Abstract
Background: Parkinson’s Disease (PD) is characterized by alterations in cerebellum and basal ganglia functioning with corresponding motor deficits and neuropsychiatric symptoms. Involvement of oxidative dysfunction has been implicated for the progression of PD, and environmental neurotoxin exposure could influence such behavior and psychiatric pathology. Assessing dietary supplementation strategies with naturally occurring phytochemicals to reduce behavioral anomalies associated with neurotoxin exposure would have major clinical importance. The present investigation assessed the influence of Bacopa monneri (BM) on behaviors considered to reflect anxiety-like state and motor function as well as selected biochemical changes in brain regions of mice chronically exposed to ecologically relevant herbicide, paraquat (PQ).
Materials & Methods: Male mice (4-week old, Swiss) were daily provided with oral supplements of standardized BM extract (200 mg/kg body weight/day; 3 weeks) and PQ (10 mg/kg, i.p. three times a week; 3 weeks).
Results: We found that BM supplementation significantly reversed the PQ-induced reduction of exploratory behavior, gait abnormalities (stride length and mismatch of paw placement) and motor impairment (rotarod performance). In a separate study, BM administration prevented the reduction in dopamine levels and reversed cholinergic activity in brain regions important for motor (striatum) pathology. Further, in mitochondria, PQ-induced decrease in succinate dehydrogenase (SDH) activity and energy charge (MTT reduction), was restored with BM supplementation.
Conclusion: These findings suggest that BM supplementation mitigates paraquat-induced behavioral deficits and brain oxidative stress in mice. However, further investigations would enable us to identify specific molecular mechanism by which BM influences behavioural pathology.
Keywords: Bacopa monnieri, phytochemicals, behavior, oxidative stress, paraquat, Parkinson's disease.
Graphical Abstract
[1]
Sherer, T.B.; Betarbet, R.; Greenamyre, J.T. Environment, mitochondria, and Parkinson’s disease. Neuroscientist, 2002, 8, 192-197.
[2]
Miller, R.L.; James-Kracke, M.; Sun, G.Y.; Sun, A.Y. Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem. Res., 2009, 34(1), 55-65.
[3]
Colle, D.; Farina, M.; Ceccatelli, S.; Raciti, M. Paraquat and maneb exposure alters rat neural stem cell proliferation by inducing oxidative stress: New insights on pesticide-induced neurodevelopmental toxicity. Neurotox. Res., 2018, 1, 14.
[4]
Zeng, X.S.; Geng, W.S.; Jia, J.J. Neurotoxin-induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro, 2018, 10, 175909141877743.
[5]
de Oliveira, M.R.; Peres, A.; Gama, C.S.; Dal Bosco, S.M. Pinocembrin provides mitochondrial protection by the activation of the Erk1/2-Nrf2 signaling pathway in SH-SY5Y neuroblastoma cells exposed to paraquat. Mol. Neurobiol., 2017, 54(8), 6018-6031.
[6]
Wills, J.; Credle, J.; Oaks, A.W.; Duka, V.; Lee, J.H.; Jones, J.; Sidhu, A. Paraquat, but not maneb, induces synucleinopathy and tauopathy in striata of mice through inhibition of proteasomal and autophagic pathways. PLoS One, 2012, 7(1), e30745.
[7]
Rappold, P.M.; Cui, M.; Chesser, A.S.; Tibbett, J.; Grima, J.C.; Duan, L.; Sen, N.; Javitch, J.A.; Tieu, K. Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc. Natl. Acad. Sci., 2011, 108(51), 20766-20771.
[8]
Miranda-Contreras, L.; Dávila-Ovalles, R.; Benítez-Díaz, P.; Peña-Contreras, Z.; Palacios-Prü, E. Effects of prenatal paraquat and mancozeb exposure on amino acid synaptic transmission in developing mouse cerebellar cortex. Dev. Brain Res., 2005, 160(1), 19-27.
[9]
Shiba, M.; Bower, J.H.; Maraganore, D.M.; McDonnell, S.K.; Peterson, B.J.; Ahlskog, J.E.; Schaid, D.J.; Rocca, W.A. Anxiety disorders and depressive disorders preceding Parkinson’s disease: A case-control study. Mov. Disord., 2000, 15(4), 669-677.
