Accession Number : ADA564808


Title :   Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development


Descriptive Note : Annual rept. 15 Sep 2010-14 Sep 2011


Corporate Author : ROCHESTER UNIV NY


Personal Author(s) : Noble, Mark D


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a564808.pdf


Report Date : Oct 2011


Pagination or Media Count : 21


Abstract : The goals of our work are to develop means of identifying cells, and individuals, that present with a more basal oxidized redox state and to identify molecular mechanisms that functionally integrate such an oxidized state with observations that the multiple environmental insults suggested to be involved in autism pathogenesis also occur in many children that do not develop ASD. This suggests there is an underlying vulnerability phenotype that makes some children more vulnerable to such stressors. The regulatory pathway that we discovered to be central to redox-based modulation of cell division, differentiation and survival affects multiple cellular functions that appear to be related to the pathological changes seen in the CNS of children with autism. Moreover, the integration of these findings with the Nrf2 pathway provides mechanisms that may provide better markers of a more oxidative state and have the added value of explaining why the more oxidized cells of an individual with ASD do not reset themselves to create a normal redox balance. These discoveries provide new targets for resetting these metabolic problems, and continuation of this work looks likely to identify agents that could be used to address the oxidative abnormalities that look increasingly likely to be relevant to the understanding of ASD pathogenesis.


Descriptors :   *ABNORMALITIES , *BEHAVIORAL GENETICS , *BRAIN , *CENTRAL NERVOUS SYSTEM , *OXIDATION , FUNCTIONS , GLUTATHIONE , HIPPOCAMPUS , LYMPHOCYTES , METABOLISM , MODULATION , MOLECULAR PROPERTIES , OXIDATION REDUCTION REACTIONS , PATHOGENESIS , SURVIVAL(PERSONNEL) , TYROSINE , VULNERABILITY


Subject Categories : Linguistics
      Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE