Skip to main content
SpringerLink
Log in

Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Earlier, protective role of curcumin in arsenic-induced dopamine (DA)–D2 receptor dysfunctions in corpus striatum has been demonstrated by us. In continuation to that, the present study is focused to decipher the molecular mechanisms associated with alterations in dopaminergic signaling on arsenic exposure in corpus striatum and assess the protective efficacy of curcumin. Exposure to arsenic (20 mg/kg, body weight p.o. for 28 days) in rats resulted to decrease the expression of presynaptic proteins-tyrosine hydroxylase and VMAT2 while no effect was observed on the expression of DAT in comparison to controls. A significant decrease in the expression of DA-D2 receptors associated with alterations in the expression of PKA, pDARPP32 (Thr 34), and PP1 α was clearly evident on arsenic exposure. Expression of BDNF and pGSK3β in corpus striatum was found decreased in arsenic-exposed rats. Simultaneous treatment with curcumin (100 mg/kg, body weight p.o. for 28 days) resulted to protect arsenic-induced alterations in the expression of DA-D2 receptors, PKA, pDARPP32, pCREB, and pPP1α. Neuroprotective efficacy of curcumin can possibly be attributed to its antioxidant potential which significantly protected arsenic-induced mitochondrial dysfunctions by modulating the ROS generation and apoptosis. Modulation in the expression of BDNF and pGSK3β in corpus striatum by curcumin exhibits the importance of neuronal survival pathway in arsenic-induced dopaminergic dysfunctions. Interestingly, curcumin was also found to protect arsenic-induced ultrastructural changes in corpus striatum. The results exhibit that curcumin modulates BDNF/DARPP32/CREB in arsenic-induced alterations in dopaminergic signaling in rat corpus striatum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Fujihara J, Yasuda T, Kato H, Yuasa I, Panduro A, Kunito T, Takeshita H (2011) Genetic variants associated with arsenic metabolism within human arsenic (+ 3 oxidation state) methyltransferase show wide variation across multiple populations. Arch Toxicol 85(2):119–125

    Article  CAS  PubMed  Google Scholar 

  2. Joseph T, Dubey B, McBean EA (2015) A critical review of arsenic exposures for Bangladeshi adults. Sci Total Environ 527:540–551

    Article  PubMed  Google Scholar 

  3. Matschullat J (2000) Arsenic in the geosphere—a review. Sci Total Environ 249(1):297–312

    Article  CAS  PubMed  Google Scholar 

  4. Hughes MF (2002) Arsenic toxicity and potential mechanisms of action. Toxicol Lett 133(1):1–16

    Article  CAS  PubMed  Google Scholar 

  5. Mukherjee A, Sengupta MK, Hossain MA, Ahamed S, Das B, Nayak B, Lodh D, Rahman MM, et al. (2006) Arsenic contamination in groundwater: a global perspective with emphasis on the Asian scenario. J Health Popul Nutr 142–163

  6. Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environmental Health Perspectives (Online) 121(3):295

    CAS  Google Scholar 

  7. Meharg AA, Rahman MM (2003) Arsenic contamination of Bangladesh paddy field soils: implications for rice contribution to arsenic consumption. Environmental Science & Technology 37(2):229–234

    Article  CAS  Google Scholar 

  8. Efferth T, Li PC, Konkimalla VSB, Kaina B (2007) From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 13(8):353–361

    Article  CAS  PubMed  Google Scholar 

  9. Smith C, Livingston S, Doolittle D (1997) An international literature survey of “IARC Group I carcinogens” reported in mainstream cigarette smoke. Food Chem Toxicol 35(10):1107–1130

    Article  CAS  PubMed  Google Scholar 

  10. ATSDR U (2007) Toxicological profile for arsenic. Agency for Toxic Substances and Disease Registry. Division of Toxicology, Atlanta, GA

    Google Scholar 

  11. Tsuji JS, Perez V, Garry MR, Alexander DD (2014) Association of low-level arsenic exposure in drinking water with cardiovascular disease: a systematic review and risk assessment. Toxicology 323:78–94

