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Prenatal Exposure to Autism-Specific Maternal Autoantibodies Impairs Proliferation of Neural Precursor Cells, Neuronal Morphology and Animal Behavior

Thursday, 2 May 2013: 12:00
Chamber Hall (Kursaal Centre)
V. Martinez Cerdeno, Institute for Pediatric Regenerative Medicine, Sacramento, CA

Autism spectrum disorders (ASD) are a group of etiologically and phenotypically heterogeneous neurodevelopmental disorders manifesting in early childhood, currently estimated to affect 1 in 88 children. ASD is defined by core deficits in communication and reciprocal social interaction, and by the presence of repetitive or stereotypical behavior.  Autoantibodies to fetal brain proteins, described previously by our laboratory, are found exclusively in a sub-population of mothers whose children are diagnosed with autism spectrum disorder.


We show that maternal auto-antibodies interfere with prenatal development of the embryonic cerebral cortex. In previous passive transfer models, the presence of human IgG antibodies directed against fetal brain proteins during gestation has been shown to produce autism-like behavior in the offspring. The next logical step in elucidating the mechanism by which the maternal autoantibodies affect the developing brain was to examine local effects during the embryonic period. We investigated the impact of these autism-specific maternal antibodies on the neurogenic stem cells in the developing brain. We also investigated the impact of maternal autoantibody exposure on the histology, cellular composition, and neuroanatomy of the mature cerebral cortex.


We passively transferred purified human IgGs directly into the cerebral ventricles of mouse embryos during mid-neurogenesis and examined stem cell proliferation at later stages of development.


We found that maternal autoantibodies increased proliferation in the subventricular zone of the embryonic cerebral cortex. We show that the brains of animal prenatally exposed to autism-specific maternal autoantibodies were bigger, weighed more, and that cortical neuron size was significantly increased. Finally, we investigated the effect of in utero exposure to brain-reactive maternal IgG antibodies on social and stereotypical behavior of the offspring.  We show that the anatomical changes in the adult cerebral cortex that were produced by maternal autoantibody exposure are concomitant with changes in the behavior that are associated with the core features of autism. 


In conclusion, we show that exposure to maternal autoantibodies alters the neural precursor cell profile in the embryonic proliferative zones, the morphology of adult neurons in the cortex, and the behavior of adult mice exposed to maternal autoantibodies during prenatal development. We propose that prenatal exposure to maternal autoantibodies may constitute a viable mechanism for one type of previously unrecognized prenatal risk factor for autism spectrum disorders.

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