[10]
Chaudhuri, K.R.; Healy, D.G.; Schapira, A.H. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol., 2006, 5(3), 235-245.
[11]
Gilat, M.; Bell, P.T.; Martens, K.A.; Georgiades, M.J.; Hall, J.M.; Walton, C.C.; Lewis, S.J.; Shine, J.M. Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson’s disease. Neuroimage, 2017, 152, 207-220.
[12]
Grinberg, L.T.; Rueb, U.; di Lorenzo Alho, A.T.; Heinsen, H. Brainstem pathology and non-motor symptoms in PD. J. Neurol. Sci., 2010, 289(1-2), 81-88.
[13]
Maurice, N.; Liberge, M.; Jaouen, F.; Ztaou, S.; Hanini, M.; Camon, J.; Deisseroth, K.; Amalric, M.; Kerkerian-Le Goff, L.; Beurrier, C. Striatal cholinergic interneurons control motor behavior and basal ganglia function in experimental parkinsonism. Cell Reports, 2015, 13(4), 657-666.
[14]
Mishra, A.; Mishra, A.K.; Jha, S. Effect of traditional medicine brahmi vati and bacoside A-rich fraction of Bacopa monnieri on acute pentylenetetrazole-induced seizures, amphetamine-induced model of schizophrenia, and scopolamine-induced memory loss in laboratory animals. Epilepsy Behav., 2018, 80, 144-151.
[15]
Hosamani, R. Muralidhara. Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. Neurotoxicology, 2009, 30(6), 977-985.
[16]
Zu, X.; Zhang, M.; Li, W.; Xie, H.; Lin, Z.; Yang, N.; Liu, X.; Zhang, W. Antidepressant-like effect of Bacopaside I in mice exposed to chronic unpredictable mild stress by modulating the hypothalamic-pituitary-adrenal axis function and activating BDNF signaling pathway. Neurochem. Res., 2017, 42(11), 3233-3244.
[17]
Promsuban, C.; Limsuvan, S.; Akarasereenont, P.; Tilokskulchai, K.; Tapechum, S.; Pakaprot, N. Bacopa monnieri extract enhances learning-dependent hippocampal long-term synaptic potentiation. Neuroreport, 2017, 28(16), 1031-1035.
[18]
Upadhyay, P.; Sadhu, A.; Singh, P.K.; Agrawal, A.; Ilango, K.; Purohit, S.; Dubey, G.P. Revalidation of the neuroprotective effects of a United States patented polyherbal formulation on scopolamine induced learning and memory impairment in rats. Biomed. Pharmacother., 2018, 97, 1046-1052.
[19]
Singh, B.; Pandey, S.; Yadav, S.K.; Verma, R.; Singh, S.P.; Mahdi, A.A. Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic pathways of dopaminergic neurons. Brain Res. Bull., 2017, 135, 120-128.
[20]
Jadiya, P.; Khan, A.; Sammi, S.R.; Kaur, S.; Mir, S.S.; Nazir, A. Anti-Parkinsonian effects of Bacopa monnieri: Insights from transgenic and pharmacological Caenorhabditis elegans models of Parkinson’s disease. Biochem. Biophys. Res. Commun., 2011, 413(4), 605-610.
[21]
Singh, M.; Murthy, V.; Ramassamy, C. Neuroprotective mechanisms of the standardized extract of Bacopa monniera in a paraquat/diquat-mediated acute toxicity. Neurochem. Int., 2013, 62(5), 530-539.
[22]
Pandey, S.P.; Singh, H.K.; Prasad, S. Alterations in hippocampal oxidative stress, expression of AMPA receptor GluR2 subunit and associated spatial memory loss by Bacopa monnieri extract (CDRI-08) in streptozotocin-induced diabetes mellitus type 2 mice. PLoS One, 2015, 10(7), e0131862.
[23]
Thomas, R.B.; Joy, S.; Ajayan, M.S.; Paulose, C.S. Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats. Cell. Mol. Neurobiol., 2013, 33(8), 1065-1074.
[24]
Radi, R.; Beckman, J.S.; Bush, K.; Freeman, B.A. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J. Biol. Chem., 1991, 266(7), 4244-4250.
[25]
Grzelak, A.; Soszyński, M.; Bartosz, G. Inactivation of antioxidant enzymes by peroxynitrite. Scand. J. Clin. Lab. Invest., 2000, 60(4), 253-258.