    Article  CAS  PubMed  Google Scholar 

  12. Wang S-L, Chang F-H, Liou S-H, Wang H-J, Li W-F, Hsieh DP (2007) Inorganic arsenic exposure and its relation to metabolic syndrome in an industrial area of Taiwan. Environ Int 33(6):805–811

    Article  CAS  PubMed  Google Scholar 

  13. Fan Y, Jiang Y, Hu P, Chang R, Yao S, Wang B, Li X, Zhou Q, et al. (2016) Modification of association between prior lung disease and lung cancer by inhaled arsenic: a prospective occupational-based cohort study in Yunnan, China. J Expo Sci Environ Epidemiol

  14. Ferrario D, Gribaldo L, Hartung T (2016) Arsenic exposure and immunotoxicity: a review including the possible influence of age and sex. Current environmental health reports 3(1):1–12

    Article  CAS  PubMed  Google Scholar 

  15. Vibol S, Hashim JH, Sarmani S (2015) Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia. Environ Res 137:329–337

    Article  CAS  PubMed  Google Scholar 

  16. Hamadani J, Tofail F, Nermell B, Gardner R, Shiraji S, Bottai M, Arifeen S, Huda SN et al (2011) Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol 40(6):1593–1604

    Article  CAS  PubMed  Google Scholar 

  17. Rosado JL, Ronquillo D, Kordas K, Rojas O, Alatorre J, Lopez P, Garcia-Vargas G, del Carmen Caamaño M, et al. (2007) Arsenic exposure and cognitive performance in Mexican schoolchildren. Environ Health Perspect 1371–1375

  18. Tsai S-Y, Chou H-Y, The H-W, Chen C-M, Chen C-J (2003) The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence. Neurotoxicology 24(4):747–753

    Article  CAS  PubMed  Google Scholar 

  19. Mukherjee B, Bindhani B, Saha H, Sinha D, Ray MR (2014) Platelet hyperactivity, neurobehavioral symptoms and depression among Indian women chronically exposed to low level of arsenic. Neurotoxicology 45:159–167

    Article  CAS  PubMed  Google Scholar 

  20. Tyler CR, Allan AM (2014) The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: a review. Current environmental health reports 1(2):132–147

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chandravanshi LP, Yadav RS, Shukla RK, Singh A, Sultana S, Pant AB, Parmar D, Khanna VK (2014) Reversibility of changes in brain cholinergic receptors and acetylcholinesterase activity in rats following early life arsenic exposure. Int J Dev Neurosci 34:60–75

    Article  CAS  PubMed  Google Scholar 

  22. Yadav RS, Chandravanshi LP, Shukla RK, Sankhwar ML, Ansari RW, Shukla PK, Pant AB, Khanna VK (2011) Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. Neurotoxicology 32(6):760–768

    Article  CAS  PubMed  Google Scholar 

  23. Yadav RS, Sankhwar ML, Shukla RK, Chandra R, Pant AB, Islam F, Khanna VK (2009) Attenuation of arsenic neurotoxicity by curcumin in rats. Toxicol Appl Pharmacol 240(3):367–376

    Article  CAS  PubMed  Google Scholar 

  24. Srivastava P, Yadav RS, Chandravanshi LP, Shukla RK, Dhuriya YK, Chauhan LK, Dwivedi HN, Pant AB et al (2014) Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats. Toxicol Appl Pharmacol 279(3):428–440

    Article  CAS  PubMed  Google Scholar 

  25. Bardullas U, Limón-Pacheco J, Giordano M, Carrizales L, Mendoza-Trejo M, Rodríguez V (2009) Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice. Toxicol Appl Pharmacol 239(2):169–177

    Article  CAS  PubMed  Google Scholar 

  26. Kim M, Seo S, Sung K, Kim K (2014) Arsenic exposure in drinking water alters the dopamine system in the brains of C57BL/6 mice. Biol Trace Elem Res 162(1–3):175–180

