Animal Models and Neuroantibodies to Autism 245Further, studies by Fox‐Edmiston et al. [14] described behavioral outcomes
in the children of neuroantibody‐positive mothers. These mothers who had
ASD children also produced antibodies to LDH, STIP1, and CRMP1 antigens.
About 7% of mothers who produced these combined antibodies also had chil
dren with ASD with an increase in stereotypic behaviors in the child.
Maternal neuroantibodies have been associated with the behavioral and
mental deficits that characterize ASD, but because these studies have been
conducted in human participants, it is difficult to determine the mechanism by
which these neuroantibodies lead to ASD. Experimental animal models were
used to decipher if these neuroantibodies play a pivotal role in ASD.
Animal Models and Neuroantibodies to Autism
In order to determine whether maternal neuroantibodies are important in
the development of neurodevelopmental disorders, researchers have utilized
several animal models. The most significant findings are described below.
Rhesus Macaques Model
Rhesus macaques are a very useful animal model to study human neurodevel
opment because of their social repertoire and established battery of social tests
that can objectively measure their behavior. In a study carried out by Martin
et al. [19] in which neuroantibodies were infused into to pregnant rhesus
macaques, the group of monkeys that was exposed through passive transfer to
purified IgG neuroantibodies from mothers of children with ASD had signifi
cantly more ASD stereotypic behaviors and higher levels of motor activity
when placed in an unfamiliar social setting than monkeys treated with IgG
from mothers with normally developing children [20]. Furthermore, these
findings were replicated in a larger study using monkeys who were adminis
tered IgG from mothers of children with ASD specific for the dominant 37‐
and 73‐kDa band pattern (the three combined neuroantibodies that correspond
to LDH, CRMP1, and STIP1). In the macaques model, it was observed that
offspring treated with IgG from mothers of children with ASD exhibited
abnormal social behaviors and, most surprisingly, enlarged brain volume com
pared with control IgG‐treated animals (which were infused with IgG from
normal mothers). It was also found that the pregnant macaques receiving the
ASD‐associated IgG displayed heightened maternal protectiveness toward
their progeny [21]. These studies enhance our insight into the potential mecha
nism by which the maternal neuroantibodies may impart neuromodulation in
developing fetal brains and contribute to ASD. We will come back to the obser
vation of brain enlargement.