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Exposure to high pollution levels during pregnancy may increase risk of having child with autism

June 18, 2013 By Leave a Comment

AutismWomen in the U.S. exposed to high levels of air pollution while pregnant were up to twice as likely to have a child with autism as women who lived in areas with low pollution, according to a new study from Harvard School of Public Health (HSPH). It is the first large national study to examine links between autism and air pollution across the U.S.

“Our findings raise concerns since, depending on the pollutant, 20% to 60% of the women in our study lived in areas where risk of autism was elevated,” said lead author Andrea Roberts, research associate in the HSPH Department of Social and Behavioral Sciences.

The study appeared online June 18, 2013 in Environmental Health Perspectives.

Exposure to diesel particulates, lead, manganese, mercury, methylene chloride and other pollutants are known to affect brain function and to affect the developing baby. Two previous studies found associations between exposure to air pollution during pregnancy and autism in children, but those studies looked at data in just three locations in the U.S.

The researchers examined data from Nurses’ Health Study II, a long-term study based at Brigham and Women’s Hospital involving 116,430 nurses that began in 1989. Among that group, the authors studied 325 women who had a child with autism and 22,000 women who had a child without the disorder. They looked at associations between autism and levels of pollutants at the time and place of birth. They used air pollution data from the U.S. Environmental Protection Agency to estimate women’s exposure to pollutants while pregnant. They also adjusted for the influence of factors such as income, education, and smoking during pregnancy.

The results showed that women who lived in the 20% of locations with the highest levels of diesel particulates or mercury in the air were twice as likely to have a child with autism as those who lived in the 20% of areas with the lowest levels.

Other types of air pollution—lead, manganese, methylene chloride, and combined metal exposure—were associated with higher autism risk as well. Women who lived in the 20% of locations with the highest levels of these pollutants were about 50% more likely to have a child with autism than those who lived in the 20% of areas with the lowest concentrations.

Most pollutants were associated with autism more strongly in boys than girls. However, since there were few girls with autism in the study, the authors said this finding should be examined further.

Senior author Marc Weisskopf, associate professor of environmental and occupational epidemiology at HSPH, said, “Our results suggest that new studies should begin the process of measuring metals and other pollutants in the blood of pregnant women or newborn children to provide stronger evidence that specific pollutants increase risk of autism. A better understanding of this can help to develop interventions to reduce pregnant women’s exposure to these pollutants.”

 

Reference

Roberts AL, Lyall K, Hart JE, Laden F, Just AC, Bobb JF, Koenen KC, Ascherio A, Weisskopf MG. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environmental Health Perspectives, online June 18, 2013.

 

Filed Under: Autism, Environmental Medicine, Lead, Manganese Tagged With: , , , , , , ,

Link Between Parkinson’s Disease And Manganese Poisoning

August 22, 2011 By Leave a Comment

The Yeast PARK9 protein (Ypk9) is localized to the vacuole membrane. Shown are yeast cells expressing Ypk9 fused to the green fluorescent protein.

A connection between genetic and environmental causes of Parkinson’s disease has been discovered by a research team led by Aaron D. Gitler, PhD, Assistant Professor in the Department of Cell and Developmental Biology at the University of Pennsylvania School of Medicine. Gitler and colleagues found in 2009 a genetic interaction between two Parkinson’s disease genes (alpha-synuclein and PARK9) and determined that the PARK9 protein can protect cells from manganese poisoning, which is an environmental risk factor for a Parkinson’s disease-like syndrome.

Manganism, or manganese poisoning, is prevalent in such occupations as mining, welding, and steel manufacturing. It is caused by exposure to excessive levels of the metal manganese, which attacks the central nervous system, producing motor and dementia symptoms that resemble Parkinson’s disease.

In Parkinson’s patients, the alpha-synuclein protein normally found in the brain misfolds, forming clumps. Yeast cells, the model system in which Gitler studies disease proteins, also form clumps and die when this protein is expressed at high levels. These are the same yeast cells that bakers and brewers use to make bread, beer, and wine.

As a postdoctoral fellow at the Whitehead Institute in Cambridge, Massachusetts, Gitler and colleagues started looking for genes that could prevent the cell death caused by mis-folded alpha-synuclein in yeast. Eventually they found a few genes to test in animal models and some were able to protect neurons from the toxic effects of alpha-synuclein. “One of the genes that we found was a previously uncharacterized yeast gene called YOR291W. No one knew what it did back in 2006,” he recalls.

Yeast PARK9 gene (YPK9) helps protect cells from manganese toxicity. Yeast cells missing the YPK9 gene (ypk9) grow normally under standard conditions (- Mn2+) but are much more sensitive to manganese (+ Mn2+) than wild-type (WT) cells.

In the meantime, researchers in Europe published studies about a family that had an early-onset form of a type of Parkinson’s disease caused by mutations in the PARK9 gene. “When I read about this study, I wondered what the closest yeast gene was to the human PARK9 gene and it turned out to be YOR291W,” explains Gitler. “It was one of the genes that could rescue alpha-synuclein toxicity from our yeast screen. That was the big Eureka! and completely unexpected. It suggested that Parkinson’s disease genes could interact with each other in previously unexpected ways.”

Because of its similarity to the human PARK9 gene, Gitler and colleagues renamed the yeast gene to YPK9 (which stands for Yeast PARK9). Researchers at Purdue University and The University of Alabama teamed up with Gitler and his colleagues to show that the PARK9 gene could also protect neurons from alpha-synuclein’s toxic effects.

