244 Maternal Antibodies to Fetal Brain Neurons and Autism
exhibited abnormal brain enlargement when compared with both children
with ASD born to mothers who did not harbor neuroantibodies and normally
developing control children. Further, reactivity to a band near 39 kDa was later
discovered, and paired reactivity to neuroantigens at 39 and 73 kDa correlated
with a broader diagnosis of ASD (which was distinct from full autism at that
time), as well as increased irritability on the Aberrant Behavioral Checklist
scale [19]. We would like to remind readers here that the molecular weight of
one of the most important communication molecules (i.e., oxytocin and AVP
receptors) falls near this range.
Of course, in order to comprehend how these neuroantibodies could poten
tially contribute to the development of ASD one needs to figure out what their
functions are during fetal brain development. Studies by Edmiston et al. (13),
which utilized highly sophisticated analytical tools, determined that the mater
nal neuroantibodies recognize seven developmentally regulated proteins in the
fetal brain that include LDH A and LDH B, stress‐induced phosphoprotein
1 (STIP1), guanine deaminase, collapsin response mediator proteins 1 (CRMP1)
and 2 (CRMP2), and Y‐box binding protein 1 (Figure 8.1). These proteins are
critical for normal brain development. They are necessary for a fetal brain’s
development and play a critical role in neuronal migration and neural network
construction. For example, guanine deaminase has an integral role in dendritic
branching of hippocampal neurons. The hippocampus is an essential part of
the human limbic system and regulates emotions and long‐term memory. It is
good to keep in mind that some ASD children lack both of these normal func
tions. STIP1, in combination with the cellular prion protein, is responsible for
neuritogenesis. Neuritogenesis is a key process in fetal brain growth. This pro
cess is where neurons develop and, more precisely, the individual neurons
sprout out axons from their bodies. These are the main events in neurodevel
opment that create connections between neurons. The sprouting of neurites
(axons and dendrites), which mature into axons and dendrites, is an important
event in fetal brain neuronal differentiation. Studies in living neurons indicate
that neuritogenesis begins immediately after neuronal commitment, with the
activation of membrane receptors by extracellular cues. These receptors acti
vate intracellular cascades that trigger changes in the actin cytoskeleton, which
promote the initial breakdown of symmetry. Then, through the regulation of
gene transcription, and of microtubule and membrane dynamics, the newly
formed neurite becomes stabilized. Any interruption in the molecular machin
ery that regulates the neuritogenesis during initial neurite sprouting can dis
rupt the balance of neurodevelopment. These two proteins also increase
neuronal survival. CRMPs 1–5 are necessary for proper growth of fetal neu
rons and are required for proper cell migration and axon‐dendrite specifica
tion. Y‐box binding protein 1 is involved in almost all DNA‐ and messenger
RNA‐dependent processes and LDH is essential for energy metabolism.