DYSREGULATION OF ENDOGENOUS NITRIC OXIDE EXPRESSION AS RELATED TO AIR POLLUTION AS A RISK FACTOR FOR AUTISM

COPELAND L.^1
1Department of Pediatrics, University of California San Francisco-Fresno Pediatric Residency Program, Fresno, California, USA.

Received : 29-12-2013     Accepted : 21-01-2014     Published : 03-04-2014
Volume : 4     Issue : 1       Pages : 32 - 41
Bioinfo Environ Pollut 4.1 (2014):32-41

The arginine-nitric oxide pathway is likely to be involved in the neuropathophysiology of autism through dysregulation of nitric oxide (NO) expression during fetal development. This in turn would lead to a cascade of cell signaling effects that impact early brain development and nervous system connectivity, leading to an autism phenotype. Chemical pathways involving nitric oxide expression are influenced by other cell signaling mechanisms, such as the MET tyrosine kinase receptor-ligand system, which is associated with a robust genetic finding of over-transmission of the MET "C" allele in multiplex families having more than one child with autism spectrum disorder (ASD). Dysregulation of nitric oxide expression, it is proposed, will be found in children with autism who have inherited the MET "C" allele based on downstream under-activation of Nitric Oxide Synthase (NOS). This will likely be reflected in significantly different levels of nitric oxide metabolites (NOx or nitrites + nitrates) in the blood and the airways of autistic individuals with the MET "C" allele. Since the Nitric Oxide Synthase (NOS) enzymes that produce nitric oxide are potentially sensitive to allosteric feedback, it is further suggested that nitric oxide air pollution may be a potential environmental risk factor for autism in the genetically susceptible fetus.