248 Maternal Antibodies to Fetal Brain Neurons and Autism
increased brain growth may be more prominent in frontal lobes, which is the
largest region of the human brain and is the largest among all life forms. The
frontal lobes go through growth and selection processes later and longer than
other areas of the brain. We believe that this region of the brain is most affected
from exposure to synthetic chemicals during the early stages of fetal brain
development. Selective destruction of fetal brain progenitor cells subsequently
leads to the abnormal growth pattern during the first few years of the postnatal
period in ASD children. Dysregulation of frontal lobe progenitor neurons
would result in dysfunction in higher order social communication, emotional
processing, language, and cognition, while regions mediating more low‐level
functions would be relatively spared (Figure 8.4). We have hypothesized that
early rapid growth in ASD is the result of abnormal proliferations of types of
neurons that have replaced the oxytocin‐ and AVP‐ receptor positive neurons
at the early stage of fetal brain development. These replacement neurons infil
trate into the empty regions (small holes) left after the normal neurons have
been killed and they have a higher proliferation rate than the normal neurons
that were killed by neurotoxic chemicals. We are currently working on an
in vitro model to establish this process. This concept is depicted in Figure 8.4.
Some evidence from the most recent studies carried out in mice elucidated a
potential mechanism by which maternal neuroantibodies modify fetal brain
development. In one study, investigators injected specific maternal neuroanti
bodies into the cerebral ventricles of embryonic mice. These injections resulted
in increased cellular proliferation in the subventricular zone, increased size of
adult cortical neurons, and increased adult brain size and weight compared
with animals exposed to antibody from normal mothers with normal children
[13,14]. It should be noted that these studies are in mice and do not perfectly
represent a huge human brain, but they do give us a glimpse into the bigger
brain phenomenon. In another parallel study, the investigators focused on the
behavioral outcomes of the exposed offspring. The offspring injected with
neuroantibodies exhibited increased stereotypic behaviors and altered social
phenotypes observed in the children born to mothers with this brain pattern
reactivity [24]. Of note, it is well documented that maternal antibodies, espe
cially IgG, are able to reach the fetal brain, at least during the early stages of
gestation when the fetal BBB is still under construction [25].Is There a Link between Autoimmunity and Other Forms
of Neurodevelopmental or Neurodegenerative Disorders?
In logical and pure immunological terms, if one attempts to find an association
between autoimmunity and ASD it would be like looking for a needle in a hay
stack. Simply, the phenomenon we described above, where fetal neuroantigens
would leak into the maternal blood and the maternal neuroantibodies would