Of hurricanes, fungus and Parkinson's disease
Scientists at Rutgers and Emory universities have discovered that an organic compound, often emitted by fungi, causes symptoms of Parkinson's disease in fruit flies and may be linked to Parkinson's and other neurodegenerative diseases in humans.
Arati Inamdar, a research scientist in Rutgers' School of Environmental and Biological Sciences, used fruit flies to establish the connection between the compound, 1-octen-3-ol, popularly known as mushroom alcohol, and the degeneration of two specific genes involved in transport of dopamine – the chemical released by nerve cells to send messages to other nerve cells in the brain.
Results were published in the journal Proceedings of the National Academy of Sciences PNAS, of the United States of America.
"Parkinson's has been linked to exposure to environmental toxins, but those toxins were man-made chemicals.
"In this paper, we show that biologic compounds have the potential to damage dopamine and cause Parkinson's symptoms."
Arati Inamdar, research scientist, Rutgers' School of Environmental and Biological Sciences
For co-author Joan Bennett, the research was more than academic. Bennett was teaching at Tulane University in New Orleans when Hurricane Katrina struck the Gulf Coast in 2005. Her house developed mold and fungus as a result.
"I knew something about 'sick building syndrome, because I am an expert in toxic fungi,'" Bennett remembered. "I didn't believe in it, because I didn't think it would be possible to breathe in enough mold spores to get sick."
But collecting mold and mildew samples in her own house, wearing a mask, gloves and protective gear, made her ill. "While I was doing the sampling, I felt horrible – headaches, dizziness, nausea. I had a conversion experience," said Bennett, now a professor of plant biology and pathology and associate vice president for the promotion of women in science, engineering and mathematics at Rutgers.
When she came to Rutgers, Bennett looked for some way to understand the connection between fungi and symptoms like those she had experienced. She needed a genetic model, and Inamdar convinced her to use fruit flies. Bennett received an initial grant from the university to pursue the work.
Inamdar, Bennett and their colleagues spent approximately one year researching various compounds, trying to understand exactly how they worked. "Everybody knew there was some connection between fungal exposure and some health problems, but nobody had really looked at the mechanism before," Inamdar said.
In 2010, they found 1-octen-3-ol. It's a volatile organic compound – a vaporous collection of molecules that evaporate from liquids or solids.
When we smell something, pleasant or not, we're smelling volatile organic compounds.
Bennett, for example, remembers that the odors in her flooded house "were just terrible."
"This compound was really, really toxic – more toxic than industrial chemicals like benzene," Inamdar said. Applying 1-octen-3-ol to fruit flies, the scientists discovered that it attacked two genes that deal with dopamine.
Joan Bennett, an expert in fungi, had more than an academic interest in the work. One of the genes transports dopamine; the other packages it. Mushroom alcohol disrupts both the packaging of the dopamine and its transport, thus degenerating the neurons and causing the Parkinson's-like symptoms.
"There have been recent epidemiological studies indicating that people exposed to moldy or water-damaged buildings have developed neuropsychological problems and movement disorders.
"There have also been studies indicating that Parkinson's disease is increasing in rural areas, where it's usually attributed to pesticide exposure. But rural environments also have a lot of exposure to molds and other fungi, and our work suggests that 1-octen-3-ol might also be connected to the disease, particularly for people with a genetic susceptibility to it.
"We've given the epidemiologists some new avenues to explore."
Arati Inamdar, Rutgers' School of Environmental and Biological Sciences
Poor air quality from fungal growth in water-damaged, moldy buildings/residences is correlated with a negative impact on human health. The volatile organic compound 1-octen-3-ol is commonly emitted by molds and is responsible for much of the distinctive moldy odor associated with fungal colonization. Using a Drosophila model, we demonstrate via genetic, biochemical, and immunological studies that 1-octen-3-ol causes dopamine neuron degeneration through disruption of dopamine handling. These data demonstrate that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism. Moreover, it provides possible insights into reported movement disorders associated with human exposure to fungi and their volatile organic compounds.
Parkinson disease (PD) is the most common movement disorder and, although the exact causes are unknown, recent epidemiological and experimental studies indicate that several environmental agents may be significant risk factors. To date, these suspected environmental risk factors have been man-made chemicals. In this report, we demonstrate via genetic, biochemical, and immunological studies that the common volatile fungal semiochemical 1-octen-3-ol reduces dopamine levels and causes dopamine neuron degeneration in Drosophila melanogaster. Overexpression of the vesicular monoamine transporter (VMAT) rescued the dopamine toxicity and neurodegeneration, whereas mutations decreasing VMAT and tyrosine hydroxylase exacerbated toxicity. Furthermore, 1-octen-3-ol also inhibited uptake of dopamine in human cell lines expressing the human plasma membrane dopamine transporter (DAT) and human VMAT ortholog, VMAT2. These data demonstrate that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism.
Bennett and Inamdar were joined by co-author Muhammad Hossein and Jason Richardson from Rutgers Robert Wood Johnson Medical School, and Alison Bernstein and Gary Miller of Emory University. Richardson, a toxicologist, suggested some of the experiments with the transporter gene, and arranged for Bernstein and Miller to confirm Inamdar's observations in human in vitro cells.
Original press release: http://news.rutgers.edu/news/symptoms-parkinsons-disease-linked-fungus/20131110#.UoKe06Xd5uY