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Curcumin restores rotenone induced depressive-like symptoms in animal model of neurotoxicity: assessment by social interaction test and sucrose preference test

  • Syeda Madiha
  • Saida Haider
Original Article
  • 25 Downloads

Abstract

Environmental toxin rotenone has been associated to with increased Parkinson’s disease (PD) prevalence in population. Depression is one of the main non-motor symptoms of PD. Curcumin exhibits neuroprotective action in neurodegenerative diseases. In the study we investigated the effect of pre- and post-treatment of curcumin on rotenone-induced depressive-like behaviors and neurotransmitter alterations in rat model of PD. In pre-treatment phase rats were administered with curcumin (100 mg/kg/day, p.o.) for 2 weeks. After curcumin treatment rotenone (1.5 mg/kg/day, s.c.) was administered in Pre-Cur + Rot group and rotenone alone group for 8 days. Meanwhile, in Post-Cur + Rot group rotenone was injected for 8 days in order to develop PD-like symptoms. After rotenone administration curcumin (100 mg/kg/day, p.o.) was administered in Post-Cur + Rot group for 2 weeks. Depressive-like behaviors were monitored by the forced swim test (FST), open field test (OFT), sucrose preference test (SPT) and social interaction test (SIT). Animals were decapitated after behavioral analysis, striatum and hippocampus were dissected out for neurochemical estimations. Results showed that the rotenone administration significantly (p < 0.01) produced depressive-like symptoms in all depression-related behavioral test. All these behavioral deficits were accompanied by the reduction of striatal and hippocampal neurotransmitter levels following rotenone administration. Pre- and post-treatment with curcumin significantly (p < 0.01) reversed the depressive-like behavior induced by rotenone and significantly (p < 0.01) improved neurotransmitter levels as compared to rotenone injected rats. Our results strongly suggest that normalization of neurotransmitter levels particularly highlights the antidepressant effect of curcumin against rotenone-induced depressive behavior.

