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Journal of Neural Transmission

, Volume 126, Issue 2, pp 159–166 | Cite as

The role of exposure to pesticides in the etiology of Parkinson’s disease: a 18F-DOPA positron emission tomography study

  • Ruth DjaldettiEmail author
  • Adam Steinmetz
  • Amihai Rigbi
  • Christoph Scherfler
  • Werner Poewe
  • Yaniv Roditi
  • Lior Greenbaum
  • Mordechai Lorberboym
Neurology and Preclinical Neurological Studies - Original Article

Abstract

Susceptibility to Parkinson’s disease (PD) is believed to involve an interaction between genetic and environmental factors. The role of pesticides as a risk factor of PD and neurodegeneration remains controversial. An asymmetric decrease in ligand uptake on 18F-DOPA positron emission tomography (PET), especially in the dorsal putamen, is a sensitive marker of PD. The aim of this study was to examine the pattern of ligand uptake on 18F-DOPA PET in patients with PD exposed or not exposed to pesticides. The main sample included 26 Israeli patients with PD, 13 who were exposed to pesticides and 13 who were not, matched for age and disease duration. All underwent 18F-DOPA PET imaging, and an asymmetry index of ligand uptake between the ipsilateral and contralateral caudate, putamen, and whole striatum was calculated. No significant between-group differences were found in demographic variables, clinical asymmetry index (P = 0.15), or asymmetry index of ligand uptake in the putamen (P = 0.84), caudate (P = 0.78) and striatum (P = 0.45). Comparison of the 18F-DOPA results of the Israeli cohort with those of 17 non-pesticide-exposed patients with PD from Austria yielded no significant differences, further validating our findings. Our observations suggest that although exposure to pesticides might be a risk factor for PD, it does not have an effect on the asymmetry pattern in the nigrostriatal system over non-exposure. We assume that once the disease process is initiated in pesticide-exposed patients, the pathogenic mechanism does not differ from that of idiopathic PD.

Keywords

Pesticides Parkinson's disease Asymmetry index 18F-DOPA PET 

Abbreviations

CT

Computed tomography 

18F-DOPA

 L-6-[18F] fluoro-3,4-dihydroxyphenylalanine

MRI

Magnetic resonance imaging

PD

Parkinson’s disease

PET

Positron emission tomography

UPDRS

Unified PD Rating Scale

Notes

Author contributions

RD study design, interpretation of data and drafted the manuscript. AS study design, technical equipment and data acquisition. AR statistical analysis and drafted the manuscript. CS data acquisition. WP data acquisition. YR technical assistance and revision of manuscript. LG study design and drafted the manuscript. ML data acquisition and drafted the manuscript. All authors approved the final article.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

This study has been approved by our Institution’s Ethics Committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

