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Extramural Papers of the Month

By Jerry Phelps
December 2008

Parkinson’s Disease Linked to Vitamin D Deficiency

Fifty–five percent of Parkinson’s disease (PD) patients are insufficient in vitamin D, according to new research findings from an NIEHS-supported study at the Emory University School of Medicine. The number of Parkinson’s patients with vitamin D deficiency was higher than either healthy elderly people in the control group or Alzheimer’s disease patients. This finding adds to the evidence that low vitamin D levels are associated with Parkinson’s disease.

Most Americans get sufficient amounts of vitamin D through exposure to sunlight or by dietary supplements. However, the body’s ability to produce vitamin D in response to sun exposure decreases with age making elderly people more at risk for vitamin D deficiency.

Currently it is unclear whether there is a cause and effect relationship between vitamin D and Parkinson’s. The connection could be partly related to the decreased mobility of Parkinson’s patients, which may result in less sun exposure, or there could be a direct link between vitamin D insufficiency and the onset or progression of the disease.

Previous studies have shown that the region of the brain, the subtantia nigra, which produces dopamine and is most affected by Parkinson’s disease, has high levels of vitamin D receptors — suggesting that vitamin D may be important for the normal function of these cells. Emory doctors are conducting additional research to investigate whether vitamin D insufficiency is a cause or a result of having Parkinson’s.

Citation: Evatt ML, Delong MR, Khazai N, Rosen A, Triche S, Tangpricha V. ( Exit NIEHS 2008. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol 65(10):1348-1352.

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Nanoparticles Kill Blood Vessel Cells in the Human Brain

A study funded in part by the Superfund Basic Research Program at NIEHS shows that nanoparticles of aluminum oxide can adversely affect and even kill specialized endothelial cells that line blood vessels in the human brain.

The researchers designed this study to determine the effects of nanoscale particles of aluminum oxide on the human blood-brain barrier. In cell culture systems, endothelial cells that line the interior of blood vessels in the brain were treated with nano-alumina, normal sized alumina particles, carbon nanoparticles or normal sized carbon particles. After exposure, the researchers assessed cell structure, cell death, mitochondrial effects and tight junction proteins. Laboratory rats were given intravenous doses of nano-alumina.

In 2005, aluminum oxide nanoparticles accounted for 20 percent of the world production of nanoparticles. The particles are used in a variety of applications in the ceramics, electrical, engineering, and biomedical fields. Increases in the production and expansion of the uses of these particles will inevitably lead to greater human exposure.

According to the researchers, the nanoscale alumina and carbon particles were much more toxic than their respective compounds of normal particle size. Nano-alumina significantly increase cellular oxidative stress and disrupted the expression of tight junction proteins. The whole animal experiments confirmed the protein alteration with a loss of critical proteins in the cerebral blood vessels.

Citation: Chen L, Yokel RA, Hennig B, Toborek M. ( Exit NIEHS 2008. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J Neuroimmune Pharmacol 3(4):286-295.

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Cytosine-DNA Methyltransferase Mediates Carcinogen-Induced Gene Promoter Methylation

NIEHS-supported researchers studying the basic cellular and molecular events that occur after exposure to carcinogens report differences in DNA repair capacity in bronchial epithelial cell lines after low-dose treatment with methylnitrosourea and benzo(a)pyrene-diolepoxide. They also found that levels of cytosine-DNA methyltransferase 1 (DNMT1) increased significantly during the carcinogen exposure and were linked to promoter-hypermethylation of several genes in each transformed cell line. These findings may have implications for preventing lung cancer in smokers.

When the researchers employed strategies to reduce the production of the DNMT1 protein, cell transformation and gene silencing were reversed. Reduced DNMT1 production prior to carcinogen exposure prevented transformation and gene methylation.

These studies and findings describe a mechanistic link between increased DNMT1, methylation of tumor suppressor genes and reduced DNA repair capacity that together appear to cause cancer-like changes in lung epithelial cells. The study also provides evidence for the use of demethylation strategies to prevent lung cancer in smokers.

Citation: Damiani LA, Yingling CM, Leng S, Romo PE, Nakamura J, Belinsky SA. ( Exit NIEHS 2008. Carcinogen-induced gene promoter hypermethylation is mediated by DNMT1 and causal for transformation of immortalized bronchial epithelial cells. Cancer Res 68(21):9005-9014.

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Gas Stove Emissions Worsen Asthma Symptoms

Johns Hopkins scientists supported by NIEHS report that high levels of nitrogen dioxide gas from cooking and heating stoves in indoor environments aggravate asthma symptoms in inner-city children — especially preschool-aged children. Nitrogen dioxide gas is most prevalent in industrial settings, but it is also found at high levels in many poor, inner-city homes that have unvented gas stoves.

The research team compared the nitrogen dioxide levels in the homes of 150 inner-city Baltimore children aged 2-6 to the frequency and intensity of coughing, wheezing, shortness of breath and chest tightness. Each 20-point increase in nitrogen dioxide levels led to 10 percent more days of coughing and 15 percent more days of limited speech due to wheezing. Eighty-three percent of the homes had gas cooking stoves and 72 percent were heated with natural gas. Forty-two percent of the households had annual incomes less than $25,000.

Asthma is the most common pediatric chronic disease affecting 6.2 million children in the United States alone. It is widely known that severe asthma is most prevalent in the inner-city environment. The authors conclude that physicians caring for children with asthma should ask about their home’s heating and cooking appliances and recommend using alternatives if possible — or at least encourage the parents to have the stoves properly vented.

Citation: Hansel NN, Breysse PN, McCormack MC, Matsui EC, Curtin-Brosnan J, Williams DL, Moore JL, Cuhran JL, Diette GB. ( Exit NIEHS 2008. A longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner-city children with asthma. Environ Health Perspect 116(10):1428-1432.

(Jerry Phelps is a program analyst in the Program Analysis Branch of the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)

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