Keywords

Rotenone Depression Curcumin Social interaction test Sucrose preference test 

Notes

Acknowledgements

The project was funded by the University of Karachi, Karachi, Pakistan.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aarsland D, Påhlhagen S, Ballard CG, Ehrt U, Svenningsson P (2011) Depression in Parkinson disease- epidemiology, mechanisms and management. Nat Rev Neurol 8:35–47CrossRefGoogle Scholar
  2. Ahlskog JE, Muenter MD (2001) Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 16:448–458CrossRefGoogle Scholar
  3. Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324CrossRefGoogle Scholar
  4. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306CrossRefGoogle Scholar
  5. Bocarsly ME, Barson JR, Hauca JM, Hoebel BG, Leibowitz SF, Avena NM (2012) Effects of perinatal exposure to palatable diets on body weight and sensitivity to drugs of abuse in rats. Physiol Behav 107:568–575CrossRefGoogle Scholar
  6. Casarrubea M, Sorbera F, Santangelo A, Crescimanno G (2010) Microstructure of rat behavioral response to anxiety in hole-board. Neurosci Lett 481:82–87CrossRefGoogle Scholar
  7. Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK (2004) Turmeric and curcumin: biological actions and medicinal applications. Curr Sci 87:44–53Google Scholar
  8. Chen P, Kales HC, Weintraub D, Blow FC, Jiang L, Mellow AM (2007) Antidepressant treatment of veterans with Parkinson's disease and depression: analysis of a national sample. J Geriatr Psychiatry Neurol 20:161–165CrossRefGoogle Scholar
  9. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909CrossRefGoogle Scholar
  10. Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuro-Psychopharmacol 28:435–451CrossRefGoogle Scholar
  11. Freire C, Koifman S (2012) Pesticide exposure and Parkinson’s disease: epidemiological evidence of association. Neuro Toxicology 33:947–971Google Scholar
  12. Fu S, Kurzrock R (2010) Development of curcumin as an epigenetic agent. Cancer 116:4670–4676CrossRefGoogle Scholar
  13. Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz BB (2009) Well-water consumption and Parkinson’s disease in rural California. Environ Health Perspect 117:1912–1918CrossRefGoogle Scholar
  14. Gilhotra N, Dhingra D (2010) GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice. Brain Res 1352:167–175CrossRefGoogle Scholar
  15. Greenamyre JT, Cannon JR, Drolet R, Mastroberardino PG (2010) Lessons from the rotenone model of Parkinson’s disease. Trends Pharmacol Sci 31:141–142 Google Scholar
  16. Haider S, Saleem S, Perveen T, Tabassum S, Batool Z, Sadir S, Liaquat L, Madiha S (2014) Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system. Age (Dordr) 36:1291–1302CrossRefGoogle Scholar
  17. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652CrossRefGoogle Scholar
  18. Hely MA, Morris JG, Reid WG, Trafficante R (2005) Sydney multicenter study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord 20:190–199CrossRefGoogle Scholar
  19. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600–609CrossRefGoogle Scholar
  20. Iwasaki K, Fujiwara M, Shibata S, Ueki S (1986) Changes in brain catecholamine levels following olfactory bulbectomy and the effect of acute and chronic administration of desipramine in rats. Pharmacol Biochem Behav 24:1715–1719CrossRefGoogle Scholar
  21. Iwunze MO, McEwan D (2004) Peroxynitrite interaction with curcumin solubilized in ethanolic solution. Cell Mol Biol (Noisy-le-grand) 50:749–752Google Scholar
  22. Jellinger KA (2011) Interaction between α-synuclein and other proteins in neurodegenerative disorders. ScientificWorldJournal 11:1893–1907CrossRefGoogle Scholar
  23. Kandratavicius L, Balista PA, Wolf DC, Abrao J, Evora PR, Rodrigues AJ, Chaves C, Maia-de-Oliveira JP, Leite JP, Dursun SM, Baker GB, Guimaraes FS, Hallak JE (2015) Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia. BMC Neurosci 7:16–19Google Scholar
  24. Khatri DK, Juvekar AR (2016) Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson's disease. Pharmacol Biochem Behav 150-151:39–47CrossRefGoogle Scholar
  25. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI (2005) Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology 30:1883–1894CrossRefGoogle Scholar
  26. Leentjens AF (2004) Depression in Parkinson's disease: conceptual issues and clinical challenges. J Geriatr Psychiatry Neurol 17:120–126CrossRefGoogle Scholar
  27. Lemke MR (2008) Depressive symptoms in Parkinson's disease. Eur J Neurol 15:21–25CrossRefGoogle Scholar
  28. Madiha S, Tabassum S, Batool Z, Liaquat L, Sadir S, Shahzad S, Perveen T, Haider S (2017) Assessment of gait dynamics in rotenone-induced rat model of Parkinson’s disease by footprint method. Pak J Pharm Sci 30:943–948PubMedGoogle Scholar
  29. Madiha S, Batool Z, Tabassum S, Liaquat L, Sadir S, Perveen T, Haider S (2018) Therapeutic effects of curcuma longa against rotenone-induced gross motor skills deficits in rats. Pak J Zool 50:1245–1256CrossRefGoogle Scholar
