Autism Studies and Related Medical Conditions, January 2009 - TACA

will be to review our animal model of autism and discuss our evidence that
oxidative stress may be a common underlying mechanism of
neurodevelopmental damage. We have shown that mice exposed to either
methylmercury (MeHg) or valproic acid (VPA) in early postnatal life display
aberrant social, cognitive and motor behavior. Interestingly, early exposure to
both compounds has been clinically implicated in the development of autism. We
recently found that Trolox, a water-soluble vitamin E derivative, is capable of
attenuating a number of neurobehavioral alterations observed in mice postnatally
exposed to MeHg. In addition, a number of other investigators have shown that
oxidative stress plays a role in neural injury following MeHg exposure both in
vitro and in vivo. New data presented here will show that VPA-induced
neurobehavioral deficits are attenuated by vitamin E as well and that the level of
glial fibrillary acidic protein (GFAP), a marker of astrocytic neural injury, is altered
following VPA exposure. Collectively, these data indicate that vitamin E and its
derivative are capable of protecting against neurobehavioral deficits induced by
both MeHg and VPA. This antioxidant protection suggests that oxidative stress
may be a common mechanism of injury leading to aberrant behavior in both our
animal model as well as in the human disease state.
Ming, X., T. P. Stein, et al. (2005). "Increased excretion of a lipid peroxidation
biomarker in autism." Prostaglandins Leukot Essent Fatty Acids 73(5): 379-84.
It is thought that autism could result from an interaction between genetic and
environmental factors with oxidative stress as a potential mechanism linking the
two. One genetic factor may be altered oxidative-reductive capacity. This study
tested the hypothesis that children with autism have increased oxidative stress.
We evaluated children with autism for the presence of two oxidative stress
biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-
isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with
autism and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher
in children with autism. The isoprostane levels in autistic subjects were variable
with a bimodal distribution. The majority of autistic subjects showed a moderate
increase in isoprostane levels while a smaller group of autistic children showed
dramatic increases in their isoprostane levels. There was a trend of an increase
in 8-OHdG levels in children with autism but it did not reach statistical
significance. There was no significant correlation between the levels of the
biomarkers and vitamin intake, dietary supplements, medicine, medical
disorders, or history of regression. These results suggest that the lipid
peroxidation biomarker is increased in this cohort of autistic children, especially
in the subgroup of autistic children.
Mutter, J., J. Naumann, et al. (2005). "Mercury and autism: accelerating evidence?"
Neuro Endocrinol Lett 26(5): 439-46.
The causes of autism and neurodevelopmental disorders are unknown. Genetic
and environmental risk factors seem to be involved. Because of an observed
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