In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice

Author:

Bagnall-Moreau Ciara,Huerta Patricio T.,Comoletti Davide,La-Bella Andrea,Berlin Roseann,Zhao Chunfang,Volpe Bruce T.,Diamond Betty,Brimberg Lior

Abstract

AbstractThe concept that exposure in utero to maternal anti-brain antibodies contributes to the development of autism spectrum disorders (ASD) has been entertained for over a decade. We determined that antibodies targeting Caspr2 are present at high frequency in mothers with brain-reactive serology and a child with ASD, and further demonstrated that exposure in utero to a monoclonal anti-Caspr2 antibody, derived from a mother of an ASD child, led to an-ASD like phenotype in male offspring. Now we propose a new model to study the effects of in utero exposure to anti-Caspr2 antibody. Dams immunized with the extracellular portion of Caspr2 express anti-Caspr2 antibodies throughout gestation to better mimic the human condition. Male but not female mice born to dams harboring polyclonal anti-Caspr2 antibodies showed abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as repetitive behaviors and impairments in novelty interest in the social preference test as adults. These data supporting the pathogenicity of anti-Caspr2 antibodies are consistent with the concept that anti-brain antibodies present in women during gestation can alter fetal brain development, and confirm that males are peculiarly susceptible.

Funder

American Association of Immunology

The Nancy Lurie Marks Family Foundatin

NIH SIBR

American Autoimmune Related Diseases Association

Barbara Zucker Career Enhancement Award

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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