Skip to main content
SpringerLink
Log in

Protective effect of curcumin against rotenone-induced substantia nigra pars compacta neuronal dysfunction

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Rotenone is involved in the degeneration of dopaminergic neurons, and curcumin may prevent or effectively slow the progression of Parkinson’s disease (PD). Previous research has shown that the naturally occurring phenolic compound curcumin can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative diseases. The present study involves investigation of rotenone-induced histological changes in the brain area, hippocampus using Nissl staining after 35 day of subcutaneous injection of rotenone in adult male rats. We sought to determine whether curcumin could protect against rotenone-induced dopaminergic neurotoxicity in a rat model by in vivo electrical recording from Substantia nigra pars compacta (SNc). Curcumin treatment significantly improved electrical activity of neurons in the SNc of rotenone-induced PD model rats. The pattern of histological alterations corresponds with electrophysiological manifestations.

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

Similar content being viewed by others

Data availability

Raw data can be provided upon request to the corresponding author.

References

  • Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59

    Article  CAS  PubMed  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histological techniques, 6th edn. Churchill Livingstone, London

    Google Scholar 

  • Bayer HM, Glimcher PW (2005) Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47:129–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breit S, Bouali-Benazzouz R, Popa RC, Gasser T, Benabid AL, Benazzouz A (2007) Effects of 6-hydroxydopamine-induced severe or partial lesion of the nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in the rat. Exp Neurol 205:36–47

    Article  CAS  PubMed  Google Scholar 

  • Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, Casida JE (2004) Rotenone, deguelin, their metabolites, and the rat model of Parkinson’s disease. Chem Res Toxicol 17:1540–1548

    Article  CAS  PubMed  Google Scholar 

  • Calabresi P, Gubellini P, Picconi B, Centonze D, Pisani A, Bonsi P, Greengard P, Hipskind RA, Borrelli E, Bernardi G (2001) Inhibition of mitochondrial complex II induces a long-term potentiation of NMDA-mediated synaptic excitation in the striatum requiring endogenous dopamine. J Neurosci 21:5110–5120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007) Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 447(7148):1081–1086

    Article  CAS  PubMed  Google Scholar 

  • Cui Q, Li X, Zhu H (2016) Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep 13:1381–1388

    Article  CAS  PubMed  Google Scholar 

  • Darbinyan LV, Hambardzumyan LE, Simonyan KV, Chavushyan VA, Manukyan LP, Badalyan SA, Khalaji N, Sarkisian VH (2017a) Protective effects of curcumin against rotenoneinduced rat model of Parkinson’s disease: in vivo electrophysiological and behavioral study. Metab Brain Dis 32(6):1791–1803

    Article  CAS  PubMed  Google Scholar 

  • Darbinyan LV, Hambardzumyan LE, Simonyan KV, Chavushyan VA, Manukyan LP, Sarkisian VH (2017b) Rotenone impairs hippocampal neuronal activity in a rat model of Parkinson's disease. Pathophysiology 24(1):23–30

    Article  CAS  PubMed  Google Scholar 

  • Darbinyan LV, Hambardzumyan LE, Simonyan KV, Chavushyan VA, Manukyan LP, Sarkisian VH (2017c) Rotenone impairs hippocampal neuronal activity in a rat model of Parkinson's disease. Pathophysiology. 24(1):23–30

    Article  CAS  PubMed  Google Scholar 

  • Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ (2012) Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 21:1123–1140

    Article  CAS  PubMed  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  PubMed  Google Scholar 

  • Ding J et al (2014) Curcumol from Rhizoma Curcumae suppresses epileptic seizure by facilitation of GABA(A) receptors. Neuropharmacology 81:244–255

    Article  CAS  PubMed  Google Scholar 

  • Drolet RE, Cannon JR, Montero L, Greenamyre JT (2009) Chronic rotenone exposure reproduces Parkinson's disease gastrointestinal neuropathology. Neurobiol Dis 36:96–102

    Article  CAS  PubMed  Google Scholar 

  • Dupuis JP, Feyder M, Miguelez C, Garcia L, Morin S, Choquet D, Hosy E, Bezard E, Fisone G, Bernard H (2013) Dopamine-Dependent Long-Term Depression at Subthalamo-Nigral Synapses Is Lost in Experimental Parkinsonism. J Neurosci 33(36):14331–14341