    Article  CAS  PubMed  Google Scholar 

  27. Yadav RS, Shukla RK, Sankhwar ML, Patel DK, Ansari RW, Pant AB, Islam F, Khanna VK (2010) Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats. Neurotoxicology 31(5):533–539

    Article  CAS  PubMed  Google Scholar 

  28. Epstein J, Sanderson IR, MacDonald TT (2010) Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr 103(11):1545–1557

    Article  CAS  PubMed  Google Scholar 

  29. Jagatha B, Mythri RB, Vali S, Bharath MS (2008) Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson’s disease explained via in silico studies. Free Radic Biol Med 44(5):907–917

    Article  CAS  PubMed  Google Scholar 

  30. Tripanichkul W, Jaroensuppaperch E (2013) Ameliorating effects of curcumin on 6-OHDA-induced dopaminergic denervation, glial response, and SOD1 reduction in the striatum of hemiparkinsonian mice. Eur Rev Med Pharmacol Sci 17(10):1360–1368

    CAS  PubMed  Google Scholar 

  31. Kulkarni S, Dhir A (2010) An overview of curcumin in neurological disorders. Indian journal of pharmaceutical sciences 72(2):149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu J-J, Pei L-B, Zhang Y, Wen Z-Y, Yang J-L (2015) Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 35(4):406–410

    CAS  PubMed  Google Scholar 

  33. Lopresti AL, Maes M, Meddens MJ, Maker GL, Arnoldussen E, Drummond PD (2015) Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change. Eur Neuropsychopharmacol 25(1):38–50

    Article  CAS  PubMed  Google Scholar 

  34. Al-Karawi D, Mamoori A, Alem D, Tayyar Y (2016) The role of curcumin administration in patients with major depressive disorder: mini meta-analysis of clinical trials. Phytother Res 30(2):175–183

    Article  CAS  PubMed  Google Scholar 

  35. Glowinski J, Iversen L (1966) Regional studies of catecholamines in rat brain. 3. Subcellullar distribution of endogenous and exogenous catecholamines in various brain regions. Biochem Pharmacol 15(7):977–97&

    Article  CAS  PubMed  Google Scholar 

  36. Bagh MB, Maiti AK, Jana S, Banerjee K, Roy A, Chakrabarti S (2008) Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson’s disease. Free Radic Res 42(6):574–581

    Article  CAS  PubMed  Google Scholar 

  37. Socci D, Bjugstad K, Jones H, Pattisapu J, Arendash G (1999) Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Exp Neurol 155(1):109–117

    Article  CAS  PubMed  Google Scholar 

  38. Kapoor N, Pant AB, Dhawan A, Dwievedi UN, Gupta YK, Seth PK, Parmar D (2006) Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol. Life Sci 79(16):1514–1522

    Article  CAS  PubMed  Google Scholar 

  39. Hatefi Y (1978) [1] Introduction—preparation and properties of the enzymes and enzyme complexes of the mitochondrial oxidative phosphorylation system. Methods Enzymol 53:3–4

    Article  CAS  PubMed  Google Scholar 

  40. Clark J, Bates T, Boakye P, Kuimov A, Land J (1997) Investigation of mitochondrial defects in brain and skeletal muscle. In: Neurochemistry: a practical approach. Oxford University Press Oxford, pp 151–174

  41. Wharton DC, Tzagoloff A (1967) [45] Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10:245–250

    Article  CAS  Google Scholar 

  42. Ulmer VerlagLowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with Folin-phenol reagent. J Biol Chem 193:265275

    Google Scholar 

  43. Beaulieu J-M, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182–217

    Article  CAS  PubMed  Google Scholar 

  44. Jones DC, Miller GW (2008) The effects of environmental neurotoxicants on the dopaminergic system: a possible role in drug addiction. Biochem Pharmacol 76(5):569–581