  30. Mansouri Z, Sabetkasaei M, Moradi F, Masoudnia F, Ataie A (2012) Curcumin has neuroprotection effect on homocysteine rat model of Parkinson. J Mol Neurosci 47:234–242CrossRefGoogle Scholar
  31. Mayberg HS, Solomon DH (1995) Depression in Parkinsons disease: a biochemical and organic viewpoint. Adv Neurol 65:49–60PubMedGoogle Scholar
  32. Mayeux R (1990) Depression in the patient with Parkinson's disease. J Clin Psychiatry. 51 Suppl:20–23; discussion 24–25Google Scholar
  33. Mazarati A, Shin D, Auvin S, Caplan R, Sankar R (2007) Kindling epileptogenesis in immature rats leads to persistent depressive behavior. Epilepsy Behav 10:377–383CrossRefGoogle Scholar
  34. Mazzio EA, Harris N, Soliman KF (1998) Food constituents attenuate monoamine oxidase activity and peroxide levels in C6 astrocyte cells. Planta Med 64:603–606CrossRefGoogle Scholar
  35. McDonald WM, Richard IH, DeLong MR (2003) Prevalence, etiology, and treatment of depression in Parkinson’s disease. Biol Psychiatry 54:363–375CrossRefGoogle Scholar
  36. Miller KM, Okun MS, Fernandez HF, Jacobson CE 4th, Rodriguez RL, Bowers D (2007) Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor. Mov Disord 22:666–672CrossRefGoogle Scholar
  37. Moon Y, Lee KH, Park JH, Geum D, Kim K (2005) Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. J Neurochem 93:1199–1208CrossRefGoogle Scholar
  38. Morais LH, Lima MM, Martynhak BJ, Santiago R, Takahashi TT, Ariza D, Barbiero JK, Andreatini R, Vital MA (2012) Characterization of motor, depressive-like and neurochemical alterations induced by a short-term rotenone administration. Pharmacol Rep 64:1081–1090CrossRefGoogle Scholar
  39. Nehru B, Verma R, Khanna P, Sharma SK (2008) Behavioral alterations in rotenone model of Parkinson’s disease: attenuation by co-treatment of centrophenoxine. Brain Res 1201:122–127CrossRefGoogle Scholar
  40. Porsolt RD, Bertin A, Jalfre M (1978) Behavioural despair in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294CrossRefGoogle Scholar
  41. Rajeswari A (2006) Curcumin protects mouse brain from oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Eur Rev Med Pharmacol Sci 10:157–161PubMedGoogle Scholar
  42. Rajeswari A, Sabesan M (2008) Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson's disease induced by MPTP neurodegeneration in mice. Inflammopharmacology 16:96–99CrossRefGoogle Scholar
  43. Ren Y, Feng J (2007) Rotenone selectively kills serotonergic neurons through a microtubule-dependent mechanism. J Neurochem 103:303–311PubMedGoogle Scholar
  44. Santiago RM, Barbieiro J, Lima MM, Dombrowski PA, Andreatini R, Vital MA (2010) 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 Neuro-Psychopharmacol Biol Psychiatry 34:1104–1114CrossRefGoogle Scholar
  45. Schapira AHV (2005) Present and future drug treatment for Parkinson’s disease. J Neurol Neurosurg Psychiatry 76:1472–1478CrossRefGoogle Scholar
  46. Schloss P, Henm FM (2004) New insights into the mechanisms of antidepressant therapy. Pharmacol Ther 102:47–60CrossRefGoogle Scholar
  47. Serra G, Agriolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25:415–423CrossRefGoogle Scholar
  48. Sharma N, Jamwal S, Kumar P (2016) Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats. Pathophysiology 23:123–134CrossRefGoogle Scholar
  49. Vajragupta O, Boonchoong P, Watanabe H, Tohda M, Kummasud N, Sumanont Y (2003) Manganese complexes of curcumin and its derivatives: evaluation for the radical scavenging ability and neuroprotective activity. Free Radic Biol Med 35:1632–1644CrossRefGoogle Scholar
  50. Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005) Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav 82:200–206CrossRefGoogle Scholar
  51. Yacoubian TA, Standaert DG (2009) Targets for neuroprotection in Parkinson’s disease. Biochim Biophys Acta 1792:676–687CrossRefGoogle Scholar
  52. Yamamoto M (2001) Depression in Parkinsons disease: its prevalence, diagnosis, and neurochemical background. J Neurol 248(Suppl. 3):III5–III11PubMedGoogle Scholar
  53. Yanpallewar SU, Rai S, Kumar M, Acharya SB (2004) Evaluation of antioxidant and neuroprotective effect of Ocimum sanctum on transient cerebral ischemia and long-term cerebral hypoperfusion. Pharmacol Biochem Behav 79:155–164CrossRefGoogle Scholar
  54. Zaminelli T, Gradowski RW, Bassani TB, Barbiero JK, Santiago RM, Maria-Ferreira D, Baggio CH, Vital MA (2014) Antidepressant and antioxidative effect of ibuprofen in the rotenone model of Parkinson’s disease. Neurotox Res 26:351–362CrossRefGoogle Scholar
  55. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT (2005) Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetinin a 6-OHDA model of Parkinson’s disease. Free Radic Res 39:1119–1125CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of BiochemistryUniversity of KarachiKarachiPakistan

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