Environmental Factor, March 2011, National Institute of Environmental Health Sciences
Extramural papers of the month
By Jerry Phelps
- Rapid evolution in Hudson River tomcod
- Elevated plasma cytokines in children with autism spectrum disorder
- Glutathione variant linked to lung function growth
- Interactions of lifetime lead exposure and stress
Rapid evolution in Hudson River tomcod
New research findings by NIEHS grantees suggest that Hudson River tomcod have undergone rapid evolution in response to industrial contamination of the river with polychlorinated biphenyls over the last 50 years. Natural selection, the driving process in evolution, usually takes place over thousands of years, but the research team reports that this is the first example in vertebrate animals of such a rapid evolutionary change.
The research team of NIEHS and Superfund Research Program grantees found changes in the gene that codes for the aryl hydrocarbon receptor 2 (AHR2), which is important in mediating toxicity in early life stages. The AHR2 protein in the Hudson River fish is missing two amino acids, which causes a weaker bond between the receptor and PCBs, a necessary step in the metabolism of the compound. The variant is found in about 95 percent of the Hudson River fish and in about 5 percent of tomcod in two smaller streams in Connecticut and on Long Island. The variant can't be found at all in fish further down the Hudson.
Because the Hudson River fish is resistant to the toxic effects of PCBs, they are able to accumulate more of the chemical without becoming sick. However, this evolutionary adaptation is not all good news for the ecosystem. Since the fish can bioaccumulate the compound at higher levels, consumption of them by other fish can lead to transfer of PCBs up the food chain.
Citation: Wirgin I, Roy NK, Loftus M, Chambers RC, Franks DG, Hahn ME(https://www.ncbi.nlm.nih.gov/pubmed/21330491) . 2011. Mechanistic Basis of Resistance to PCBs in Atlantic Tomcod from the Hudson River. Science; doi:10.1126/science.1197296 [Online 17 February 2011].
Elevated plasma cytokines in children with autism spectrum disorder
New research findings report an altered plasma cytokine profile in children with autism spectrum disorders (ASD) compared to typically developing children. Elevated cytokine levels were directly correlated with impaired communication skills and aberrant behavior, and demonstrate that immune alterations in ASD are associated with the severity of the condition.
ASDs are characterized by impairment in social interactions, communication deficits, and repetitive behaviors. These disorders have been on the rise for the past 25 years, but no definitive cause has been found. Cytokines are small cell-signaling proteins that are secreted by glial cells of the nervous system and numerous cells making up the immune system that modulate immune responses.
The authors report a significant shift in cytokine profiles among children with ASD, which suggests that ongoing inflammatory responses may be linked to behavioral disturbances. These findings need to be confirmed in larger studies, but they do suggest that the characterization of immunological markers may have important implications for diagnosis and therapeutic interventions to treat core symptoms and behavioral impairments associated with ASD.
Citation: Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J.(https://www.ncbi.nlm.nih.gov/pubmed/20705131) 2011. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25(1):40-45.
Glutathione variant linked to lung function growth
Scientists at the University of Southern California report that variations in one of four genes in the glutathione metabolism pathway is associated with differences in susceptibility to adverse effects of air pollutants on lung function growth. Glutathione is the most abundant intracellular antioxidant. It is an important defense mechanism in the lung in response to oxidative air pollutants and inflammation.
The gene, known as GSS, codes for glutathione synthetase. Polymorphisms in this gene and others in the pathway have been shown to be associated with reductions in lung function. Variation in GSS was found in 48 percent of the study population of 2,106 children from 12 Southern California cities.
The study results demonstrate that children with GSS variation were differentially susceptible to lung function growth deficits associated with air pollutants including nitrogen dioxide, particulate matter, elemental carbon, organic carbon, and ozone. The authors conclude that these findings place added emphasis on the identification of strategies for reducing levels of urban air pollutants for susceptible populations.
Citation: Breton CV, Salam MT, Vora H, Gauderman WJ, Gilliland FD.(https://www.ncbi.nlm.nih.gov/pubmed/20802163) 2011. Genetic variation in the glutathione synthesis pathway, air pollution, and children's lung function growth. Am J Respir Crit Care Med 183(2):243-248.
Interactions of lifetime lead exposure and stress
Recent laboratory-based research, by NIEHS-supported investigators at the University of Rochester and the Environmental and Occupational Health Sciences Institute, confirms earlier epidemiologic studies that low-level lead exposure and chronic stress interact to cause behavioral and cognitive deficits.
Female laboratory rats were exposed to lead in their drinking water for two months prior to breeding and throughout gestation. At gestation day 16 and 17, some of the pregnant rats were subjected to a restraint stress procedure consisting of three 45-minute sessions. At weaning, offspring pups were provided with unlimited access to food and given the same drinking water regimen that their dams had received. Subsets of the offspring were used for various laboratory tests and some were subjected to a variety of stressors and behavioral tests, including a fixed interval reward test.
Subject data suggest that lead and prenatal stress effects shift high numbers of test subjects towards the high end of the normal range of fixed interval performance values. These findings were consistent with a dose-response type of lead and stress additivity. The authors conclude that altered fixed interval performance represents behavioral inefficiency and possibly dysfunctional energy use.
Citation: Rossi-George A, Virgolini MB, Weston D, Thiruchelvam M, Cory-Slechta DA.(https://www.ncbi.nlm.nih.gov/pubmed/20875452) 2011. Interactions of lifetime lead exposure and stress: behavioral, neurochemical and HPA axis effects. Neurotoxicology 32(1):83-99.
(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)