Evidence of Oxidative Stress in Autism Derived from Animal Models
Xue Ming, Michelle A. Cheh, Carrie L. Yochum, Alycia K. Halladay and George C. Wagner
DOI : 10.3844/ajbbsp.2008.218.225
American Journal of Biochemistry and Biotechnology
Volume 4, Issue 2
Autism is a pervasive neurodevelopmental disorder that leads to deficits in social interaction, communication and restricted, repetitive motor movements. Autism is a highly heritable disorder, however, there is mounting evidence to suggest that toxicant-induced oxidative stress may play a role. The focus of this article 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.
© 2008 Xue Ming, Michelle A. Cheh, Carrie L. Yochum, Alycia K. Halladay and George C. Wagner. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.