[26]
Radi, R.; Cassina, A.; Hodara, R.; Quijano, C.; Castro, L. Peroxynitrite reactions and formation in mitochondria. Free Radic. Biol. Med., 2002, 33(11), 1451-1464.
[27]
Devi, L.; Ohno, M. Mitochondrial dysfunction and accumulation of the β-secretase-cleaved C-terminal fragment of APP in Alzheimer’s disease transgenic mice. Neurobiol. Dis., 2012, 45(1), 417-424.
[28]
Chen, L.; Ding, Y.; Cagniard, B.; Van Laar, A.D.; Mortimer, A.; Chi, W.; Hastings, T.G.; Kang, U.J.; Zhuang, X. Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J. Neurosci., 2008, 28(2), 425-433.
[29]
Rezin, G.T.; Amboni, G.; Zugno, A.I.; Quevedo, J.; Streck, E.L. Mitochondrial dysfunction and psychiatric disorders. Neurochem. Res., 2009, 34(6), 1021-1029.
[30]
Hosamani, R.; Krishna, G. Muralidhara. Standardized Bacopa monnieri extract ameliorates acute paraquat-induced oxidative stress, and neurotoxicity in prepubertal mice brain. Nutr. Neurosci., 2016, 19(10), 434-446.
[31]
Krishna, G. Muralidhara. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats. Neurotoxicol. Teratol., 2015, 49, 49-58.
[32]
Viaro, R.; Marti, M.; Morari, M. Dual motor response to L-dopa and nociceptin/ orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxial inhibition us relieved by D2/D3 receptor blockade. Exp. Neurol., 2010, 223(2), 473-484.
[33]
Moreadith, R.W.; Fiskum, G. Isolation of mitochondria from ascites tumor cells permeabilized with digitonin. Anal. Biochem., 1984, 137(2), 360-367.
[34]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[35]
Wolff, S.P. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol., 1994, 233, 182-189.
[37]
Guthenberg, C.; Ålin, P.; Mannervik, B. Glutathione transferase from rat testis. Methods Enzymol., 1985, 113, 507-510.
[38]
Ellman, G.L. Courtney, K.D.; Andres Jr., V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7(2), 88-95.
[39]
Dalpiaz, A.; Filosa, R.; De Caprariis, P.; Conte, G.; Bortolotti, F.; Biondi, C.; Scatturin, A.; Prasad, P.D.; Pavan, B. Molecular mechanism involved in the transport of a prodrug dopamine glycosyl conjugate. Int. J. Pharm., 2007, 336(1), 133-139.
[40]
Pennington, R.J. Biochemistry of dystrophic muscle. Mitochondrial succinate-tetrazolium reductase and adenosine triphosphatase. Biochem. J., 1961, 80(3), 649.
[41]
Berridge, M.V.; Tan, A.S. Characterization of the cellular reduction of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch. Biochem. Biophys., 1993, 303(2), 474-482.
[42]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[43]
Russo, A.; Borrelli, F. Bacopa monniera, a reputed nootropic plant: An overview. Phytomedicine, 2005, 12(4), 305-317.
[44]
Aguiar, S.; Borowski, T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res., 2013, 16(4), 313-326.
[45]
Subramaniam, S.R.; Chesselet, M.F. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog. Neurobiol., 2013, 106, 17-32.
[46]
Blesa, J.; Trigo-Damas, I.; Quiroga-Varela, A.; Jackson-Lewis, V.R. Oxidative stress and Parkinson’s disease. Front. Neuroanat., 2015, 9, 91.
[47]
Veal, E.A.; Day, A.M.; Morgan, B.A. Hydrogen peroxide sensing and signaling. Mol. Cell, 2007, 26(1), 1-14.
[48]
Cicchetti, F. Drouin-Ouellet.; Gross, R.E. Environmental toxins and Parkinson’s disease: What have we learned from pesticide-induced animal models? Trends Pharmacol. Sci., 2009, 30(9), 475-483.
[49]
Kaizer, R.R.; Corrêa, M.C.; Spanevello, R.M.; Morsch, V.M.; Mazzanti, C.M.; Gonçalves, J.F.; Schetinger, M.R. Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J. Inorg. Biochem., 2005, 99(9), 1865-1870.
