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The expression change of glial fibrillary acidic protein and tyrosine hydroxylase in substantia nigra of the Wistar rats exposed to chlorpyrifos: a novel environmental risk factor for Parkinson’s disease

Experimental Brain Research volume 238, pages 2041–2051 (2020)Cite this article

Abstract

Chlorpyrifos (CPF) is one of the most abundant and widely used pesticides in the world. CPF has detrimental effects on brain tissue, so it is possible to generate some neurodegenerative diseases. The aim of this study was to evaluate the effect of CPF on inducing the Parkinson’s disease affecting on central nervous system. 6 to 8-week-old animals were categorized into three groups. The first group was normal control which the animals did not received any treatment, while in the second group, CPF were injected (CPF; 5 mg/kg BW for 30 days intraperitoneally) and the sham group as the third group received DMSO. At the end of the CPF treatment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the brain tissues of rats. Proportion of neurons was analyzed by crystal violet assays and tunnel assay to detect apoptotic cells. Finally, the expression of GFAP and TH was investigated in the brain of animals. The results witnessed an increase in MDA and a decrease in SOD (P < 0.05) after the CPF treating. Moreover, results indicated that the proportion of neurons decreased in the second group vs. normal and sham groups significantly (P < 0.001). Additionally, in substantia nigra, the expression of GFAP had a significant increase and the TH had a remarkable decrease in CPF injected group in comparison to two other groups (P < 0.001). Furthermore, the numbers of apoptosis cells reduced in substantia nigra (P < 0.001) after the 30-day period of CPF injections. These results demonstrated that repeated exposure to CPF can induce PD via apoptotic cell death, histopathological disruption. It also altered the expression of dopaminergic neuron and changes the levels of oxidant and antioxidant enzymes in substantia nigra region which triggers PD. Hence, the CPF can be introduced as a risk factor for PD.

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References

  • Ali SJ, Ellur G, Patel K, Sharan K (2019) Chlorpyrifos exposure induces parkinsonian symptoms and associated bone loss in adult Swiss Albino Mice. Neurotox Res 36(4):700–711

    CAS  PubMed  Google Scholar 

  • Allbutt HN, Henderson JM (2007) Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson’s disease. J Neurosci Methods 159(2):195–202

    PubMed  Google Scholar 

  • Ascherio A, Schwarzschild MA (2016) The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol 15(12):1257–1272

    PubMed  Google Scholar 

  • Bajracharya SR, Prasad PN, Ghimire R (2017) Management of organophosphorus poisoning. J Nepal Health Res Council

  • Binukumar B, Bal A, Kandimalla RJ, Gill KD (2010) Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes. Mol Brain 3(1):1–20

    Google Scholar 

  • Carr RL, Graves CA, Mangum LC, Nail CA, Ross MK (2014) Low level chlorpyrifos exposure increases anandamide accumulation in juvenile rat brain in the absence of brain cholinesterase inhibition. Neurotoxicology 43:82–89

    CAS  PubMed  Google Scholar 

  • Caudle WM, Richardson JR, Wang M, Miller GW (2005) Perinatal heptachlor exposure increases expression of presynaptic dopaminergic markers in mouse striatum. Neurotoxicology 26(4):721–728

    CAS  PubMed  PubMed Central  Google Scholar 

  • Caughlan A, Newhouse K, Namgung U, Xia Z (2004) Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases. Toxicol Sci 78(1):125–134

    CAS  PubMed  Google Scholar 

  • Chen C-J, Liao S-L (2002) Oxidative stress involves in astrocytic alterations induced by manganese. Exp Neurol 175(1):216–225

    CAS  PubMed  Google Scholar 

  • Chen X-P, Chen W-F, Wang D-W (2014) Prenatal organophosphates exposure alternates the cleavage plane orientation of apical neural progenitor in developing neocortex. PLoS One 9(4):e95343

    PubMed  PubMed Central  Google Scholar 

  • Chiu C-D, Yao N-W, Guo J-H, Shen C-C, Lee H-T, Chiu Y-P, Chang C (2017) Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage. Oncotarget 8(55):94850

