The number of children diagnosed with autism spectrum disorder (ASD) is alarmingly high and appears to be continuing to rise. The Centers for Disease Control’s Autism and Developmental Disabilities Monitoring Network estimates that about 1 in 88 children has been identified with an ASD. Despite decades of research the cause of autism is not clear.
A new study published by Shannon Rose, PhD, postdoctoral fellow, and colleagues from the Arkansas Children’s Hospital Research Institute (ACHRI) in PLOS ONE, an international, peer-reviewed, open-access online publication, may provide a clue into the cause of autism in some children on the autism spectrum. The study is titled, “Oxidative Stress Induces Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines in a Well-Matched Case Control Cohort”. Dr. Rose and ACHRI colleagues examined the “powerhouse” of the cell known as the mitochondria. They found that this powerhouse is very sensitive to toxic molecules known as reactive oxygen species in immune cells derived from about one-third of children with autism. When the researchers challenged these sensitive cells with the toxic molecules, their powerhouse, the mitochondria, started to shut down prematurely.
Since these types of toxic molecules can be produced by environmental toxins that have been linked to autism, these researcher hypothesize the mitochondria in a subset of patients with autism could be easily damaged.
This research also explains why obvious genetic abnormalities do not account for the majority of autism cases. Indeed, this research suggests that both genetic and environmental factors combine to result in the development of autism.
In this study, the researchers studied immune cells derived from 25 boys with autism and 25 typically developing boys matched on age. They then systematically increased the level of reactive oxygen species during which they measured the ability of the cells to produce energy and, most importantly, their energy reserves.
Previous studies have suggested that once the energy reserves are depleted in the cell, the cell starts to become non-functional and dies. They discovered that the mitochondria in immune cells from a significant subset – greater than 32 percent – of the children with autism lose their energy reserves when challenged with reactive oxygen species. Reactive oxygen species can be created by immune activation and environmental toxins – two factors that have been closely linked to autism.
The investigators specifically examined mitochondrial reserve capacity, which according to Dr. Rose, “is a measure of the ability of the cell to make more energy in response to a physiological stressor. When cells are stressed by things such as exposures to environmental toxins or by activation of the immune system, they need more energy to survive the harmful conditions created by the stressor.” Compared to cells from unaffected control children, the reserve capacity in immune cells from 32 percent of the children with autism was quickly depleted when the cells were challenged with physiological stress.
According to Richard Frye, MD, PhD, director of autism research at ACHRI, associate professor of Pediatrics at the University of Arkansas for Medical Sciences (UAMS) and second author on the study, “This study not only provides significant understanding into the possible cause of autism in some children but provides insight into potential treatments for children with autism and helps us understand what can be done to protect children during infancy to prevent them from developing autism.”
The research was supported in part by the Jane Botsford Johnson Foundation and the Arkansas Biosciences Institute, the major research component of the Tobacco Settlement Processed Act of 2000.
Oxidative Stress Induces Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines in a Well-Matched Case Control Cohort, Shannon Rose, Richard E. Frye, John Slattery, Rebecca Wynne, Marie Tippett, Oleksandra Pavliv, Stepan Melnyk, S. Jill James, PLOS ONE – Published: January 2014 DOI: 10.1371/journal.pone.0085436