References

  1. Arena JE, Stoessl AJ (2016) Optimizing diagnosis in Parkinson’s disease: radionuclide imaging. Parkinsonism Relat Disord 22(Suppl 1):S47–S51CrossRefGoogle Scholar
  2. Ascherio A, Chen H, Weisskopf MG, O’Reilly E, McCullough ML, Calle EE, Schwarzschild MA, Thun MJ (2006) Pesticide exposure and risk for Parkinson’s disease. Ann Neurol 60:197–203CrossRefGoogle Scholar
  3. Brigo F, Matinella A, Erro R, Tinazzi M (2014) [¹²³I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson’s disease and vascular or drug-induced parkinsonisms: a meta-analysis. Eur J Neurol 21:1369–1390CrossRefGoogle Scholar
  4. Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B (2000) Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 169:919–926CrossRefGoogle Scholar
  5. Dardiotis E, Xiromerisiou G, Hadjichristodoulou C, Tsatsakis AM, Wilks MF, Hadjigeorgiou GM (2013) The interplay between environmental and genetic factors in Parkinson’s disease susceptibility: the evidence for pesticides. Toxicology 307:17–23CrossRefGoogle Scholar
  6. Djaldetti R, Ziv I, Melamed E (2006) The mystery of motor asymmetry in Parkinson’s disease. Lancet Neurol 5:796–802CrossRefGoogle Scholar
  7. Du G, Lewis MM, Sterling NW, Kong L, Chen H, Mailman RB, Huang X (2014) Microstructural changes in the substantia nigra of asymptomatic agricultural workers. Neurotoxicol Teratol 41:60–66CrossRefGoogle Scholar
  8. Elbaz A, Moisan F (2016) The scientific bases to consider Parkinson’s disease an occupational disease in agriculture professionals exposed to pesticides in France. J Epidemiol Community Health 70:319–321CrossRefGoogle Scholar
  9. Elbaz A, Clavel J, Rathouz PJ, Moisan F, Galanaud JP, Delemotte B, Alpérovitch A, Tzourio C (2009) Professional exposure to pesticides and Parkinson disease. Ann Neurol 66:494–504CrossRefGoogle Scholar
  10. Firestone JA, Smith-Weller T, Franklin G, Swanson P, Longstreth WT Jr, Checkoway H (2005) Pesticides and risk of Parkinson disease: a population-based case-control study. Arch Neurol 62:91–95CrossRefGoogle Scholar
  11. Fitzmaurice AG, Rhodes SL, Cockburn M, Ritz B, Bronstein JM (2014) Aldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease. Neurology 82:419–426CrossRefGoogle Scholar
  12. Frigerio R, Sanft KR, Grossardt BR, Peterson BJ, Elbaz A, Bower JH, Ahlskog JE, de Andrade M, Maraganore DM, Rocca WA (2006) Chemical exposures and Parkinson’s disease: a population-based case-control study. Mov Disord 21:1688–1692CrossRefGoogle Scholar
  13. Gao HM, Hong JS (2011) Gene-environment interactions: key to unraveling the mystery of Parkinson’s disease. Prog Neurobiol 94:1–19CrossRefGoogle Scholar
  14. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefGoogle Scholar
  15. Kieburtz K, Wunderle KB (2013) Parkinson’s disease: evidence for environmental risk factors. Mov Disord 28:8–13CrossRefGoogle Scholar
  16. Liu R, Guo X, Park Y, Huang X, Sinha R, Freedman ND, Hollenbeck AR, Blair A, Chen H (2012) Caffeine intake, smoking, and risk of Parkinson disease in men and women. Am J Epidemiol 175:1200–1207CrossRefGoogle Scholar
  17. Lorberboym M, Treves TA, Melamed E, Lampl Y, Hellmann M, Djaldetti R (2006) [123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson’s disease. Mov Disord 21:510–514CrossRefGoogle Scholar
  18. McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA (2002) Environmental risk factors and Parkinson’s disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10:119–127CrossRefGoogle Scholar
  19. Moisan F, Spinosi J, Delabre L, Gourlet V, Mazurie JL, Bénatru I, Goldberg M, Weisskopf MG, Imbernon E, Tzourio C, Elbaz A (2015) Association of Parkinson’s disease and its subtypes with agricultural pesticide exposures in men: a case-control study in France. Environ Health Perspect 123:1123–1129CrossRefGoogle Scholar
  20. Moretto A, Colosio C (2013) The role of pesticide exposure in the genesis of Parkinson’s disease: epidemiological studies and experimental data. Toxicology 307:24–34CrossRefGoogle Scholar
  21. Navarro-Yepes J, Anandhan A, Bradley E, Bohovych I, Yarabe B, de Jong A, Ovaa H, Zhou Y, Khalimonchuk O, Quintanilla-Vega B, Franco R (2016) Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways. Mol Neurobiol 53:5229–5251CrossRefGoogle Scholar
  22. Priyadarshi A, Khuder SA, Schaub EA, Shrivastava S (2000) A meta-analysis of Parkinson’s disease and exposure to pesticides. Neurotoxicology 21:435–440Google Scholar
  23. Ritz BR, Paul KC, Bronstein JM (2016) Of pesticides and men: a California story of genes and environment in Parkinson’s Disease. Curr Environ Health Rep 3:40–52CrossRefGoogle Scholar
  24. Scherfler C, Seppi K, Mair KJ, Donnemiller E, Virgolini I, Wenning GK, Poewe W (2012) Left hemispheric predominance of nigrostriatal dysfunction in Parkinson’s disease. Brain 135:3348–3354CrossRefGoogle Scholar
  25. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW (2011) Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 119:866–872CrossRefGoogle Scholar
  26. Tomer R, Goldstein RZ, Wang GJ, Wong C, Volkow ND (2008) Incentive motivation is associated with striatal dopamine asymmetry. Biol Psychiatry 77:98–101CrossRefGoogle Scholar
  27. Uversky VN, Li J, Fink AL (2001) Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson’s disease. FEBS Lett 500:105–108CrossRefGoogle Scholar
  28. Van Maele-Fabry G, Hoet P, Vilain F, Lison D (2012) Occupational exposure to pesticides and Parkinson’s disease: a systematic review and meta-analysis of cohort studies. Environ Int 46:30–43CrossRefGoogle Scholar
  29. van der Mark M, Brouwer M, Kromhout H, Nijssen P, Huss A, Vermeulen R (2012) Is pesticide use related to Parkinson disease? Some clues to heterogeneity in study results. Environ Health Perspect 120:340–347CrossRefGoogle Scholar
  30. Weisskopf MG, Knekt P, O’Reilly EJ, Lyytinen J, Reunanen A, Laden F, Altshul L, Ascherio A (2010) Persistent organochlorine pesticides in serum and risk of Parkinson disease. Neurology 74:1055–1056CrossRefGoogle Scholar
  31. Wu B, Song B, Tian S, Huo S, Cui C, Guo Y, Liu H (2012) Central nervous system damage due to acute paraquat poisoning: a neuroimaging study with 3.0 T MRI. Neurotoxicology 33:1330–1337CrossRefGoogle Scholar
  32. Zhang J, Fitsanakis VA, Gu G, Jing D, Ao M, Amarnath V, Montine TJ (2003) Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: a link through mitochondrial dysfunction. J Neurochem 84:336–346CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Ruth Djaldetti
    • 1
    • 8
    Email author
  • Adam Steinmetz
    • 2
    • 8
  • Amihai Rigbi
    • 3
  • Christoph Scherfler
    • 4
  • Werner Poewe
    • 4
  • Yaniv Roditi
    • 1
  • Lior Greenbaum
    • 5
    • 6
    • 8
  • Mordechai Lorberboym
    • 7
    • 8
  1. 1.Department of NeurologyRabin Medical Center – Beilinson HospitalPetach TiqvaIsrael
  2. 2.Department of Nuclear MedicineRabin Medical Center – Beilinson HospitalPetach TikvaIsrael
  3. 3.Faculty of Education and Research AuthorityBeit Berl CollegeKfar SabaIsrael
  4. 4.Department of NeurologyMedical University InnsbruckInnsbruckAustria
  5. 5.The Danek Gertner Institute of Human GeneticsSheba Medical CenterTel HashomerIsrael
  6. 6.The Joseph Sagol Neuroscience CenterSheba Medical CenterTel HashomerIsrael
  7. 7.Department of Nuclear MedicineYitzhak Shamir Medical CenterZerifinIsrael
  8. 8.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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