Next, the team set out to find the function of YPK9. Study co-first author, postdoctoral fellow Alessandra Chesi, PhD, discovered that YPK9 encodes a metal transporter protein. “Its sequence looks like other proteins that we know transport metals,” says Chesi.

She deleted the YPK9 gene from yeast and the cells were fine. Then she exposed YPK9-deficient yeast cells to an excess of different metals — zinc, copper, manganese, iron, etc. — to determine which metal it might transport. Of all the metals Chesi tested, she found that in the presence of manganese, the YPK9-deficient yeast did not grow as well. They were hypersensitive to manganese.

“This was astonishing, because it was known for years that welders and miners that inhale manganese get a Parkinson’s-like disease called manganese poisoning,” says Chesi. “The specific neurons that are lost in the miners are from the globus pallidus, a brain motor center. The European parkinsonism patients with the PARK9 mutation also lose neurons in this region.”

Gitler then found that the protein made by YPK9, the yeast gene equivalent of PARK9, is localized to the vacuole membrane in the yeast cell. Vacuoles are inner cell components that wall off toxic substances for later disposal. “Our hypothesis is that the vacuole, a bag in the cell that captures toxins, is sitting there and taking in manganese and sequestering it for detoxification, keeping it away from other cell organelles,” explains Gitler. “But, having a mutation in the PARK9 gene causes problems for this process in yeast and possibly in humans”.

 

Related Articles

Guilarte TR. Manganese and Parkinson’s disease: a critical review and new findings. Environ Health Perspect 2010;118 (8): 1071-80.

Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, et al. Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat Genet.2009; 41 (3): 308-15.

Aschner M, Erikson KM, Herrero Hernández E, Tjalkens R. Manganese and its role in Parkinson’s disease: from transport to neuropathology. Neuromolecular Med 2009; 11 (4): 252-66.

 

Filed Under: Manganese, Parkinson's Disease Tagged With: ,

Manganese In Drinking Water: Study Suggests Adverse Effects On Children’s Intellectual Abilities

August 14, 2011 By Leave a Comment

A team of researchers recently completed a study showing that children exposed to high concentrations of manganese in drinking water performed worse on tests of intellectual functioning than children with lower exposures.

A team of researchers led by Maryse Bouchard, adjunct professor at the Center for Interdisciplinary Research in Biology, Health, Environment and Society (CINBIOSE) of the Université du Québec à Montréal and a researcher at Sainte-Justine University Hospital, and Donna Mergler, professor emerita in the Department of Biological Sciences and a member of CINBIOSE, recently completed a study showing that children exposed to high concentrations of manganese in drinking water performed worse on tests of intellectual functioning than children with lower exposures. Their results are published in the prestigious scientific journal Environmental Health Perspectives, in an article entitled “Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water”.

Manganese: toxic in the workplace but harmless in water?
The neurotoxic effects of manganese exposure in the workplace are well known. This metal is naturally occurring in soil and in certain conditions is present in groundwater. In several regions of Quebec and Canada and in other parts of the world, the groundwater contains naturally high levels of manganese. Does it pose a danger? What effect might it have on children’s health? This is the first study to focus on the potential risks of exposure to manganese in drinking water in North America.

The study, carried out by researchers at the Université du Québec à Montréal, the Université de Montréal and the École Polytechnique de Montréal, examined 362 Quebec children, between the ages of 6 and 13, living in homes supplied by with groundwater (individual or public wells). For each child, the researchers measured the concentration of manganese in tap water from their home, as well as iron, copper, lead, zinc, arsenic, magnesium and calcium. The amount of manganese from both tap water and food was estimated from a questionnaire. Finally, each child was assessed with a battery of tests assessing cognition, motor skills, and behaviour.

Lead author Maryse Bouchard explains, “We found significant deficits in the intelligence quotient (IQ) of children exposed to higher concentration of manganese in drinking water. Yet, manganese concentrations were well below current guidelines.” The average IQ of children whose tap water was in the upper 20% of manganese concentration was 6 points below children whose water contained little or no manganese. The analyses of the association between manganese in tap water and children’s IQ took into account various factors such as family income, maternal intelligence, maternal education, and the presence of other metals in the water. For co-author Donna Mergler, “This is a very marked effect; few environmental contaminants have shown such a strong correlation with intellectual ability.” The authors state that the amount of manganese present in food showed no relationship to the children’s IQ.

What next?
So what can be done about it? Some of the municipalities where the study was conducted have already installed a filtration system that removes manganese from the water. According to one of the other co-authors of the study, Benoit Barbeau, NSERC Industrial Chair in Drinking Water at the École Polytechnique de Montréal, “A viable alternative solution is home use of filtering pitchers that contain a mixture of resins and activated carbon. Such devices can reduce the concentration of manganese by 60% to100% depending on filter use and the characteristics of the water.”

In Quebec, where the study was conducted, manganese is not on the list of inorganic substances in the Ministry of Sustainable Development, Environment and Parks Regulation respecting the quality of drinking water. “Because of the common occurrence of this metal in drinking water and the observed effects at low concentrations, we believe that national and international guidelines for safe manganese in water should be revisited.” the authors conclude.

 

Reference

Bouchard MF, Sauvé S, Barbeau B, Legrand M, Brodeur M-È, Bouffard T, et al. 2010. Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water. Environ Health Perspect :-. doi:10.1289/ehp.1002321.

 

Filed Under: Manganese, Minerals, Trace Elements Tagged With: , ,