Health Effects of Moldy Buildings – Parkinson’s Disease

 

 

This page lists medical journal articles discussing the possible relationship between Parkinson’s disease and moldy buildings.

The Health Effects of Moldy Buildings page of the Paradigm Change site provides further information on this topic.

 

Zhao G, Yin G, Inamdar AA, Luo J, Zhang N, Yang I, Buckley B, Bennett JW. Volatile organic compounds emitted by filamentous fungi isolated from flooded homes after Hurricane Sandy show toxicity in a Drosophila bioassay. Indoor Air. 2017 May;27(3):518-528. PMID: 27748984

 When cultured in a shared atmosphere with growing cultures of molds isolated after Hurricane Sandy, larval toxicity ranged from 15 to 80%. VOCs from Aspergillus niger 129B were the most toxic yielding 80% mortality to Drosophila after 12 days. The VOCs from Trichoderma longibrachiatum 117, Mucor racemosus 138a, and Metarhizium anisopliae 124 were relatively non-toxigenic. A preliminary analysis of VOCs was conducted using solid-phase microextraction-gas chromatography-mass spectrometry from two of the most toxic, two of the least toxic, and two species of intermediate toxicity. The more toxic molds produced higher concentrations of 1-octen-3-ol, 3-octanone, 3-octanol, 2-octen-1-ol, and 2-nonanone; while the less toxic molds produced more 3-methyl-1-butanol and 2-methyl-1-propanol, or an overall lower amount of volatiles. Our data support the hypothesis that at certain concentrations, some VOCs emitted by indoor molds are toxigenic.

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Lee S, Hung R, Yin G, Klich MA, Grimm C, Bennett JW. Arabidopsis thaliana as Bioindicator of Fungal VOCs in Indoor Air. Mycobiology. 2016 Sep;44(3):162-170. PMID: 27790067

In this paper, we demonstrate the ability of Arabidopsis thaliana to detect different mixtures of volatile organic compounds (VOCs) emitted by the common indoor fungus, Aspergillus versicolor, and demonstrate the potential usage of the plant as a bioindicator to monitor fungal VOCs in indoor air.

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Bennett JW. Silver linings: a personal memoir about Hurricane Katrina and fungal volatiles. Front Microbiol. 2015 Mar 18;6:206. PMID: 25852666

Some Scandinavian experts had hypothesized that mold volatile organic compounds (VOCs) might be the fungal metabolites to blame for sick building syndrome. I endeavored to test the hypothesis that some volatile mold metabolites might be toxic. Both Arabidopsis thaliana and Drosophila melanogaster exhibit a range of toxic symptoms that vary with the species of fungus, the duration of exposure, and other experimental parameters. Moreover, low concentrations of chemical standards of individual fungal VOCs such as 1-octen-3-ol also exhibit varying toxicity and cause neurotoxicity in a Drosophila model. Collectively, these data suggest that fungal VOCs may contribute to some of the adverse health effects reported by people exposed to damp indoor environments and that biogenic gas phase molecules deserve increased attention by the research community.

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Inamdar AA, Bennett JW. Volatile organic compounds from fungi isolated after hurricane katrina induce developmental defects and apoptosis in a Drosophila melanogaster model. Environ Toxicol. 2015 May;30(5):614-20. PMID: 24307503

In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies.

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Bennett JW, Inamdar AA. Are Some Fungal Volatile Organic Compounds (VOCs) Mycotoxins? Toxins (Basel). 2015 Sep 22;7(9):3785-804. PMID: 26402705

This paper describes the pros and cons of categorizing toxigenic fungal VOCs as mycotoxins, uses genomic data to expand on the definition of mycotoxin, and summarizes some of the linguistic and other conventions that can create barriers to communication between the scientists who study VOCs and those who study toxins. We propose that “volatoxin” might be a useful term to describe biogenic volatile compounds with toxigenic properties.

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Hung R, Lee S, Bennett JW. Fungal volatile organic compounds and their role in ecosystems. Appl Microbiol Biotechnol. 2015 Apr;99(8):3395-405. PMID: 25773975

The goal of this mini review is to orchestrate data on fungal VOCs obtained from disparate disciplines as well as to draw attention to the ecological importance of fungal VOCs in signaling between different species.

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Yin G, Padhi S, Lee S, Hung R, Zhao G, Bennett JW. Effects of Three Volatile Oxylipins on Colony Development in Two Species of Fungi and on Drosophila Larval Metamorphosis. Curr Microbiol. 2015 Sep;71(3):347-56. PMID: 26126831

The aim of this study is to investigate the effects of three volatile oxylipins  (1-octen-3-ol, (E)-2-hexenal, and 1-hexanol) on colony development in two fungi and on Drosophila larval metamorphosis. Conidia of both A. niger and P. chrysogenum plated in the presence of low concentrations (50 ppm) of these three volatile organic compounds (VOCs) formed fewer colony-forming units (CFUs) and exhibited reduced radial growth of colonies as compared to controls. Low concentration of these three VOCs can significantly inhibit the formation of CFUs and the growth of fungi. (R)-(-)-1-octen-3-ol imposed the greatest impact on fungal morphology compared to (S)-(+)-1-octen-3-ol and the racemic form. The three volatile oxylipins could also delay the metamorphosis of Drosophila and impose toxic effects on its pupae and adult stages.