[50]
Le, X.T.; Pham, H.T.N.; Do, P.T.; Fujiwara, H.; Tanaka, K.; Li, F.; Van Nguyen, T.; Nguyen, K.M.; Matsumoto, K. Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: Possible involvement of glutamatergic and cholinergic systems. Neurochem. Res., 2013, 38(10), 2201-2215.
[51]
Chung, K.A.; Lobb, B.M.; Nutt, J.G.; Horak, F.B. Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease. Neurology, 2010, 75(14), 1263-1269.
[52]
Fiskum, G.; Starkov, A.; Polster, B.M.; Chinopoulos, C. Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann. N. Y. Acad. Sci., 2003, 991(1), 111-119.
[53]
Keller, J.N.; Kindy, M.S.; Holtsberg, F.W.; Clair, D.K.S.; Yen, H.C.; Germeyer, A.; Steiner, S.M.; Bruce-Keller, A.J.; Hutchins, J.B.; Mattson, M.P. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: Suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J. Neurosci., 1998, 18(2), 687-697.
[54]
Cochemé, H.M.; Murphy, M.P. Complex I is the major site of mitochondrial superoxide production by paraquat. J. Biol. Chem., 2008, 283(4), 1786-1798.
[55]
Pawar, R.; Gopalakrishnan, C.; Bhutani, K.K. Dammarane triterpene saponin from Bacopa monniera as the superoxide inhibitor in polymorphonuclear cells. Planta Med., 2001, 67(08), 752-754.
[56]
Kowaltowski, A.J.; de Souza-Pinto, N.C.; Castilho, R.F.; Vercesi, A.E. Mitochondria and reactive oxygen species. Free Radic. Biol. Med., 2009, 47(4), 333-343.
[58]
Czerniczyniec, A.; Karadayian, A.G.; Bustamante, J.; Cutrera, R.A.; Lores-Arnaiz, S. Paraquat induces behavioral changes and cortical and striatal mitochondrial dysfunction. Free Radic. Biol. Med., 2011, 51(7), 1428-1436.
[59]
Orrenius, S.; Gogvadze, V.; Zhivotovsky, B. Mitochondrial oxidative stress: Implications for cell death. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 143-183.
[61]
Santiago, R.M.; Barbieiro, J.; Lima, M.M.; Dombrowski, P.A.; Andreatini, R.; Vital, M.A. Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson’s disease are predominantly associated with serotonin and dopamine. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(6), 1104-1114.
[62]
Carvalho, M.M.; Campos, F.L.; Coimbra, B.; Pêgo, J.M.; Rodrigues, C.; Lima, R.; Rodrigues, A.J.; Sousa, N.; Salgado, A.J. Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits. Mol. Neurodegener., 2013, 8(1), 14.
[63]
Meyer, P.M.; Strecker, K.; Kendziorra, K.; Becker, G.; Hesse, S.; Woelpl, D.; Hensel, A.; Patt, M.; Sorger, D.; Wegner, F.; Lobsien, D. Reduced α4β2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease. Arch. Gen. Psychiatry, 2009, 66(8), 866-877.
[64]
Litteljohn, D.; Mangano, E.; Shukla, N.; Hayley, S. Interferon-γ deficiency modifies the motor and co-morbid behavioral pathology and neurochemical changes provoked by the pesticide paraquat. Neuroscience, 2009, 164(4), 1894-1906.
[65]
Byler, S.L.; Boehm, G.W.; Karp, J.D.; Kohman, R.A.; Tarr, A.J.; Schallert, T.; Barth, T.M. Systemic lipopolysaccharide plus MPTP as a model of dopamine loss and gait instability in C57Bl/6J mice. Behav. Brain Res., 2009, 198(2), 434-439.
[66]
Kurz, M.J.; Pothakos, K.; Jamaluddin, S.; Scott-Pandorf, M.; Arellano, C.; Lau, Y.S. A chronic mouse model of Parkinson’s disease has a reduced gait pattern certainty. Neurosci. Lett., 2007, 429(1), 39-42.
[67]
Tinakoua, A.; Bouabid, S.; Faggiani, E.; De Deurwaerdère, P.; Lakhdar-Ghazal, N.; Benazzouz, A. The impact of combined administration of paraquat and maneb on motor and non-motor functions in the rat. Neuroscience, 2015, 311, 118-129.
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