36 Introduction to Autism Spectrum Disorders
Does Brain Size Matter?
Many continue to be blinded by a genetic dogma of autism that presents autism
as an unusual genetic disorder.
To understand how exposure to extremely small amounts of chemicals may
interfere with the normal development of a human fetal brain, we have to avoid
the lure and distraction of looking at mutations that occur as part of normal
development. For example, from the moment of fertilization of a human egg by
a sperm, as each cell divides, random mutations occur which are fixed and inher
ited by daughter cells. Most of these variants have little, if any, physiological
consequence but contribute to genetic diversity within tissues. A small propor
tion will contribute to pathogenic processes such as ASD or other serious disor
ders. Rather, our focus should be on the way the normal branching of the human
brain tree is disturbed by the untimely degeneration of certain cell types that
results in ASD. One approach is to utilize human fetal brain neurons that behave
just like those in a typically developing fetal brain. These cells, known as neuro
blastoma cells, arise from an anomaly in the development of a fetus as a result of
the migration of fetal brain progenitor neurons that settle somewhere in the
body as nonmalignant tumors. These progenitor groups of neurons behave
much like the fetal brain neurons but are disorganized (for further details see
Chapter 7). These neurons often behave like a developing fetal brain. They also
differentiate when prompted by specific neuronal growth hormones; they
respond to mutagenic and neuro‐modifying agents, and exhibit loss or gain of
neuronal receptors similar to human fetal brain stem cells. We decided to use
these neuroblastoma cell lines of male and female origin, and then evaluate if
there are unique or differential responses to exposures of minuscule amounts of
fragrances or testosterone or supernatants from human gut bacteria exposed to
glyphosate. The amount or level of each of the proposed culprits was kept low to
imitate what one would expect to find in the amniotic environment during the
early stages of gestation. For example, in the case of fragrance, we exposed
the neuroblastoma cells to 1:1,000,000 (1 to 1 million) or 1:10,000,000 (1 to
10 million) dilution. The rationale of using such an extremely small amount was
to test the idea that if a pregnant woman was exposed to perfume and inhaled or
applied the perfume on her skin, the absorbed chemicals would be diluted into
six liters of her blood and minuscule amounts would reach the fetus’s brain. This
would imitate the situation of a pregnant woman and the fetus inside her womb.How Autism Develops in a Fetal Brain
Even though no proved neurophysiological biomarker has been associated
with ASD, there have been reports of low plasma oxytocin and arginine vaso
pressin levels. These “twin” nonapeptides are primarily produced within the