    Article  CAS  PubMed  Google Scholar 

  45. De Mei C, Ramos M, Iitaka C, Borrelli E (2009) Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol 9(1):53–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang M, Creese I (1993) Antisense oligodeoxynucleotide reduces brain dopamine D2 receptors: behavioral correlates. Neurosci Lett 161(2):223–226

    Article  CAS  PubMed  Google Scholar 

  47. Rodríguez VM, Limón-Pacheco JH, Carrizales L, Mendoza-Trejo MS, Giordano M (2010) Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat. Neurotoxicol Teratol 32(6):640–647

    Article  PubMed  Google Scholar 

  48. Listos J, Baranowska-Bosiacka I, Talarek S, Listos P, Orzelska J, Fidecka S, Gutowska I, Kolasa A et al (2013) The effect of perinatal lead exposure on dopamine receptor D2 expression in morphine dependent rats. Toxicology 310:73–83

    Article  CAS  PubMed  Google Scholar 

  49. Greengard P, Allen PB, Nairn AC (1999) Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 23(3):435–447

    Article  CAS  PubMed  Google Scholar 

  50. Cordova FM, Aguiar AS Jr, Peres TV, Lopes MW, Gonçalves FM, Remor AP, Lopes SC, Pilati C et al (2012) In vivo manganese exposure modulates Erk, Akt and Darpp-32 in the striatum of developing rats, and impairs their motor function. PLoS One 7(3):e33057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Svenningsson P, Lindskog M, Ledent C, Parmentier M, Greengard P, Fredholm BB, Fisone G (2000) Regulation of the phosphorylation of the dopamine-and cAMP-regulated phosphoprotein of 32 kDa in vivo by dopamine D1, dopamine D2, and adenosine A2A receptors. Proc Natl Acad Sci 97(4):1856–1860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rodrıguez V, Carrizales L, Jimenez-Capdeville M, Dufour L, Giordano M (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55(2):301–308

    Article  PubMed  Google Scholar 

  53. Tadanobu I, Zhang YF, Shigeo M, Hiroko S, Hiromichi N, Hiroki M, Yuichi S, Eiichi A (1990) The effect of arsenic trioxide on brain monoamine metabolism and locomotor activity of mice. Toxicol Lett 54(2–3):345–353

    Article  Google Scholar 

  54. Delgado J, Dufour L, Grimaldo J, Carrizales L, Rodrıguez V, Jimenez-Capdeville M (2000) Effects of arsenite on central monoamines and plasmatic levels of adrenocorticotropic hormone (ACTH) in mice. Toxicol Lett 117(1):61–67

    Article  CAS  PubMed  Google Scholar 

  55. Vahidnia A, van der Straaten R, Romijn F, Van Pelt J, van der Voet G, de Wolff F (2007) Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity. Toxicol in Vitro 21(6):1104–1112

    Article  CAS  PubMed  Google Scholar 

  56. Li X, Zhang H, Niu Q, Yuan F (2012) Changes of cdk5, p35 and p53 gene expression levels in arsenic-induced neural cell apoptosis. Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi= Chinese journal of industrial hygiene and occupational diseases 30(2):85–88

    PubMed  Google Scholar 

  57. Bibb JA, Chen J, Taylor JR, Svenningsson P, Nishi A, Snyder GL, Yan Z, Sagawa ZK et al (2001) Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410(6826):376–380

    Article  CAS  PubMed  Google Scholar 

  58. Sakamoto K, Karelina K, Obrietan K (2011) CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem 116(1):1–9

    Article  CAS  PubMed  Google Scholar 

  59. Sun B-F, Wang Q-Q, Yu Z-J, Yu Y, Xiao C-L, Kang C-S, Ge G, Linghu Y et al (2015) Exercise prevents memory impairment induced by arsenic exposure in mice: implication of hippocampal BDNF and CREB. PLoS One 10(9):e0137810

    Article  PubMed  PubMed Central  Google Scholar 

  60. Sriram K, Lin GX, Jefferson AM, Roberts JR, Chapman RS, Chen BT, Soukup JM, Ghio AJ et al (2010) Dopaminergic neurotoxicity following pulmonary exposure to manganese-containing welding fumes. Arch Toxicol 84(7):521–540

