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Environmental Factor, October 2015

Extramural papers of the month

By Nancy Lamontagne

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Researchers pinpoint how mutation increases autism risk

Scientists have identified more than 1,000 gene mutations related to autism, but understanding exactly how they work is elusive. An NIEHS grantee and colleagues have found that one of these mutations affects a biochemical pathway that leads to changes in the brain.

The researchers used human cells and mice to study a gene mutation tied to overexpression of the UBE3A enzyme, which previous studies suggested must be tightly regulated for normal brain development. They discovered that protein kinase A (PKA) normally phosphorylates UBE3A, acting as a master switch to disengage UBE3A from substrates to block its activity. In cells derived from an autism patient, the researchers observed that an autism-linked mutation disrupted this phosphorylation site, leading to enhanced UBE3A activity and excessive development of small protrusions, called dendritic spines, on neurons in the brain. A higher than normal density of dendritic spines has been linked with autism.

Using mice with the same mutation, researchers also found excessive dendritic spine development, which persisted into young adulthood. When they treated neurons with agents that stimulate PKA production, levels of UBE3A decreased. This finding has promising therapeutic implications, since drugs already exist to control PKA.

CitationYi JJ, Berrios J, Newbern JM, Snider WD, Philpot BD, Hahn KM, Zylka MJ. 2015. An autism-linked mutation disables phosphorylation control of UBE3A. Cell 162(4):795-807.

Lung effects from Deepwater Horizon oil burning

The controlled burning of trapped crude oil on the water surface during the 2010 Deepwater Horizon oil spill released numerous pollutants, including particulate matter. A study, partially funded by NIEHS, revealed that acute exposure to the particulate matter from this burning is associated with lung inflammation and exacerbated allergic asthma in mice.

For the study, the researchers used particulate matter collected from controlled-burn plumes. In cell studies, they found that the particulate matter caused toxicity and generated reactive oxygen species and superoxide radicals. Mice exposed to the particulate matter exhibited significant decreases in body weight gain, systemic oxidative stress, and airway inflammation. The researchers also exposed a mouse model of allergic asthma to the particulate matter and found an exacerbated allergic asthma response via increased T helper 2 cells, lung inflammation, and airway mucus production.

These findings provide valuable information for understanding potential health effects in people, especially those with preexisting lung conditions.

CitationJaligama S, Chen Z, Saravia J, Yadav N, Lomnicki SM, Dugas TR, Cormier SA. 2015. Exposure to Deepwater Horizon crude oil burnoff particulate matter induces pulmonary inflammation and alters adaptive immune response. Environ Sci Technol 49(14):8769-8776.

BPA can adversely affect parenting behavior in mice

An NIEHS grantee and colleagues have shown that exposure to the endocrine disruptors bisphenol A (BPA) and ethinyl estradiol can negatively affect parenting behavior in mice. This is one of the first studies to show that endocrine disruptors can influence both maternal and paternal care.

The researchers used the California mouse species, a monogamous species in which both parents care for offspring. They exposed female and male California mice in the womb and during suckling, by feeding their mothers a diet containing BPA or ethinyl estradiol. Control mice received a diet free of endocrine disruptors. Male and female offspring were then randomly paired with breeding partners including both controls and those developmentally exposed to the same endocrine disruptors.

The results showed that female California mice developmentally exposed to either BPA or ethinyl estradiol spent less time suckling their pups. Both parents were also absent from the nest more often if they were exposed to the endocrine disruptors. Even females that were not exposed to endocrine disruptors suckled their pups less and spent more time outside the nest if they were paired with a male that was exposed. The researchers believe this is one of the first studies demonstrating that early exposure of the male partner to an endocrine disruptor can disturb normal patterns of care by both partners.

CitationJohnson SA, Javurek AB, Painter MS, Peritore MP, Ellersieck MR, Roberts RM, Rosenfeld CS. 2015. Disruption of parenting behaviors in California mice, a monogamous rodent species, by endocrine disrupting chemicals. PLoS One 10(6):e0126284.

Warmer days may mean more emergency visits and deaths among all ages

An NIEHS-funded study reports that, in Rhode Island, when maximum daily temperatures rose from 75 to 85 degrees Fahrenheit, heat-related emergency department admissions and deaths increased among people of all ages. The study also suggests that the warmer temperatures forecast for the end of the century could increase emergency department visits and deaths even more.

The researchers conducted a statistical analysis of emergency department visits, deaths, and weather data, taking into account possible confounding factors, such as ozone levels. They found that between 2005 and 2012, an increase in maximum daily temperature from 75 to 85 degrees Fahrenheit, in the period from April through October, was associated with a 23.9 percent higher rate of heat-related emergency visits, which was most pronounced among people ages 18 to 64. The researchers also estimate that if this Rhode Island population were exposed to temperatures projected for 2092 to 2099, there would be 24.4 percent more heat-related emergency department admissions.

The results suggest the need to consider the cumulative benefit of public health educational campaigns and heat warning systems that reflect the potential hazards of even moderate maximum daily temperatures.

CitationKingsley SL, Eliot MN, Gold J, Vanderslice RR, Wellenius GA. 2015. Current and projected heat-related morbidity and mortality in Rhode Island. Environ Health Perspect; doi:10.1289/ehp.1408826 [Online 7 Aug 2015].

(Nancy Lamontagne is a science writer with MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)

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