Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alternations in CNS Development
Annual rept. 15 Sep 2008-14 Sep 2009
ROCHESTER UNIV NY
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Multiple studies have demonstrated that children with autism spectrum disorders ASD have a more oxidized redox status than age-matched controls, and recent studies from project member Dr. S. Jill James PI, Project 1 have demonstrated that such differences are found even in lymphoblastoid cell lines isolated from children with ASD. Project 2 uses mouse strains and CNS precursor cells with intrinsic differences in oxidative status to identify parameters that can be used to prospectively identify individuals with a more oxidized redox status and also to elucidate the cellular consequences of such a status for cells of the developing central nervous system. The first years research has focused on identifying core parameters and vulnerabilities using CNS precursor cells that are known to have intrinsic differences in oxidative status despite being isolated from the same animals, thus focusing analysis on outcomes likely to transcend other strain differences. We have defined multiple parameters that are associated with cell-intrinsic differences in redox status including glutathione status, ATPADP ratios, free Ca levels, and mitochondrial depolarization status and levels of bcl-2, gamma-glutamyl cysteinyl synthetase the rate limiting enzyme in glutathione biosynthesis and superoxide dismutase 1. Redox status is also predictive of vulnerability to tumor necrosis factor-alpha and glutamate, two physiological stressors elevated in cerebrospinal fluid of children with ASD.
- Medicine and Medical Research