    Article  CAS  PubMed  Google Scholar 

  61. Choi W-S, Kim H-W, Xia Z (2015) JNK inhibition of VMAT2 contributes to rotenone-induced oxidative stress and dopamine neuron death. Toxicology 328:75–81

    Article  CAS  PubMed  Google Scholar 

  62. Ho PW, Ho JW, Liu H-F, So DH, Zero H, Chan K-H, Ramsden DB, Ho S-L (2012) Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease. Translational neurodegeneration 1(1):1

  63. Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, Surmeier DJ (2010) Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468(7324):696–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dwivedi N, Mehta A, Yadav A, Binukumar B, Gill KD, Flora SJ (2011) MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats. Toxicol Appl Pharmacol 256(3):241–248

    Article  CAS  PubMed  Google Scholar 

  65. Baquet ZC, Gorski JA, Jones KR (2004) Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J Neurosci 24(17):4250–4258

    Article  CAS  PubMed  Google Scholar 

  66. Kumar TP, Antony S, Gireesh G, George N, Paulose C (2010) Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats. J Biomed Sci 17(1):1

    Article  Google Scholar 

  67. Hickey MA, Zhu C, Medvedeva V, Lerner RP, Patassini S, Franich NR, Maiti P, Frautschy SA et al (2012) Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington’s disease. Mol Neurodegener 7(1):1

    Article  Google Scholar 

  68. Du X-X, Xu H-M, Jiang H, Song N, Wang J, Xie J-X (2012) Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease. Neurosci Bull 28(3):253–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jiang T, Wang L, Zhang S, Sun P-C, Ding C-F, Chu Y-Q, Zhou P (2011) Interaction of curcumin with Al (III) and its complex structures based on experiments and theoretical calculations. J Mol Struct 1004(1):163–173

    Article  CAS  Google Scholar 

  70. Jiang T, Zhi X-L, Zhang Y-H, Pan L-F, Zhou P (2012) Inhibitory effect of curcumin on the Al (III)-induced Aβ 42 aggregation and neurotoxicity in vitro. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1822(8):1207–1215

    Article  CAS  Google Scholar 

  71. 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 150:39–47

    Article  PubMed  Google Scholar 

  72. Kunwar A, Priyadarsini KI (2016) Curcumin and its role in chronic diseases. In: Gupta SC, Prasad S, Aggarwal BB (eds) Anti-inflammatory nutraceuticals and chronic diseases. Springer International Publishing, Cham, pp. 1–25. doi:10.1007/978-3-319-41334-1_1

    Google Scholar 

  73. Goozee K, Shah T, Sohrabi HR, Rainey-Smith S, Brown B, Verdile G, Martins R (2016) Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. Br J Nutr 115(03):449–465

    Article  CAS  PubMed  Google Scholar 

  74. Dairam A, Limson JL, Watkins GM, Antunes E, Daya S (2007) Curcuminoids, curcumin, and demethoxycurcumin reduce lead-induced memory deficits in male Wistar rats. J Agric Food Chem 55(3):1039–1044

    Article  CAS  PubMed  Google Scholar 

  75. Lv H, Liu J, Wang L, Zhang H, Yu S, Li Z, Jiang F, Niu Y et al (2014) Ameliorating effects of combined curcumin and desferrioxamine on 6-OHDA-induced rat mode of Parkinson’s disease. Cell Biochem Biophys 70(2):1433–1438

    Article  CAS  PubMed  Google Scholar 

  76. Gao S, Duan X, Wang X, Dong D, Liu D, Li X, Sun G, Li B (2013) Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 59:739–747

    Article  CAS  PubMed  Google Scholar 

  77. Nicolson GL (2013) Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Altern Ther Health Med 20(1):18–25

    Google Scholar 

  78. Pan J, Li H, Ma J-F, Tan Y-Y, Xiao Q, Ding J-Q, Chen S-D (2012) Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease through suppressing mitochondria dysfunction. Translational neurodegeneration 1(1):1

