Scientific Journal Of King Faisal University
Basic and Applied Sciences

ع

Scientific Journal of King Faisal University / Basic and Applied Sciences

Lesions in the Hippocampus and Substantia Nigra of Wistar Rats’ Brains Induced by Organophosphate Insecticide

(Ebtihajah Abd Alrazaq Zaalan, Mahmoud Qassem and Muhammad Muayyad Bilal)

Abstract

As little is known about the neurotoxicity of the histological structure of the brain, this study focuses on the histological side of four- to six-month-old adult Wistar rat brains, which were examined after 0.1 mg\g organophosphate had been administered orally. In this study, the lesions were mainly localized at the hippocampus and substantia nigra (compacta pars) region. Distinct areas of necrotic and apoptotic tissues were detected in the CA1, CA2, and dentate gyrus of the hippocampus and compacta pars of the substantia nigra. Programmed cell death in the dentate gyrus was observed as early as 72 hours after treatment and necrosis of some brain regions. Moreover, Lewy bodies were noticed in the compacta pars of the substantia nigra. The most important symptoms of parkinsonism were observed in the substantia nigra (compacta pars). These were decreased neurons, increased neuronal melanin in the neurons, and increased glial cells. The degeneration of some neurons was reported in the polymorphic and pyramidal layers. The data showed an increase in the density of the axon membrane and several changes to the axis structure, such as the disappearance of the myelin sheath in some areas along the axis.

