Autism is defined by a set of stereotypic and repetitious behavioural patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. This evidence has focused on looking for biomarkers of Hg damage, measurements of Hg exposure, epidemiological data and animal studies. Despite this work there is little to support any underlying mechanisms that may link Hg exposure and the development of autism. Pink disease is a rare idiosyncratic hypersensitivity to mercury and it is considered that people who suffered pink disease as a child represent a small sub-set of the population who are inherently sensitive to Hg.
Objectives:
This study aims to examine the link between mercury sensitivity and the development of autism. This will be achieved by examining the mechanisms of Hg sensitivity between cells derived from autism and pink disease participants. This sensitivity is hypothesised to be the result of dysfunctions in glutathione metabolism and redox function.
This hypothesis will be tested by examining the redox status and antioxidant capabilities between autistic and pink disease participants. The redox status and antioxidant potential will also be examined and compared between pink disease and autism participants upon being challenged with a low dose exposure to mercury (thimerosal and methyl-mercury). This is designed to examine whether or not the antioxidant status of either the pink disease or autism cell lines are affected by environmental insult and if this related to mercury sensitivity.
Methods:
Using immortalised cell lines (LCL) derived from autism and pink disease participants, the redox status (glutathione: oxidised glutathione ratio) was measured using High Performance Liquid Chromatography. The cells’ antioxidant potential was measured by using activity assays kits for the 3 of major antioxidant enzymes: GSH pexioxdase, superoxidase dimutase and catalase.
The redox status, antioxidant potential were also examined and compared upon being challenged with low dose exposures to thimerosal and methyl-mercury. This was designed to examine whether or not the antioxidant status of either pink disease or autism LCL was affected by environmental insult and if this related to mercury sensitivity.
Results:
This study is on-going and the full results will be reported at the conference.
Conclusions:
If our hypothesis is supported then it is expected that the redox status is negatively affected by the Hg exposure to a simular degree in both the pink disease cell lines and autistic cells, when compared to the healthy controls. It is also expected these antioxidant enzymes are under-performing in these two groups, thus reflecting their diminished ability to deal with this toxic insult.
These results may be due to an underlying genetic disposition which affects the ability of GSH to eliminate Hg from the cell, thus increasing the amount of damage it can induce.