Chronic Toxoplasma gondii Infection Potentiates Parkinson’s Disease Course in Mice Model
Background: Toxoplasma gondii is a neuroinvasive protozoa pathogen that could manipulate its intermediate host's behavior. However, the possible link between T. gondii infection and the development of neurodegenerative disorders such as Parkinson’s disease (PD) has been proposed, we tested the hypothesis that in chronic toxoplasmosis neuroinflammation, and molecular mediators potentiate behavioral-cognitive impairments in BALB/c mice with PD.
Methods: To establish chronic toxoplasmosis by Tehran strain, cysts of T. gondii were injected intraperitoneally into BALB/c mice in Kerman, Iran in 2019. To induce the PD model, mice (BALB/c) were treated with Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The behavioral experiments such as anxiety and motor coordination were performed using the Open field and Rotarod tests. Additionally, we investigated the contribution of Toxoplasma-induced neuroinflammation, and behavioral-cognitive impairments in the PD mice model.
Results: Chronic toxoplasmosis caused PD-like symptoms and induced various behavioral changes in infected BALB/c mice. In T. gondii infected+MPTP treated group, T. gondii infection could potentiate PD in infected mice receiving MPTP and caused remarkable dysfunction in motor coordination and change in anxiety and depression-like behaviors similar or more severe than PD group.
Conclusion: Chronic T. gondii infection exacerbates pathological progression of PD in BALB/c mice brain by promoting neuroinflammation, and behavioral changes establishing.
2. Kirk MD, Pires SM, Black RE, et al. World Health Organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis. PLoS Med. 2015;12(12):e1001921.
3. Shojaee S, Firouzeh N, Keshavarz H, et al. Nanosilver Colloid inhibits Toxoplasma gondii tachyzoites and bradyzoites in vitro. Iran J Parasitol. 2019; 14(3): 362–367.
4. Charvat RA, Arrizabalaga G. Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function. Sci Rep. 2016; 6: 22997.
5. Dupont CD, Christian DA, Hunter CA. Immune response and immunopathology during toxoplasmosis. In: Seminars in Immunopathology. 2012; 34(6): 793–813.
6. Tyebji S, Seizova S, Garnham AL, et al . Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice. Brain Behav Immun. 2019;80:88–108.
7. Vonlaufen N, Kanzok SM, Wek RC, et al. Stress response pathways in protozoan parasites. Cell Microbiol. 2008;10(12):2387–99.
8. Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39(6):889–909.
9. Ramezani M, Shojaii M, Asadollahi M, et al. Seroprevalence of Toxoplasma gondii in Iranian patients with idiopathic Parkinson’s disease. Clin Exp Neuroimmunol. 2016;7(4):361–365.
10. Miman O, Kusbeci OY, Aktepe OC, et al. The probable relation between Toxoplasma gondii and Parkinson’s disease. Neurosci Lett. 2010;475(3):129–31.
11. Alvarado-Esquivel C, Méndez-Hernández EM, Salas-Pacheco JM, et al. Toxoplasma gondii exposure and Parkinson’s disease: a case–control study. BMJ Open. 2017; 7(2):e013019.
12. Fallahi S, Rostami A, Birjandi M, et al. Parkinson’s disease and Toxoplasma gondii infection: sero-molecular assess the possible link among patients. Acta Trop. 2017;173:97–101.
13. Mahmoudvand H, Sheibani V, Shojaee S, et al. Toxoplasma gondii infection potentiates cognitive impairments of Alzheimer’s disease in the BALB/c mice. J Parasitol. 2016;102(6):629–635.
14. Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc. 2007;2(1):141-51.
15. Gatkowska J, Wieczorek M, Dziadek B, et al. Behavioral changes in mice caused by Toxoplasma gondii invasion of brain. Parasitol Res. 2012;111(1):53–58.
