Asthma declines with lower power plant emissions

Asthma symptoms and asthma hospitalizations dropped dramatically in response to reduced power plant emissions, according to an NIEHS-funded study. The researchers took advantage of a natural experiment in Louisville, Kentucky, between 2013 and 2016. During that time, nearby power plants either stopped using coal as the energy source or installed better emission controls. This is the first study to link reduced emissions from coal-powered plants with asthma-related health benefits.

The team used dispersion modeling to estimate the movement of sulfur dioxide emissions from the plants and found that exposure decreased after the transition from coal to natural gas and the installation of emission controls. They also demonstrated that these changes were associated with fewer asthma-related hospitalizations and emergency room visits, and reduced use of asthma inhalers.

Specifically, by comparing emissions from the same areas before and after coal retirement, the researchers estimated that energy transitions in the spring of 2015 resulted in 12 fewer hospitalizations and emergency department visits per ZIP code in the following year. Their estimated results translate into nearly 400 avoided hospitalizations and emergency room visits each year across the county. Emission controls installed in 2016 were associated with a 17% drop in asthma inhaler use, and a 32% reduction in odds of using inhalers heavily throughout the month.

Citation: Casey JA, Su JG, Henneman LRF, Zigler C, Neophytou AM, Catalano R, Gondalia R, Chen Y, Kaye L, Moyer SS, Combs V, Simrall G, Smith T, Sublett J, Barrett MA. 2020. Improved asthma outcomes observed in the vicinity of coal power plant retirement, retrofit and conversion to natural gas. Nat Energy 5:398–408.

Glyphosate exposure linked to autism behaviors in mice

A new NIEHS-funded study revealed a possible mechanism by which exposure to the herbicide glyphosate during pregnancy may increase the risk for autism spectrum disorder (ASD) in offspring. According to the study, an enzyme called soluble epoxide hydrolase (sEH) plays a key role in the development of ASD-like behaviors after maternal glyphosate exposure. The sEH enzyme, which helps to break down polyunsaturated fatty acids, has been shown to be involved in other neurodevelopmental disorders related to inflammation.

The team exposed pregnant mice to high levels of glyphosate during pregnancy and lactation, then assessed ASD-like behaviors in their offspring. Juvenile mice who were exposed to glyphosate in the womb and during lactation displayed ASD-like cognitive and social interaction deficits, unlike the unexposed group. Exposed offspring also had altered microbiomes compared with the unexposed group.

To understand the underlying mechanism, the researchers compared expression of sEH in the brains of exposed and unexposed offspring. Protein levels and gene expression of sEH were significantly higher in the brains of the exposed mice. Treatment with an sEH inhibitor from pregnancy through weaning prevented ASD-like behaviors in exposed offspring. According to the authors, these findings suggest that sEH inhibitors may prove promising in preventing or treating ASD.

Citation: Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wang D, Hwang SH, Hammock BD, Hashimoto K. 2020. Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase. Proc Natl Acad Sci U S A 117(21):11753–11759.

BPA exposure triggers epigenetic changes that alter metabolism

NIEHS grantees showed that early life exposure to bisphenol A (BPA) can trigger epigenetic changes that lead to metabolic dysfunction later in life. Epigenetic changes, which alter the way genetic information and proteins are expressed without directly changing DNA, represent an important and sensitive underlying mechanism by which metabolism can be reprogrammed by BPA during critical developmental periods.

The researchers exposed rats to BPA on postnatal days one, three, and five, and compared them with unexposed rats. Later, at 240 days old, the rats were split into groups that received either normal food or a high-fat diet. At one year of age, the rats were evaluated for changes in epigenetics and protein expression in the liver, an organ that plays an important role in metabolism.

Male rats exposed to BPA had epigenetic changes characteristic of older livers, which suggested premature epigenetic aging. Compared with controls, the exposed rats also had increased triglycerides and cholesterol, along with changes in gene expression related to cholesterol and fatty acid metabolism.

According to the authors, early life is a sensitive period for epigenetic modifications related to metabolism. Such changes can persist long after the initial exposure. Some of these changes may remain silent until triggered by a later life event, such as a high-fat diet, to drive metabolic dysfunction.

Citation: Trevino LS, Dong J, Kaushal A, Katz TA, Jangid RK, Robertson MJ, Grimm SL, Ambati CS, Putluri V, Cox AR, Kim KH, May TD, Gallo MR, Moore DD, Hartig SM, Foulds CE, Putluri N, Coarfa C, Walker CL. 2020. Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood. Nat Commun 11(1):2316..

TOP1 is critical for protecting neurons from neurodegeneration

Loss of the enzyme topoisomerase 1 (TOP1) leads to DNA damage in neurons and neurodegeneration, according to a new NIEHS-funded study. TOP1 plays an important role in facilitating the expression of long genes that are important for neuronal function. According to the research team, these data indicate that TOP1 maintains proper gene function in the central nervous system.

To evaluate the role of TOP1 in neurodegeneration, the researchers deleted TOP1 in mouse neurons and examined behavior, development, and underlying indicators of neurodegeneration, such as inflammation. Although the neurons developed normally, mice lacking TOP1 showed motor deficits and died prematurely. Those mice also showed signs of early neurodegeneration, with brains 3.5-times smaller at postnatal day 15 compared with controls. The researchers identified extensive inflammation in the brains of mice lacking TOP1, along with DNA damage and decreased expression of 132 long genes that are critical for normal neurodevelopment and function.

The team reported that mice lacking TOP1 had lower levels of nicotinamide adenine dinucleotide (NAD-plus), a compound critical in energy metabolism. When mice without TOP1 received supplemental NAD-plus, they lived 30% longer, had less inflammation, and showed improved neuronal survival. Neurodegeneration was partially improved, yet the mice still had motor deficits. This result indicated that when TOP1 was compromised, reducing neuronal loss was not sufficient to limit behavioral decline.

Citation: Fragola G, Mabb AM, Taylor-Blake B, Niehaus JK, Chronister WD, Mao H, Simon JM, Yuan H, Li Z, McConnell MJ, Zylka MJ. 2020. Deletion of topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration. Nat Commun 11(1):1962.