Papers of the Month
By Sara Mishamandani
Effects of low arsenic levels during pregnancy and fetal growth
Consuming water and food with low levels of arsenic while pregnant may affect fetal growth, according to a new study by NIEHS grantees. The study is one of the first to report an association between low-level exposure to arsenic during pregnancy and birth outcomes.
Unlike the majority of epidemiological studies on arsenic exposure, this population-based, prospective study explored exposures at levels common in the U.S. Researchers analyzed 706 mother-infant pairs exposed through drinking water and diet. They measured urinary arsenic from each mother and compared it to the birth weight of her baby, adjusting for maternal prepregnancy weight.
Researchers found that decreased head circumference at birth was associated with higher levels of arsenic in the mother’s urine during her second trimester. They also found associations with changes to birth weight and length, with mixed effects based on the sex of the newborn and maternal weight status. For example, the association between higher arsenic exposure and shorter birth length was only observed in males. They also observed that arsenic exposure was related to lower birthweight in female babies born to overweight or obese mothers, but the association was not significant for males or females of healthy weight mothers.
Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect; doi: 10.1289/ehp.1510065 [Online 8 March 2016].
Anti-inflammatory chemical may offer new tool for depression treatment
An NIEHS grantee and colleagues discovered that a chemical inhibitor of the soluble epoxide hydrolase (sEH) enzyme may be a new tool to treat depression. The enzyme plays a key role in inflammation, which is involved in depression. Researchers found that the sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea (TPPU), displayed rapid antidepressant effects in mice.
Researchers observed mice for depression-like behavior after repeated social stress. They found that administering TPPU reduced depression-like behaviors. Inhibiting sEH in the mice also produced resilience to the repeated stress.
The researchers also observed higher levels of sEH expression in key brain regions of the chronically stressed mice than in mice not subject to repeated stress. They then examined postmortem human brain samples from patients with psychiatric diseases, including depression, and found that these brains expressed higher levels of sEH than brain samples from people with no psychiatric diagnoses.
Depression, the most common and debilitating psychiatric disorder, affects 350 million people around the world. This study improves the understanding of mechanisms involved in depression by showing that sEH is involved in its development. As a result, sEH inhibitors have potential as effective therapeutic drugs for depression.
Ren Q, Ma M, Ishima T, Morisseau C, Yang J, Wagner KM, Zhang JC, Yang C, Yao W, Dong C, Han M, Hammock BD, Hashimoto K. 2016. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A 113(13):E1944-E1952. (Story)
Effects of low-level lead exposure on learning and memory
In an NIEHS-funded study, researchers found that exposure to lead affected associative learning and memory in rats. The researchers also observed differences in males and females, and varied effects from exposure during different developmental windows, suggesting a complex interaction between sex, developmental windows of exposure, and effects on memory.
The researchers exposed both male and female rats to three environmentally relevant levels of lead during three developmental periods. They categorized overlapping developmental periods as perinatal, or gestation to postnatal day 21; early postnatal, or postnatal days 1-21; and late postnatal, or postnatal days 1-55. They then used a test that required coordination of the medial prefrontal cortex and hippocampal brain regions to assess the effects of lead on learning and memory.
In female rats, researchers saw significantly impaired memory recall with early and late postnatal exposure to lead but not with perinatal exposure. In contrast, male rats only had significant recall deficits with exposure during the perinatal period.
This work highlights the complex interactions between lead exposure and other factors on development. In addition to adversely affecting the formation and recall of memories, damage to the prefrontal cortex and hippocampus may also underlie emotional and behavioral dysregulation frequently seen in children exposed to lead.
Anderson DW, Mettil W, Schneider JS. 2016. Effects of low level lead exposure on associative learning and memory in the rat: influences of sex and developmental timing of exposure. Toxicol Lett 246:57-64.
Air pollution linked to microRNA changes
Short-term exposure to elemental carbon in air pollution is associated with expression of human and viral microRNAs that may influence immune response and other biological pathways, according to an NIEHS-funded study. MicroRNAs are small non-coding RNA molecules that can suppress expression of certain genes in the body and likely play a role in susceptibility to environmental chemicals.
Researchers examined microRNA profiles for participants in the Beijing Truck Driver Air Pollution Study, which included 60 truck drivers and 60 office workers who were highly exposed to air pollution for a short time. Truck drivers were directly exposed to traffic emissions, particularly from diesel exhausts and road dusts. The office workers represented the highly exposed urban residential population of Beijing, which have a higher exposure to secondary oxidized traffic particles. The researchers obtained data on each participant’s personal exposure to particulate matter and elemental carbon using a personal monitor, and collected daily ambient particulate data from monitoring stations around the city.
Expression of microRNAs was not significantly associated with personal particulate matter exposure. However, short-term elemental carbon exposure was associated with altered expression of 46 human and seven viral microRNAs. The viral microRNAs associated with elemental carbon levels, which differed between office workers and truck drivers, suggest possible mechanisms through which viral miRNAs may worsen the health effects of air pollution.
Hou L, Barupal J, Zhang W, Zheng Y, Liu L, Zhang X, Dou C, McCracken JP, Diaz A, Motta V, Sanchez-Guerra M, Wolf KR, Bertazzi PA, Schwartz JD, Wang S, Baccarelli AA. 2016. Particulate air pollution exposure and expression of viral and human microRNAs in blood: the Beijing Truck Driver Air Pollution Study. Environ Health Perspect 124(3):344-350.