16. Mohammadi F, Esfahlani MA, Shabani M. Erythropoietin ameliorates harmaline-induced essential tremor and cognition disturbances. Neurosci Lett. 2019;704:153–158.
17. Jung B-K, Pyo K-H, Shin KY, et al. Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer’s disease. PLoS One. 2012;7(3):e33312.
18. Tsai S, Chao C, Yin M. Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice. Eur J Pharmacol. 2011;670(2–3):441–7.
19. Afgar A, Fard-Esfahani P, Mehrtash A, et al. MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition. Cancer Biol Ther. 2016;17(11):1126–1138.
20. Fabiani S, Pinto B, Bonuccelli U, et al. Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases. J Neurol Sci. 2015;351(1–2):3–8.
21. Tyebji S, Seizova S, Hannan AJ, et al. Toxoplasmosis: A pathway to neuropsychiatric disorders. Neurosci Biobehav Rev. 2019;96:72–92.
22. Wang T, Sun X, Qin W, et al. From inflammatory reactions to neurotransmitter changes: implications for understanding the neurobehavioral changes in mice chronically infected with Toxoplasma gondii. Behav Brain Res. 2019;359:737–748.
23. Ihara F, Nishimura M, Muroi Y, et al. Toxoplasma gondii infection in mice impairs long-term fear memory consolidation through dysfunction of the cortex and amygdala. Infect Immun. 2016;84(10):2861–2870.
24. Fuks JM, Arrighi RBG, Weidner JM, et al. GABAergic signaling is linked to a hypermigratory phenotype in dendritic cells infected by Toxoplasma gondii. PLoS Pathog. 2012;8(12):e1003051.
25. Sedelis M, Hofele K, Auburger GW, et al. MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences. Behav Genet. 2000;30(3):171–82.
26. Alajmi RA, Al-Megrin WA, Metwally D, et al. Anti- Toxoplasma activity of silver nanoparticles green synthesized with Phoenix dactylifera and Ziziphus spina-christi extracts which inhibits inflammation through liver regulation of cytokines in Balb/c mice. Biosci Rep. 2019; 39(5):BSR20190379.
27. Mahmoud ME, Ui F, Salman D, et al. Mechanisms of interferon‐beta‐induced inhibition of Toxoplasma gondii growth in murine macrophages and embryonic fibroblasts: role of immunity‐related GTP ase M 1. Cell Microbiol. 2015;17(7):1069–83.
28. Heneka MT, O’Banion MK, Terwel D, et al. Neuroinflammatory processes in Alzheimer’s disease. J Neural Transm (Vienna). 2010;117(8):919–47.
29. Querfurth HW, LaFerla FM. Mechanisms of disease. N Engl J Med. 2010;362(4):329–44.
30. Rozenfeld C, Martinez R, Figueiredo RT, et al. Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration. Infect Immun. 2003;71(4):2047–57.
31. Rozenfeld C, Martinez R, Seabra S, et al. Toxoplasma gondii prevents neuron degeneration by interferon-γ-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-β1 production by infected microglia. Am J Pathol. 2005;167(4):1021–31.
32. Czarnewski P, Araújo ECB, Oliveira MC, et al. Recombinant TgHSP70 immunization protects against Toxoplasma gondii brain cyst formation by enhancing inducible nitric oxide expression. Front Cell Infect Microbiol. 2017;7:142.
33. Dincel GC, Atmaca HT. Nitric oxide production increases during Toxoplasma gondii encephalitis in mice. Exp Parasitol. 2015;156:104–12.
34. Singh S, Das T, Ravindran A, et al. Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson’s disease. Redox Rep. 2005;10(2):103–9.
35. Stibbs HH. Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Ann Trop Med Parasitol. 1985;79(2):153–7.
|Issue||Vol 16 No 4 (2021)|
|Methyl-4-phenyl-1 2 3 6-tetrahydropyridine (MPTP) Behavioral impairments; Inflammation Anxiety behaviors Parkinson Toxoplasma gondii|
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