Extramural Papers of the Month
By Nancy Lamontagne
- Air pollution linked to cognitive decline
- Predicting sudden changes in pollution patterns
- Epigenetic interactions between flame retardant exposure and autism mutation
- Early BPA exposure and asthma development
Air pollution linked to cognitive decline
NIEHS grantees report that a faster decline in the cognitive function of older women is associated with long-term exposure to particulate matter (PM) air pollution at levels typical of many areas of the United States. This is one of the first studies to examine the role of PM in cognitive decline over time.
The researchers evaluated exposures to both coarse and fine PM in relation to cognitive decline in the Nurses’ Health Study Cognitive Cohort, which included more than 19,000 U.S. women 70 to 81. The investigators performed baseline and follow-up cognitive testing that examined general cognition, verbal memory, category fluency, working memory, and attention. They also used geographic information system (GIS)-based models to estimate exposures over several intervals, including the preceding month and the previous seven to 14 years.
The study showed that higher levels of long-term exposure to both coarse and fine PM are associated with significantly faster cognitive decline. The researchers estimate that a 10-microgram per cubic meter increase in long-term PM exposure was cognitively equivalent to aging by approximately two years. If the findings are confirmed in other studies, reducing air pollution could offer a way to lessen age-related cognitive decline and, because cognitive decline often precedes the development of dementia, a way to reduce the future population burden of dementia.
Citation: Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F. (http://www.ncbi.nlm.nih.gov/pubmed/22332151) 2012. Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med 172(3):219-227.
Predicting sudden changes in pollution patterns
An NIEHS grantee and her colleague have developed a technique for forecasting major short-term changes in how oil spills will move in the ocean. The method, which is also applicable to harmful algal blooms and volcanic ash clouds, offers a tool for minimizing the impact of environmental disasters.
Over the last decade, the researchers have developed mathematical methods to describe hidden patterns in the way that air and water move, known as Lagrangian coherent structures (LCSs). The new technique uses these mathematical methods to detect LCS cores, which unite incoming flow from opposite directions and eject the resulting mass of water or air. LCS cores emerge before a sudden shape change in the contamination pattern and, thus, allow the forecast of dramatic changes that were previously considered unpredictable.
As a demonstration, the researchers showed that the method could have forecast the tigertail and coastal spread instabilities that occurred in the Deepwater Horizon oil spill. They developed high-precision forecasts of the location and time of these major instabilities, by detecting two strong LCS cores four to six days before the instabilities were observed.
Citation: Olascoaga MJ, Haller G. (http://www.pnas.org/content/early/2012/03/05/1118574109.abstract) 2012. Forecasting sudden changes in environmental pollution patterns. Proc Natl Acad Sci U S A; doi: 10.1073/pnas.1118574109 [Online 12 March 2012].
Epigenetic interactions between flame retardant exposure and autism mutation
NIEHS grantees studying the effects of flame retardant exposure on a mouse model of autism susceptibility found that the offspring of exposed mice had an increased risk for neurodevelopmental deficits associated with reduced sociability and learning. The work provides insight into the epigenetic interface of gene-environment interactions that are involved in the social and cognitive behaviors associated with neurodevelopmental disorders.
The researchers examined the effects of the flame retardant BDE-47 on the offspring of mice genetically modified to have a Mecp2 gene mutation (Mecp2(308)). Mutations in the epigenetic factor methyl-CpG binding protein 2 (MECP2), cause Rett syndrome, an X-linked autism spectrum disorder.
The study results showed gene-environment interactions occurred in the female, but not the male, offspring of the mice with the Mecp2 mutation. BDE-47 exposure had a negative impact on pup survival and learning in adult females. Female mice receiving perinatal exposure to the flame retardant had significantly lower DNA methylation levels in the adult brain, and these methylation levels correlated with decreased social behavior. However, the Mecp2 mutation reversed a social novelty-learning defect brought on by BDE-47 exposure, in a way that corresponded to increased levels of the methyltransferase Dnmt3a gene, which is required for learning and memory in the mouse brain.
Citation: Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, Lasalle JM. (http://www.ncbi.nlm.nih.gov/pubmed/22343140) 2012. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2(308) mutation. Hum Mol Genet; doi:10.1093/hmg/dds046 [Online 15 February 2012].
Early BPA exposure and asthma development
An NIEHS-supported grantee and colleagues report that prenatal bisphenol A (BPA) exposure promotes the development of allergic asthma in a mouse model. They also provide evidence that one reason the mice are susceptible during the prenatal period might be because BPA-metabolizing enzymes have not yet developed.
The mice received BPA in their drinking water beginning at one week before pregnancy. To separate the effects from prenatal BPA exposure and early-postnatal exposure, the researchers transferred some pups after birth from their BPA-exposed mother to an unexposed mother or vice versa. Half of the pups were sensitized with an experimental allergen and then later challenged by inhalations of the allergen. The researchers found that the pups exposed to BPA prenatally only, or prenatally and through breast milk, developed asthma after the allergic challenge. Pups that received only postnatal exposure did not develop asthma.
To look for a possible mechanism for BPA’s enhancement of asthma development, the investigators assessed the expression of Ugt2b1, an enzyme that metabolizes BPA. They found that the enzyme was not detectable in mouse fetuses and newborn pups, but its levels increased by day five and approached adult levels by day 25. Whether this mechanism is at work in humans must still be studied.
Citation: Nakajima Y, Goldblum RM, Midoro-Horiuti T. (http://www.ncbi.nlm.nih.gov/pubmed/22353195) 2012. Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study. Environ Health 11:8.
(Nancy Lamontagne is a science writer with MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training, Superfund Research Program, and Worker Education and Training Program.)