Project 2: 'Developmental neurotoxicity: Maternal anti-NMDAR antibodies and fetaldevelopment' (Volpe PI)The clinical literature reports an increased incidence of learning disabilities with children ofpatients with systemic lupus erythematosus (SLE). We have identified a subset of anti-DNAantibodies in lupus patients that cross-reacts with the NMDA receptor (NMDAR). In a mousemodel, the antibodies can cause hippocampal neuronal loss and a memory impairment, orneuronal loss in the amygdala and an emotional disturbance, depending on the agent used tobreach the blood-brain barrier. We have now demonstrated that these antibodies can alterfetal brain development and cause persistent cortical deficits if present in the serum of apregnant mouse. We will confirm these observations using serum from lupus patientsadministered to gestating dams. We will assess whether different monoclonal antibodies toNMDAR mediate different effects. We will determine whether different mouse strains exhibit adifferent vulnerability to antibody-mediated damage. These studies will form the basis for aclinical study in SLE patients and their offspring.
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