KEYWORDS
CA1, CA2, cell degeneration, compacta pars, dentate gyrus, Lewy bodies

PDF

References

Ahmed, D., Abdel-Rahman, R.H. and Salama, M. (2017). Malathion neurotoxic effects on dopaminergic system in mice: Role of inflammation. Journal Biomedical Science, 6(4), 1–30.
Anthony, J., Intorcia, J., Filon, R., Brittany, H., Geidy, E., Serrano, L.I. and Thomas, B.G. (2019). A Modification of the Bielschowsky Silver Stain for Alzheimer Neuritic Plaques: Suppression of Artifactual Staining by Pretreatment with Oxidizing Agents. Arizona, USA: Banner Sun Health Research Institute.
Astiz, M., Diz-Chaves, Y. and Garcia-Segura, L.M. (2013). Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lipopolysaccharide in the hippocampus and striatum of male mice. Toxicol, 272(2), 263–71.
Banks, C.N. and Lein, P.J. (2012). A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation. Neurotoxicology, 33(3), 575–84.
Binukumar, B.K., Bal, A. and Gill, K.D. (2011). Chronic dichlorvos exposure: Microglial activation, proinflammatory cytokines and damage to nigrostriatal dopaminergic system. NeuroMolecular Medicine, 13(4), 251–65.
Blaszczyk, J.W. (2018). Parkinson’s disease and neurodegeneration: GABA-collapse hypothesis. Frontiers in Neuroscience, 269(10), 1–8.
Carbaja, I.C., Laguna, A. and Giménez, J.R. (2019). Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis. Nature Communications, 973(10), 1–19.
Delle D.A., Klos, K.J. and Fujishiro, H. (2008). Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol, 65(8),1074–80.
Dennis, W., Dickson, M.D. (2018). Neuropathology of Parkinson disease. HHS Public Access, 46(11), 30–3.
Dirnberger, G. and Jahanshahi, M. (2013). Executive dysfunction in Parkinson’s disease. Journal of Neuropsychology, 7(2), 193–224.
Dorri, S.A., Hosseinzadeh, H., Abnous, K., Hasani, F.V. and Robati, R.Y. (2015). Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iran Journal Basic Medicine, 18(10), 958–66.
Dugger, B.N. and Dickson, D.W. (2016). Pathology of neurodegenerative diseases. Cold Spring Harbor Laboratory Press, 9(7), 1–22.
Farkhondeh, T., Mehrpour, O. and Buhrmann, C. (2020). Organophosphorus compounds and MAPK signaling pathways. International Journal of Molecular Sciences, 4258(21), 1–17.
García, A.M., Kun, A. and Calero, M. (2021). The neuromelanin paradox and its dual role in oxidative stress and neurodegeneration. Antioxidants, 124(10), 1–19.
Hernández, A.F., González, A.B., López, F.I. and Lacasaña, M. (2016). Systematic reviews on neurodevelopmental and neurodegenerative disorders linked to pesticide exposure: Methodological features and impact on risk assessment. Environ Int, 92-93(6), 657–79.
Jiang, Q., Zhang, L., Ding, G., Davoodi B.E., Li, Q., Li, L., Sadry, N., Nedergaard, M., Chopp, M. and Zhang, Z. (2017). Impairment of the glymphatic system after diabetes. Blood Flow Metab, 37(4), 1326–37.
Kamanyire, R. and Karalliedde, L. (2004). Organophosphate toxicity and occupational exposure. Occupational Medicine, 54(2), 69–75
Kouli, A., Camacho, M. and Allinson, K. (2020). Neuroinflammation and protein pathology in Parkinson’s disease dementia. Acta Neuropathol Commun, 211(8), 1–19.
Maiti, P., Manna, J. and Dunbar, G.L. (2017). Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments. Translational Neurodegeneration, 28(6), 1–35.
Martinez, L.G., Maccioni, R.B. and Andrade, V. (2019). Neuroinflammation as a common feature of neurodegenerative disorders. Neuroinflammation in Brain Disorders, 1008(10). 1–17.
Narayan, S., Liew, Z., Paul, K., Lee, P.C. and Sinsheimer, J.S. (2013). Household organophosphorus pesticide use and Parkinson’s disease. International Journal of Epidemiology, 42(5), 1476–85.
Nury, T., Lizard, G. and Vejux, A. (2020). Lipids nutrients in Parkinson and Alzheimer’s diseases: Cell death and cytoprotection. International Journal of Molecular Sciences, 2501(21), 1–19.
Pajares, M., Rojo, A.I. and Manda, G. (2020). Inflammation in Parkinson’s disease: Mechanisms and therapeutic implications. Cells, 1687(9), 1–32.
Pearson, J.N. and Pate, M. (2016). The role of oxidative stress in organophosphate and nerve agent toxicity. HHS Public Access, 1378(1), 17–24.
Saha, A.R., Ninkina, N.N., Hanger, D.P., Anderton, B.H. and Davies, A.M. (2000). Induction of neuronal death by alpha-synuclein. Europe Journal Neuroscience, 12(8), 3073–7.
Salyha, Y.T. (2013). Chlorpyrifos leads to oxidative stress-induced death of hippocampal cells in vitro. Neurophysiol, 45(3), 193–9.
Sánchez-Santed, F., Colomina, M.T. and Hernández, E.H. (2016). Organophosphate pesticide exposure and neurodegeneration. Cortex, 74, 417–26.
Selkoe, D.J. (1994). Alzheimer’s disease beyond the path to therapeutics. Neurobiol, 15(2), 131–3.
Vila, M.D. (2019). Neuromelanin, aging, and neuronal vulnerability in Parkinson’s disease. Movement Disorders, 34(10), 1440–51.
Vital, M.D., Fernagut, P.O. and Canron, M.H. (2009). The nigrostriatal pathway in Creutzfeldt-Jakob disease. The American Association of Neuropathologists, 68(7), 809–15.
Voorhees, J.R., Rohlman, D.S. and Lein, P.J. (2017). Neurotoxicity in preclinical models of occupational exposure to organophosphorus compounds. Frontiers in Neuroscience, 10(590), 1–24. 
Wang, A., Cockburn, M. and Ly, T.T. (2014). The association between ambient exposure to organophosphates and Parkinson’s disease risk. Occup Environment Medicine, 71(4), 275–81.
Zhang, L., Chopp, M., Jiang, Q. and Zhang, Z. (2019). Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function. Stroke Vasc Neurol., 4(2)90–2.