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Extramural Papers of the Month

By Jerry Phelps
September 2007

Parkinson-like Degenerative Changes Linked to Reduced Dopamine Storage

Mice with a decreased ability to package and store dopamine undergo a degenerative process that mimics Parkinson's disease, report NIEHS-supported neuroscientists at Emory University and The Parkinson's Institute. Mice genetically altered to produce only five percent of the normal levels of a protein called vesicular monoamine transporter 2 (VMAT2) were used in the experiment. VMAT2 is responsible for packaging dopamine for future release by neurons.

Lack of the neurotransmitter dopamine is responsible for many of the symptoms related to Parkinson's disease, a progressive neurodegenerative disease that strikes Americans at the rate of about 20/100,000 per year. Estimates of the current number of Parkinson's cases in the U.S. vary between 300,000 and 750,000. Current treatments include administration of the dopamine precursor, L-dopa.

The mice, known as VMAT2 LO, were carefully bred so that they were only deficient in the VMAT2 gene. Previous research found that this mouse strain included a chromosomal deletion spanning the α-syncline gene locus. The mice used in the current study were screened to verify the presence of α-syncline. This study represents the first data on VMAT2 LO mice with normal α-syncline expression. The investigators will continue this line of research using these mice to test compounds that can possibly slow the course of the Parkinson symptoms.

Citation: Caudle WM, Richardson JR, Wang MZ, Taylor TN, Gullet TS, McCormack AL, Colebrook RE, Di Monte DA, Meson PC, Miller GW ( Exit NIEHS Website. 2007. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci 27(30):8138-8148.

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Sunlight in Youth - Protective for MS?

Members of the Southern California Environmental Health Sciences Center funded by NIEHS report in the July edition of the journal Neurology evidence from a study of 79 pairs of identical twins that exposure to sunlight through various activities at an early age may be protective against developing multiple sclerosis (MS).

The study assessed sun exposure of 79 pairs of identical twins in the US and Canada. One twin in each pair had been diagnosed with MS. Study participants were questioned about a variety of exposures including the amount of time spent tanning, going to the beach and playing outdoor sports during childhood. The researchers found that the twin with MS usually had been exposed to less sun overall as a child than the twin without the disease. However, the protective effect was only found in female twins. According to the researchers, the lack of a protective effect in males may be due to a relatively small number of male twins in their study.

This study adds to the growing body of evidence that sunlight acting directly through an unknown mechanism or indirectly through stimulation of vitamin D production plays a role in preventing the development of multiple sclerosis as an adult.

Citation: Islam T, Gauderman WJ, Cozen W, Mack TM ( Exit NIEHS Website. 2007. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 69(4):381-388.

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IL-6 and Gender Differences in Liver Cancer Rates

A study in mice carried out by NIEHS grantees at the University of California San Diego may shed light on why the most common form of liver cancer strikes men with three to five times the frequency as women. Hepatocellular carcinoma arises from a variety of causes including viral hepatitis infection, chronic alcoholism and exposure to aflatoxin or a combination of these factors.

The research team treated mice with the potent liver carcinogen diethyl nitrosamine. All of the male mice - but only 10-20 percent of the female mice - developed liver tumors. Further investigation showed that the male mice produced much more of the inflammatory protein interleukin-6 (IL6) than the females. When IL-6 was eliminated in the male mice, the liver cancer rate dropped by about 90 percent bringing it in line with the rate in the female mice. Treating the male mice with estrogen also lowered IL-6 production and reduced liver disease to the same level as the female mice.

The researchers postulate that similar mechanisms may be responsible for the different rates of liver cancer in men and women and suggest potential interventions for humans as well. This discovery may have implications for bladder cancer, which also occurs more frequently in men.

Citation: Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M ( Exit NIEHS Website. 2007. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317(5834):121-124.

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Poor Diet Affects Respiratory Health of Teenagers

New epidemiologic research on teenagers in North America shows that a diet poor in essential vitamins, minerals and other antioxidant compounds is linked to increased risk for developing respiratory conditions - especially among smokers. The results suggest that higher dietary intake of antioxidant and anti-inflammatory micronutrients, such as vitamins A, C, and E and omega-3 fatty acids, such as those found in fish and algae, is linked to lower reports of cough and respiratory infections and less-severe asthma symptoms.

Lung growth and development parallels growth in physical stature; therefore the study subjects in late adolescence were near their peak of lung function. Analysis of questionnaires showed that 33 percent of the study subjects' diets were below USDA recommendations. One-third of the teenagers were overweight, another contributing factor for asthma, 72 percent did not take multivitamins, and 25 percent smoked.

This study adds to the body of knowledge that a healthy diet high in antioxidants is important for proper lung growth and development to reduce the risk of asthma as well as improve the general health of teens. The researchers conclude that snacks of fresh fruit and a simple nutritious family meal would be easy ways to help teens consume the proper amounts of essential nutrient.

Citation: Burns JS, Dockery DW, Neas LM, Schwartz J, Coull BA, Raizenne M, Speizer FE ( Exit NIEHS Website. 2007. Low dietary nutrient intakes and respiratory health in adolescents. Chest 132(1):238-245.

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