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Inamdar AA, Bennett JW. A common fungal volatile organic compound induces a nitric oxide mediated inflammatory response in Drosophila melanogaster. Sci Rep. 2014 Feb 10;4:3833. PMID: 24509902

Using a Drosophila model, we previously demonstrated truncated life span and neurotoxicity with exposure to 1-octen-3-ol, the volatile organic compound (VOC) responsible for much of the musty odor found in mold-contaminated indoor spaces. In this report, using biochemical and immunological assays, we show that exposure to 0.5 ppm 1-octen-3-ol induces a nitric oxide (NO) mediated inflammatory response in hemocytes, Drosophila innate immune cells. Moreover, exposed Drosophila brains show increased peroxynitrite expression.

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Inamdar AA, Zaman T, Morath SU, Pu DC, Bennett JW. Drosophila melanogaster as a model to characterize fungal volatile organic compounds. Environ Toxicol. 2014 May;29(7):829-36.

We have established a reductionist Drosophila melanogaster model to evaluate the toxicity of fungal VOCs. In this report, we assessed the toxicity of fungal VOCs emitted from living cultures of species in the genera, Trichoderma, Aspergillus, and Penicillium and observed a detrimental effect on larval survival. We then used chemical standards of selected fungal VOCs to assess their toxicity on larval and adult Drosophila. We compared the survival of adult flies exposed to these fungal VOCs with known industrial toxic chemicals (formaldehyde [37%], xylene, benzene, and toluene). Among the tested fungal VOC standards, the compounds with eight carbons (C8) caused greater truncation of fly lifespan than tested non-C8 fungal VOCs and industrial toxins.

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Inamdar AA, Masurekar P, Hossain M, Richardson JR, Bennett JW. Signaling pathways involved in 1-octen-3-ol-mediated neurotoxicity in Drosophila melanogaster: implication in Parkinson’s disease. Neurotox Res. 2014 Feb;25(2):183-91. PMID: 23959949

Previously, we have pioneered Drosophila melanogaster as a reductionist model to show that 1-octen-3-ol, a musty-smelling volatile compound emitted by fungi and other organisms, causes loss of dopaminergic neurons and Parkinson’s disease-like symptoms in flies. Using our in vivo Drosophila system, the modulatory roles of important signaling pathways investigated in the context of 1-octen-3-ol-induced dopamine neurotoxicity. We found that Akt and JNK both protect against loss of dopamine activity associated with 1-octen-3-ol exposure, indicating the pro-survival role of these signaling pathways. Further, 1-octen-3-ol exposure was associated with activation of caspase 3, a hallmark for apoptosis.

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Inamdar AA, Hossain MM, Bernstein AI, Miller GW, Richardson JR, Bennett JW. Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19561-6. PMID: 24218591

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.

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Inamdar AA, Moore JC, Cohen RI, Bennett JW. A model to evaluate the cytotoxicity of the fungal volatile organic compound 1-octen-3-ol in human embryonic stem cells. Mycopathologia. 2012 Jan;173(1):13-20. PMID: 21858547

This study was aimed to determine the cytotoxicity of 1-octen-3-ol (“mushroom alcohol”), a major fungal volatile organic compound (VOC) associated with mushroom and mold odors. Using an airborne exposure technique, human embryonic stem cells were exposed for 1 h to different concentrations (0-1,000 ppm) of racemic 1-octen-3-ol and its enantiomers, (R)-(-)-1-octen-3-ol and (S)-(+)-1-octen-3-ol. Human embryonic stem cells exposed to 1-octen-3-ol, and its enantiomers in the vapor phase showed more cytotoxicity than those exposed to toluene.

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Araki A, Kanazawa A, Kawai T, Eitaki Y, Morimoto K, Nakayama K, Shibata E, Tanaka M, Takigawa T, Yoshimura T, Chikara H, Saijo Y, Kishi R. The relationship between exposure to microbial volatile organic compound and allergy prevalene in single-family homes. Sci Total Environ. 2012 Apr 15;423:18-26. PMID: 22405561

Microbial volatile organic compounds (MVOCs) are a type of VOCs produced by microorganisms. In this study, our aim was to investigate the relationship between asthma and allergies and MVOC exposure in single-family homes. The subjects were 624 inhabitants of 182 detached houses in six regions of Japan. These results are consistent with previous studies that have associated higher levels of 1-octen-3-ol exposure with increased irritation of nasal and ocular mucosae. Although the indoor-air concentrations of 1-octen-3-ol found in this study were relatively low, we conclude that exposure to MVOC may be related to rhinitis and conjunctivitis.

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Inamdar AA, Masurekar P, Bennett JW. Neurotoxicity of fungal volatile organic compounds in Drosophila melanogaster. Toxicol Sci. 2010 Oct;117(2):418-26. PMID: 20643751

Our study was designed to provide a reductionist approach toward studying fungal VOC-mediated toxicity using the inexpensive model organism, Drosophila melanogaster, and pure chemical standards of several important fungal VOCs. Low concentrations of the following known fungal VOCs, 0.1% of 1-octen-3-ol and 0.5% of 2-octanone; 2,5 dimethylfuran; 3-octanol; and trans-2-octenal, caused locomotory defects and changes in green fluorescent protein (GFP)- and antigen-labeled dopaminergic neurons in adult D. melanogaster. Locomotory defects could be partially rescued with L-DOPA. Ingestion of the antioxidant, vitamin E, improved the survival span and delayed the VOC-mediated changes in dopaminergic neurons, indicating that the VOC-mediated toxicity was due, in part, to generation of reactive oxygen species.

 

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