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Environmental Factor, July 2012

Extramural papers of the month

By Nancy Lamontagne

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Gene variants linked with faster Parkinson’s disease progression

NIEHS grantees report that Parkinson's disease patients with two specific variants of the alpha-synuclein (SNCA) gene progressed toward motor decline significantly faster than patients without these variants. This work could lead to new therapies and help identify those who would benefit most from early intervention.

The researchers followed 233 well-characterized Parkinson’s disease patients in central California for an average of 5.1 years, and found that carriers of the Rep1 263bp variant of the SNCA gene had a four-fold higher risk of faster motor decline. Patients with both the Rep1 263bp promoter and rs356165 variants had an even stronger trend in progression toward motor decline.

Although the findings need replication in other well-characterized Parkinson’s disease populations, the researchers say that their work shows that these gene variants could be used to identify patients who will likely experience faster disease progression. The work also points to the alpha-synuclein pathway as a promising potential therapeutic target.

CitationRitz B, Rhodes SL, Bordelon Y, Bronstein J. (http://www.ncbi.nlm.nih.gov/pubmed/22615757)  2012. Alpha-synuclein genetic variants predict faster motor symptom progression in idiopathic Parkinson disease. PLoS One 7(5):e36199.

Cardiovascular effects of Beijing Olympics air pollution reduction

The Chinese government shut down factories and limited automobile traffic during the Beijing Olympics, to lessen air pollution. These temporary changes in air pollution levels were associated with acute changes in cardiovascular biomarkers in healthy young people, according to a new study from NIEHS grantees. The research adds evidence that higher levels of air pollution are linked with an increased risk of cardiovascular problems.

The researchers recruited 125 male and female resident doctors, who worked at a central Beijing hospital, to participate in the study. Participants had never smoked, were free of disease, and had an average age of 24. They visited the clinic before the air pollution controls were in place, while the pollution controls were used, and after the games had ended.

During the Olympics, the study participants showed significant reductions in von Willebrand factor and soluble CD62P levels, which are both associated with blood coagulation. Soluble CD62P and systolic blood pressure levels increased significantly once the pollution controls were lifted after the Olympics.

CitationRich DQ, Kipen HM, Huang W, Wang G, Wang Y, Zhu P, Ohman-Strickland P, Hu M, Philipp C, Diehl SR, Lu SE, Tong J, Gong J, Thomas D, Zhu T, Zhang JJ. (http://www.ncbi.nlm.nih.gov/pubmed/22665106)  2012. Association between changes in air pollution levels during the Beijing Olympics and biomarkers of inflammation and thrombosis in healthy young adults. JAMA 307(19):2068-2078.

Environmental exposures influence behavior of later generations

A new NIEHS-funded study shows that animals whose ancestors were exposed to a fungicide have a more profound reaction to stress than the offspring of unexposed animals. The work demonstrates that an ancestor’s exposure can influence the stress response of future generations.

The authors of the study used a systems biology approach by examining genetic and molecular changes in the brain as well as behavior. They exposed gestating female rats to the fungicide vinclozolin and later performed testing on the third generation of offspring. The third generation offspring from the exposed rats showed differences in physiology and metabolic activity compared to descendants of unexposed rats. When exposed to stress during adolescence, the offspring of exposed rats had greater anxiety, sensitivity to stress, and more activity in stress-related regions of the brain.

CitationCrews D, Gillette R, Scarpino SV, Manikkam M, Savenkova MI, Skinner MK. (http://www.ncbi.nlm.nih.gov/pubmed/22615374)  2012. Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci U S A 109(23):9143-9148.

Semiconducting properties of nanoparticles linked with oxidative damage

An NIEHS grantee and his colleagues used the semiconducting properties of metal oxide nanoparticles to quickly identify nanoparticles that could cause toxicity in vitro and in vivo. This new method could speed assessment of emerging new nanomaterials and prioritize materials for further study.

The researchers first predicted which of 24 metal oxide nanoparticles might cause cell injury, based on semiconducting properties, and then analyzed all the nanoparticles with a high-throughput assay that assessed oxidative damage to a variety of cell types. In only a few hours, the screen identified oxidative damage from six nanoparticles — the same ones that previously met the researchers' predictive criteria. Animal tests of the 24 metal oxide nanoparticles showed that the same six caused lung inflammation.

CitationZhang H, Ji Z, Xia T, Meng H, Low-Kam C, Liu R, Pokhrel S, Lin S, Wang X, Liao YP, Wang M, Li L, Rallo R, Damoiseaux R, Telesca D, Madler L, Cohen Y, Zink JI, Nel AE. (http://www.ncbi.nlm.nih.gov/pubmed/22502734)  2012. Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation. ACS Nano 6(5):4349-4368.

(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.)



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