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TitleAn animal model of autism using GSTM1 knockout mice and early post-natal VPA-treatment
NameYochum, Carrie Leigh (author), Wagner, George (chair), Otto, Tim (internal member), Kusnecov, Alex (internal member), Mirochnitchenko, Oleg (outside member), Rutgers University, Graduate School - New Brunswick,
Degree Date2009-10
Date Created2009
SubjectPsychology,
Autism
DescriptionAutism is a behaviorally defined developmental disorder with unknown origin. However, its etiology most likely involves a gene by toxicant by age of exposure interaction. To test this hypothesis, mouse pups with a deletion of glutathione-S-transferase M1 (a gene associated with increased risk of autism and that codes for an enzyme involved in the management of toxicant-induced oxidative stress) and wild-type controls were exposed to valproic acid (a toxicant known to cause autism-like behavior deficits following prenatal exposure and one that exerts its toxic action, in part, by inducing oxidative stress) on post-natal day 14. It was observed that VPA-treatment resulted in significant increases in the number of cells staining for TUNEL in the hippocampus and cerebellum. There was also a gene by treatment by sex interaction with VPA- treated wild-type females having increased protection against VPA-induced cell death. VPA- treatment also resulted in long-lasting deficits in social behaviors and corresponding changes in brain chemistry. Collectively, these data expand our current animal model of autism by adding a genetic component in the form of an autism susceptibility gene. In addition, these results support the hypothesis that autism may be the result of a gene by toxicant interaction wherein both factors share a common feature of oxidative stress.
NotePh.D.
NoteIncludes bibliographical references (p. 51-61)
Noteby Carrie Leigh Yochum
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051926
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work