Passive immunization with anti-Myelin-associated glycoprotein antibodies induces an autistic phenotype associated with altered postnatal neurodevelopment

BACAGLIO, CRISTIAN ROMAN; PABLO HECTOR HORACIO LOPEZ; MATTALLONI, MARA; AMAYA VÍCTOR; ANABELA PALANDRI; RONALD L. SCHNAAR

Villa Carlos Paz

Congreso; XXXIV Congreso de la Sociedad Argentina de Neurociencias; 2019

SAN

High titer of anti-Myelin-associated glycoprotein antibodies (anti-MAG mAb) has been observed in infants with autism spectrum disorders (ASDs). We analyzed the possible contribution of MAG to the pathogenesis of ASD by passive immunization with a function-blocking anti-MAG mAb in wild type mice at perinatal stages. Anti-MAG mAb treatment was associated with development of an autistic phenotype characterized by alterations of social interaction and social recognition behaviors, reduced ultrasonic vocalizations and increased stereotyped behaviors with preservation of motor skills. Morphometric stereological analyses showed altered cerebellar neurodevelopment characterized by a transient increase in the number of granule cells at P7 in lobes VI/VII (but not at lobe X) followed by increased neurodegeneration at P14-21. Similarly, we observed a preferential increase of Purkinje cells number in lobes VI/VII characterized by a dystrophic morphology, although their number remained constant along the study. Morphometric studies also identified alterations in cell/size number in prefrontal cortex. MAG-null mice displayed behavioural and neurodevelopmental alterations closely resembling anti-MAG-treated mice. Our results show that blocking MAG function induces phenotypic behaviors and neurodevelopmental alterations associated with ASDs. Altogether, our data supports a pathogenic role of anti-MAG autoantibodies as a leading cause for the development of ASDs in a clinical subgroup.