    PubMed  PubMed Central  Google Scholar 

  • Chorfa A, Bétemps D, Morignat E, Lazizzera C, Hogeveen K, Andrieu T, Baron T (2013) Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines. Toxicol Sci 133(2):289–297

    CAS  PubMed  Google Scholar 

  • Clairembault T, Kamphuis W, Leclair-Visonneau L, Rolli-Derkinderen M, Coron E, Neunlist M, Derkinderen P (2014) Enteric GFAP expression and phosphorylation in Parkinson’s disease. J Neurochem 130(6):805–815

    CAS  PubMed  Google Scholar 

  • Curtis AC, Sattler B (2018) Organophosphate insecticide exposure: a clinical consideration of chlorpyrifos regulation. J Am Assoc Nurse Pract 30(5):299–304

    PubMed  Google Scholar 

  • Estevan C, Vilanova E, Sogorb MA (2013) Chlorpyrifos and its metabolites alter gene expression at non-cytotoxic concentrations in D3 mouse embryonic stem cells under in vitro differentiation: considerations for embryotoxic risk assessment. Toxicol Lett 217(1):14–22

    CAS  PubMed  Google Scholar 

  • Fan J, Dawson TM, Dawson VL (2017) Cell death mechanisms of neurodegeneration neurodegenerative diseases. Springer, Berlin, pp 403–425

    Google Scholar 

  • Henley BM, Cohen BN, Kim CH, Gold HD, Srinivasan R, McKinney S, Lester HA (2017) Reliable Identification of Living Dopaminergic Neurons in Midbrain Cultures Using RNA Sequencing and TH-promoter-driven eGFP Expression. JoVE J Vis Exp 120:e54981

    Google Scholar 

  • Jin X, Wang L, Liu S, Zhu L, Loprinzi PD, Fan X (2020) The impact of mind-body exercises on motor function, depressive symptoms, and quality of life in Parkinson’s disease: a systematic review and meta-analysis. Int J Environ Res Public Health 17(1):31

    Google Scholar 

  • Joza S, Camicioli R, Ba F (2020) Falls in Parkinson’s disease and Lewy body dementia falls and cognition in older persons. Springer, Berlin, pp 191–210

    Google Scholar 

  • Lindner MD, Cain CK, Plone MA, Frydel BR, Blaney TJ, Emerich DF, Hoane MR (1999) Incomplete nigrostriatal dopaminergic cell loss and partial reductions in striatal dopamine produce akinesia, rigidity, tremor and cognitive deficits in middle-aged rats. Behav Brain Res 102(1–2):1–16

    CAS  PubMed  Google Scholar 

  • Mahmoud SM, Moneim AEA, Qayed MM, El-Yamany NA (2019) Potential role of N-acetylcysteine on chlorpyrifos-induced neurotoxicity in rats. Environ Sci Pollut Res 26(20):20731–20741

    CAS  Google Scholar 

  • Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, Eskenazi B (2010) Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ Health Perspect 118(12):1768–1774

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mehta A, Verma RS, Srivastava N (2005) Chlorpyrifos-induced alterations in rat brain acetylcholinesterase, lipid peroxidation and ATPases

  • Miller G, Kirby M, Levey A, Bloomquist J (1999) Heptachlor alters expression and function of dopamine transporters. Neurotoxicology 20(4):631–637

    CAS  PubMed  Google Scholar 

  • Mulla SI, Ameen F, Talwar MP, Eqani SAMAS, Bharagava RN, Saxena G, Ninnekar HZ (2020) Organophosphate pesticides: impact on environment, toxicity, and their degradation bioremediation of industrial waste for environmental safety. Springer, Berlin, pp 265–290

    Google Scholar 

  • Nagatsu T, Nakashima A, Ichinose H, Kobayashi K (2019) Human tyrosine hydroxylase in Parkinson’s disease and in related disorders. J Neural Transm 126(4):397–409

    CAS  PubMed  Google Scholar 

  • Niedzielska E, Smaga I, Gawlik M, Moniczewski A, Stankowicz P, Pera J, Filip M (2016) Oxidative stress in neurodegenerative diseases. Mol Neurobiol 53(6):4094–4125

