ORIGINAL RESEARCH

Paraquat-induced model of Parkinson’s disease and detection of phosphorylated α-synuclein in the enteric nervous system of rats

About authors

Research Center of Neurology, Moscow, Russia

Correspondence should be addressed: Alla V. Stavrovskaya
Per. Obukha 5, Moscow, 103064; ur.liam@vats_alla

About paper

Funding: this work supported by the Russian Science Foundation (Grant 19-15-00320).

Acknowledgement: the authors thank their colleagues, Olshansky AS and Yamshchikova NG (the Laboratory of Experimental Pathology of the Nervous System), for their valuable contribution.

Author contribution: Stavrovskaya AV planned the study, analyzed the literature, collected, analyzed and interpreted the obtained data, conducted behavioral tests, administered drugs to the animals, and prepared the draft of the manuscript; Voronkov DN analyzed the literature, analyzed and interpreted the obtained data, prepared brain slides, conducted the histopathologic examination, and prepared the draft of the manuscript; Kutukova KA analyzed the literature, analyzed the obtained data, prepared jejunum slides, carried out the histopathologic examination, and prepared the draft of the manuscript; Ivanov MV prepared jejunum slides and carried out the histopathologic examination; Gushchina AS collected data, administered drugs to the rats, carried out behavioral tests, and monitored the animals’ health as a vet; Illarioshkin SN supervised the study and prepared the draft of the manuscript.

Received: 2019-08-12 Accepted: 2019-08-26 Published online: 2019-09-14
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  1. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014; (29): 1583–90.
  2. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017; (3): 17013.
  3. Chaudhuri K Ray, Titova N, editors. Nonmotor Parkinson’s: The hidden face. International Review of Neurology. Vol. 133. Academic Press, 2017; 794 р.
  4. Illarioshkin SN. Sovremennye predstavleniya ob etiologii bolezni Parkinsona. Nevrologicheskiy zhurnal. 2015; (4): 4–13.
  5. Jellinger KA. Synuclein deposition and non-motor symptoms in Parkinson disease. J Neurol Sci. 2011; (310): 107–11.
  6. Manning-Bog A, Mccormack A, Li J, Uversky V, Fink A, Di Monte D. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem. 2002; (277): 1641–4.
  7. Moretto A, Colosio C. Biochemical and toxicological evidence of neurological effects of pesticides: the example of Parkinson’s disease. Neurotoxicology. 2011; (32): 383–91.
  8. Fernagut PO, Hutson CB, Fleming SM, Tetreaut NA, Salcedo J, Masliah E, et al. Behavioral and histopathological consequences of paraquat intoxication in mice: Effects of alpha-synuclein over-expression. Synapse. 2007; (61): 991–1001.
  9. Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA. Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem. 2010; (285): 13621–9.
  10. Fahimi MA. Shechab S, Nemmar A, Adem A, Dhanasekaran S, Hasan MY. Daily Subacute Paraquat Exposure Decreases Muscle Function and Substantia Nigra Dopamine Level Physiol Res. 2013; (62): 313–21.
  11. Tieu K. A Guide to Neurotoxic Animal Models of Parkinson’s Disease Cold Spring Harb Perspect Med. 2011; (1): a009316.
  12. Bus JS, Gibson JE. Paraquat: Model for Oxidant-Initiated Toxicity. Environ Health Perspect. 1984; (55): 37–46.
  13. Wills J, Credle J, Oaks AW, Duka V, Lee JH, Jones J, et al. Paraquat, but Not Maneb, Induces Synucleinopathy and Tauopathy in Striata of Mice through Inhibition of Proteasomal and Autophagic Pathways. PLoS ONE. 2012; 7(1): 1–12. DOI: 10.1371/journal. pone.0030745.
  14. McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, et al. Environmental risk factors and Parkinson’s disease: Selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis. 2002; 10: 119–27.
  15. Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O, et al. Carrier-mediated processes in blood — brain barrier penetration and neural uptake of paraquat. Brain Res. 2001; (906): 135–42.
  16. McCormack AL, Di Monte DA. Effects of L-dopa and other amino acids against paraquat-induced nigrostriatal degeneration. J Neurochem. 2003; (85): 82–6.
  17. Izumi Y, Ezumi M, Takada-Takatori Y, Akaike A, Kume T. Endogenous Dopamine Is Involved in the Herbicide Paraquat-Induced Dopaminergic Cell Death Toxicological Sciences. 2014; 139 (2): 466–78.
  18. Thiruchelvam M, Brockel BJ, Richfield EK, Baggs RB, Cory- Slechta DA. Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: Environmental risk factors for Parkinson’s disease? Brain Res. 2000; (873): 225–34.
  19. Ossowska K, Wardas J, Smialowska M, Kuter K, Lenda T, Wieronska JM, et al. A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: An animal model of pre-clinical stages of Parkinson’s disease? Eur J Neurosci. 2005; (22): 1294–304.
  20. Junboa Z, Yongtaob Y, Hongboa Li, Fenshuanga Z, Ruyuna L, Chun’aia Y. Experimental study of sucralfate intervention for paraquat poisoning in rats. Environmental Toxicology and Pharmacology. 2017; (53): 57–63.
  21. Riederer P, Jellinger KA, Kolber P, Hipp G, Sian-Hulsmann J, Kruger R. Lateralisation in Parkinson disease. Cell Tissue Res. 2018; (373): 297. https://doi.org/10.1007/s00441-018-2832-z.
  22. Djaldetti R, Ziv I, Melamed E. The mystery of motor asymmetry in Parkinson’s disease. The Lancet Neurology. 2006; 5 (9): 796–802. DOI: 10.1016/s1474-4422(06)70549-x.
  23. Li WD, Zhao YZ, Chou IN. Paraquat-induced cytoskeletal injury in cultured cells. Toxicol Appl Pharmacol. 1987; 91 (1): 96–106.
  24. Phillips RJ, Pairitz JC, Powley TL. Age-related neuronal loss in the submucosal plexus of the colon of Fischer 344 rats. Neurobiol Aging. 2007; 28 (7): 1124–37.
  25. Phillips RJ, Hudson CN, Powley TL. Sympathetic axonopathies and hyperinnervation in the small intestine smooth muscle of aged Fischer 344 rats. Auton Neurosci. 2013; 179 (1–2): 108–121. DOI: 10.1016/j.autneu.2013.09.002.
  26. Muntané G, Ferrer I, Martinez-Vicente M. α-Synuclein phosphorylation and truncation are normal events in the adult human brain. Neuroscience. 2012; (200): 106–19. DOI: 10.1016/j. neuroscience.2011.10.042.
  27. Toygar M, Aydin I, Agilli M, Aydin FN, Oztosun M, Gul H, et al. The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity. Hum Exp Toxicol. 2015; 34 (2): 198–204. DOI: 10.1177/0960327114533808.
  28. Resnikoff H, Metzger JM, Lopez M, Bondarenko V, Mejia A, Simmons HA, et al. Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates. J Inflamm Res. 2019; (12): 113–26. DOI: 10.2147/JIR.S196552.
  29. Zhang J, Li X, Li JD. The Roles of Post-translational Modifications on α-Synuclein in the Pathogenesis of Parkinson's Diseases. Front Neurosci. 2019; (13): 381. DOI: 10.3389/fnins.2019.00381.
  30. Yan F, Chen Y, Li M, Wang Y, Zhang W, Chen X, et al. Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease. Medicine (Baltimore). 2018; 97 (28): e11337. DOI:10.1097/ MD.0000000000011337.