Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alternations in CNS Development
Abstract
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 year's 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, ATP/ADP 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2009
- Accession Number
- ADA512639
Entities
People
- Mark D. Noble
Organizations
- University of Rochester