies against the NMDA receptor (NMDAR) subunit NR1 can have short- and long-lasting effects on brain development. Building on this proof-of-concept evidence, we will focus on the following questions in the proposed project: (1) Are autoantibodies against NMDARs and/or other neuronal antigens more common in mothers of children with neurodevelopmental and psychiatric disorders? (2) What are the circuit-level mechanisms by which NMDAR autoantibodies cause neurodevelopmental deficits? (3) Does transplacental transfer of autoantibodies against targets other than NMDARs result in detrimental effects on brain development by following similar pathomechanistic principles? Bringing together clinical cohorts and experimental work in mice, we intend to determine the extent and mechanistic underpinnings of developmental defects in this novel class of disease, which would enable new treatments aimed at reducing or preventing life-long neuropsychiatric morbidity.
DFG Programme
Research Units
