Papers of the Month
By Sara Amolegbe
Phthalate exposure before birth may hinder brain development
NIEHS grantees found that adult rats exposed to phthalates early in life had a smaller medial prefrontal cortex region of the brain and performed worse on attention-switching tasks than rats who were not exposed. The study provided new evidence of the neurological effects of phthalates, a chemical commonly used in plastics, on a region of the brain important for behavior and cognition.
Throughout pregnancy and lactation, researchers fed female rats a daily mixture of phthalates at two different levels within the range of estimated daily human exposures. Compared with offspring of females not exposed to phthalates, they found the adult offspring of exposed rats had a smaller medial prefrontal cortex that contained fewer neurons and synapses. They also observed a deficit in cognitive flexibility, which is the ability to switch between thinking about two different concepts and to think about multiple concepts simultaneously. Rats with fewer overall synapses were less cognitively flexible than those with more synapses.
According to the authors, the study is unique in demonstrating the effects of early-life exposure to environmentally relevant phthalate levels on cognitive regions of the brain. The effects were independent of sex, which suggests a common neurotoxic effect of phthalates on the developing cortex of both males and females.
Citation: Kougias DG, Sellinger EP, Willing J, Juraska JM 2018. Perinatal exposure to an environmentally relevant mixture of phthalates results in a lower number of neurons and synapses in the medial prefrontal cortex and decreased cognitive flexibility in adult male and female rats. J Neurosci 38(31):6864−6872.
Metabolism disrupted by night-shift sleep patterns
Being awake at night and asleep during the day, such as the pattern that occurs in night-shift workers, may be linked to disruptions in certain metabolites and pathways without affecting the brain’s master clock, according to an NIEHS-funded study.
Using a laboratory-based sleep study, researchers studied differences between night-shift and day-shift sleep patterns of ten men and four women, ages 22 to 34 years. For three days, half the participants had a night-shift sleep pattern and half had a day-shift pattern. Both groups were then kept awake for a full 24 hours, during which they received identical hourly snacks and provided blood samples every three hours.
The research team found only small differences between day-shift and night-shift patterns for the hormones melatonin and cortisol, which are traditional markers of the body’s circadian clock. Of the 135 metabolites measured in blood, 65 of the metabolites had a significant daily rhythm. Of those, 24 showed a 12-hour shift in rhythm for the night-shift pattern after only three days. The metabolites and pathways affected by the night-shift pattern were related to the liver, pancreas, and digestive tract.
According to the authors, these findings suggest that night-shift sleep patterns may lead to differences in some, but not other, biological signals in shift workers’ bodies, which could disrupt metabolism. This may help explain why night-shift sleep patterns have been linked to certain metabolic disorders, such as obesity and diabetes.
Citation: Skene DJ, Skornyakov E, Chowdhury NR, Gajula RP, Middleton B, Satterfield BC, Porter KI, Van Dongen HPA, Gaddameedhi S 2018. Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci U S A 115(30):7825–7830.
Connection between genes, response to environmental chemicals
NIEHS grantees developed a new method to identify individual-level genetic variation in response to chemical exposures. The approach, which linked zebrafish studies and bioinformatic approaches, might help identify new genetic factors that explain differences in chemical sensitivity.
To find chemicals with patterns of differential biological responses, the researchers analyzed high-throughput screening data from zebrafish exposed to thousands of individual chemicals. Instead of focusing on particular compounds, the team looked at individually sequenced zebrafish from a diverse population and sought differences in susceptibility.
The screening data pointed to abamectin, a commonly used antiparasitic, as a candidate chemical in which exposure produced different responses in zebrafish. The researchers generated genome-wide sequence data for individual zebrafish that were susceptible or resistant to effects of abamectin exposure. That data led them to a genetic region known as sox7 that was associated with the gene-environment effect. Targeted follow-up experiments confirmed that the susceptible zebrafish expressed a lower level of the sox7 gene than the resistant individuals.
According to the authors, the approach provided a quick way to sort through the exposome of chemicals and to look for relationships between genetics and environmental exposure, rather than being limited to preselected candidate exposures. The ability to identify individual-level genetic variation that affects response to individual chemical environments may bring new precision to personalized toxicity prediction and understanding of how risk may differ across communities.
Citation: Balik-Meisner M, Truong L, Scholl EH, La Du JK, Tanguay RL, Reif DM 2018. Elucidating gene-by-environment interactions associated with differential susceptibility to chemical exposure. Environ Health Perspect 126(6):067010.
Air pollution deaths linked to more air conditioning use
By 2050, up to 1,000 more deaths per year in the eastern United States may be linked to higher air pollution that stems from increased demand for air conditioning, according to an NIEHS-funded study. The results linked higher air pollution with increased levels of fossil fuels burned at power plants to meet a higher demand for air conditioning as the climate warms.
The researchers combined projections from five computer models to examine the contribution of future air-pollution–related health damage from power plant emissions, with a focus on emissions driven by demand for air conditioning. By incorporating methods to estimate electricity demand, power sector production and emissions, air quality, and adverse health outcomes from air pollution, they compared future climate predictions to the present day climate scenario.
According to their estimates, changes in climate as a whole in the eastern United States could increase premature mortality related to summer air pollution by about 13,000 deaths due to particulate matter, and 3,000 deaths due to ozone. Increased air conditioning, specifically, may account for up to 1,000 of those deaths.
According to the authors, although air conditioning will save lives as heat waves increase in frequency and intensity due to changes in climate, there will be a trade-off in the resulting harm to human health. They add that the findings highlight the need for more energy-efficient air conditioning and increased use of energy sources, such as wind and solar power, to reduce particulate matter emissions.
Citation: Abel DW, Holloway T, Harkey M, Meier P, Ahl D, Limaye VS, Patz JA 2018. Air-quality-related health impacts from climate change and from adaptation of cooling demand for buildings in the eastern United States: An interdisciplinary modeling study. PLoS Med 15(7):e1002599.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)