    CAS  PubMed  Google Scholar 

  • Pallotta M, Ronca R, Carotenuto R, Porreca I, Turano M, Ambrosino C, Capriglione T (2017) Specific effects of chronic dietary exposure to chlorpyrifos on brain gene expression—a mouse study. Int J Mol Sci 18(11):2467

    PubMed Central  Google Scholar 

  • Paul KC, Sinsheimer JS, Cockburn M, Bronstein JM, Bordelon Y, Ritz B (2018) NFE2L2, PPARGC1α, and pesticides and Parkinson’s disease risk and progression. Mech Ageing Dev 173:1–8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poh Loh K, Hong Huang S, De Silva R, Tan H, Benny K, Zhun Zhu Y (2006) Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res 3(4):327–337

    Google Scholar 

  • Rahmati-Ahmadabad S, Shirvani H, Ghanbari-Niaki A, Rostamkhani F (2018) The effects of high-intensity interval training on reverse cholesterol transport elements: a way of cardiovascular protection against atherosclerosis. Life Sci 209:377–382

    CAS  PubMed  Google Scholar 

  • Rana AQ, Ahmed US, Chaudry ZM, Vasan S (2015) Parkinson’s disease: a review of non-motor symptoms. Expert Rev Neurother 15(5):549–562

    CAS  PubMed  Google Scholar 

  • Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, Whyatt R (2011) Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect 119(8):1196–1201

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rauh VA, Perera FP, Horton MK, Whyatt RM, Bansal R, Hao X, Peterson BS (2012) Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci 109(20):7871–7876

    CAS  PubMed  Google Scholar 

  • Salimi F, Hanigan I, Jalaludin B, Guo Y, Rolfe M, Heyworth JS, Marks GB (2020) Associations between long-term exposure to ambient air pollution and Parkinson’s disease prevalence: a cross-sectional study. Neurochem Int 133:104615

    PubMed  Google Scholar 

  • Shirvani H, Aslani J, Mohammadi ZF, Arabzadeh E (2019) Short-term effect of low-, moderate-, and high-intensity exercise training on cerebral dopamine neurotrophic factor (CDNF) and oxidative stress biomarkers in brain male Wistar rats. Comp Clin Pathol 28(2):369–376

    CAS  Google Scholar 

  • Slotkin TA, Brown KK, Seidler FJ (2005) Developmental exposure of rats to chlorpyrifos elicits sex-selective hyperlipidemia and hyperinsulinemia in adulthood. Environ Health Perspect 113(10):1291–1294

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sogorb MA, Fuster E, del Río E, Estévez J, Vilanova E (2016) Effects of mipafox, paraoxon, chlorpyrifos and its metabolite chlorpyrifos-oxon on the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells. Chem Biol Interact 259:368–373

    CAS  PubMed  Google Scholar 

  • Wang A, Cockburn M, Ly TT, Bronstein JM, Ritz B (2014) The association between ambient exposure to organophosphates and Parkinson’s disease risk. Occup Environ Med 71(4):275–281

    PubMed  PubMed Central  Google Scholar 

  • Wirdefeldt K, Adami H-O, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 26(1):1

    Google Scholar 

  • Zhang J, Dai H, Deng Y, Tian J, Zhang C, Hu Z, Zhao L (2015) Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young adult rats. Toxicology 336:17–25

    CAS  PubMed  Google Scholar 

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Affiliations

  1. Islamic Azad University of Dezful, Dezful, Islamic Republic of Iran

    Abolfazl Sheikh

  2. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Islamic Republic of Iran

    Khadijeh Sheikh

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  1. Abolfazl Sheikh
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  2. Khadijeh Sheikh
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Correspondence to Khadijeh Sheikh.

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Sheikh, A., Sheikh, K. The expression change of glial fibrillary acidic protein and tyrosine hydroxylase in substantia nigra of the Wistar rats exposed to chlorpyrifos: a novel environmental risk factor for Parkinson’s disease. Exp Brain Res 238, 2041–2051 (2020). https://doi.org/10.1007/s00221-020-05868-x

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  • DOI: https://doi.org/10.1007/s00221-020-05868-x

Keywords

  • Substantia nigra
  • CPF
  • Parkinson’s disease
  • GFAP
  • TH