Gestational Autoantibody Exposure Alters Early Brain Development in a Rat Model of MAR Autism
Maternal autoantibody related autism (MARA), in which mothers produce specific patterns of autoantibodies during pregnancy, resulting in an autism diagnosis in their offspring, has been observed clinically. Multiple patterns of MARA autoantibodies have been identified clinically, and differences in the severity of the autism phenotype based on the autoantibody pattern have been described. In this study we utilized our preclinical rat model to further elucidate the differential effects of MARA autoantibody exposure based on the known clinical patterns, including the originally identified pattern of lactate dehydrogenase A and B (LDHA/B) + collapsin response mediator protein 1 (CRMP1) + stress-induced phosphoprotein 1 (STIP1) as well as the newly described patterns of CRMP1+CRMP2, CRMP1 + guanine deaminase (GDA), and STIP1+ neuron-specific enolase (NSE). We found that, at postnatal day 2, the levels of brain-specific and serum cytokines/chemokines were altered based on the pattern of MARA autoantibody exposure. Further, we observed changes in the brain transcriptomic profiles that suggest cellular proliferation and differentiation changes due to MARA exposure. Overall design: Seventy-one rat brains were collected at PND 2 and regions containing frontal cortex and hypothalamus were dissected for RNA isolation. Our experiment included 24 control, 12 male and 12 female samples, and 47 MARA samples stratified across 4 autoantibody combinations: 1) CRMP1+CRMP2, 8 samples, 5 males and 3 females; 2) STIP1+NSE, 8 samples, 4 males and 4 females; 3) CRMP1+GDA, 6 samples, 2 males and 4 females; 4) LDHA/B+CRMP1+STIP1, 25 samples, 12 males and 13 females.