    Article  Google Scholar 

  79. Wu J, Li Q, Wang X, Yu S, Li L, Wu X, Chen Y, Zhao J et al (2013) Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway. PLoS One 8(3):e59843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Yang C, Zhang X, Fan H, Liu Y (2009) Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 1282:133–141

    Article  CAS  PubMed  Google Scholar 

  81. 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 fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic Res 39(10):1119–1125

    Article  CAS  PubMed  Google Scholar 

  82. Yu S, Zheng W, Xin N, Chi Z-H, Wang N-Q, Nie Y-X, Feng W-Y, Wang Z-Y (2010) Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway. Rejuvenation Res 13(1):55–64

    Article  CAS  PubMed  Google Scholar 

  83. Franco-Robles E, Campos-Cervantes A, Murillo-Ortiz BO, Segovia J, López-Briones S, Vergara P, Pérez-Vázquez V, Solís-Ortiz MS et al (2013) Effects of curcumin on brain-derived neurotrophic factor levels and oxidative damage in obesity and diabetes. Appl Physiol Nutr Metab 39(2):211–218

    Article  PubMed  Google Scholar 

  84. Baydyuk M, Xu B (2014) BDNF signaling and survival of striatal neurons. Front Cell Neurosci 8:254

    Article  PubMed  PubMed Central  Google Scholar 

  85. Wang R, Li Y-H, Xu Y, Li Y-B, Wu H-L, Guo H, Zhang J-Z, Zhang J-J et al (2010) Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons. Prog Neuro-Psychopharmacol Biol Psychiatry 34(1):147–153

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study has been carried out as a part of INDEPTH programme of Council of Scientific and Industrial Research (CSIR), New Delhi. The authors thank Director, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, for his support throughout the study and Dr. LKS Chauhan, for the help to carry out experiments involving transmission electron microscopy. Pranay Srivastava and Richa Gupta are grateful to the Council for Scientific and Industrial Research, New Delhi, for the award of Senior Research Fellowship. Technical support by Mr. B.S. Pandey is acknowledged.

Author information

Author notes

  1. Rajesh S. Yadav

    Present address: Department of Criminology and Forensic Science, School of Applied Sciences, Dr. Harisingh Gour Central University, Sagar, Madhya Pradesh, 470 003, India

Authors and Affiliations

  1. Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan; 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226 001, India

    Pranay Srivastava, Yogesh K. Dhuriya, Richa Gupta, Rajendra K. Shukla, Rajesh S. Yadav, Aditya B. Pant & Vinay K Khanna

  2. School of Pharmacy, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow, 227 015, India

    Pranay Srivastava, Richa Gupta & Hari N. Dwivedi

Authors
  1. Pranay Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yogesh K. Dhuriya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richa Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajendra K. Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajesh S. Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hari N. Dwivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aditya B. Pant
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vinay K Khanna
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vinay K Khanna.

Ethics declarations

All experiments were carried out in sync with the guidelines laid down by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forests (Government of India), New Delhi, India, and the experimental procedures were approved by the Institutional Animal Ethics Committee of CSIR-IITR, Lucknow (ITRC/IAEC/39/12).

Additional information

Highlights

• The role of DARPP32 in the neuroprotective efficacy of curcumin in arsenic induced dopaminergic alterations.

• BDNF plays a vital role in survival of striatal neurons on arsenic exposure and is involved in neuroprotective role of curcumin.

• Modulation of mitochondrial functions by curcumin to exert antioxidant effect seems to be a pertinent mechanism through which curcumin exercises its effects.

Pranay Srivastava and Yogesh K. Dhuriya contributed equally.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srivastava, P., Dhuriya, Y.K., Gupta, R. et al. Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum. Mol Neurobiol 55, 445–461 (2018). https://doi.org/10.1007/s12035-016-0288-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-0288-2

Keywords

Search

Navigation