  • Fonck C, Nashmi R, Deshpande P, Damaj MI, Marks MJ, Riedel A, Schwarz J, Collins AC, Labarca C, Lester HA (2003) Increased sensi- tivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha-4 nicotinic receptors. J Neurosci 23:2582–2590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujiyama F, Sohn J, Nakano T, Furuta T, Nakamura KC, Matsuda W, Kaneko T (2011) Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector. Eur J Neurosci 33:668–677

    Article  PubMed  Google Scholar 

  • Gao HM, Hong JS, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci Off J Soc Neurosci 22:782–790

    Article  CAS  Google Scholar 

  • Greene JG, Noorian AR, Srinivasan S (2009) Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease. Exp Neurol 218:154–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartley A, Stone JM, Heron C, Cooper JM, Schapira AH (1994) Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson’s disease. J Neurochem 63:1987–1990

    Article  CAS  PubMed  Google Scholar 

  • Hoglinger GU, Feger J, Prigent A, Michel PP, Parain K, Champy P, Ruberg M, Oertel WH, Hirsch EC (2003) Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 84:491–502

    Article  CAS  PubMed  Google Scholar 

  • Hong S, Jhou TC, Smith M, Saleem KS, Hikosaka O (2011) Negative reward signals from the lateral habenula to dopamine neurons are mediated by rostromedial tegmental nucleus in primates. J Neurosci 31:11457–11471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kajikawa Y, Schroeder CE (2011) How local is the local field potential? Neuron 72:847–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kulkarni SK, Bhutani MK, Bishnoi M (2008) Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 201:435–442

    Article  CAS  PubMed  Google Scholar 

  • Leng A, Feldon J, Ferger B (2003) Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. Synapse 50:240–250

    Article  CAS  PubMed  Google Scholar 

  • Liu YM, Fan HR, Ding J et al (2017) Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines. Sci Rep 7:46654

    Article  PubMed  PubMed Central  Google Scholar 

  • Marsden KC, Beattie JB, Friedenthal J, Carroll RC (2007a) NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABAA receptors. J Neurosci 27(52):14326–14337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsden KC, Beattie JB, Friedenthal J, Carroll RC (2007b) NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABAA receptors. J Neurosci 27(52):14326–14337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merwe C, van Dyk H, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B et al (2017) Curcumin rescues a PINK1 Knock down SH- SY5Y cellular model of Parkinson’s disease from mitochondrial dysfunction and cell death. Mol Neurobiol 54(4):2752–2762

    Article  PubMed  CAS  Google Scholar 

  • Montague PR, Hyman SE, Cohen JD (2004) Computational roles for dopamine in behavioural control. Nature 431:760–767

    Article  CAS  PubMed  Google Scholar 

  • Moran RJ, Mallet N, Litvak V, Dolan RJ, Magill PJ, Friston KJ et al (2011) Alterations in brain connectivity underlying beta oscillations in parkinsonism. PLoS Comput Biol 7:e1002124. https://doi.org/10.1371/journal.pcbi.1002124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morikawa H, Paladini CA (2011) Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms. Neuroscience 198:95–111

    Article  CAS  PubMed  Google Scholar 

  • Mythri RB, Bharath MM (2012) Curcumin: a potential neuroprotective agent in Parkinson's disease. Curr Pharm Des 18(1):91–99

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates: compact, 6th edn. Academic Press, Cambridge

    Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, San Diego

    Google Scholar 

  • Pienaar IS, Elson JL, Racca C, Nelson G, Turnbull DM, Morris CM et al (2013) Mitochondrial abnormality associates with type-specific neuronal loss and cell morphology changes in the pedunculopontine nucleus in Parkinson disease. Am J Pathol 183:1826–1840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qualls Z, Brown D, Ramlochansingh C, Hurley LL, Tizabi Y (2014) Protective effects of curcumin against rotenone and salsolinol-induced toxicity: implications for Parkinson's disease. Neurotox Res 25(1):81–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94:79–83

    Article  CAS  PubMed  Google Scholar 

  • Senek M, Nyholm D (2014) Continuous drug delivery in Parkinson's disease. CNS Drugs 28(1):19–27

    Article  CAS  PubMed  Google Scholar 

  • Song S, Nie Q, Li Z, Du G (2016) Curcumin improves neurofunctions of 6-OHDA-induced parkinsonian rats. Pathol - Res Pract 212(4):247–251

    Article  CAS  PubMed  Google Scholar 

  • Surmeier DJ (2007) Calcium, ageing, and neuronal vulnerability in Parkinson's disease. Lancet Neurol 6(10):933–938

    Article  CAS  PubMed  Google Scholar 

  • Surmeier DJ, Mercer JN, Chan CS (2005) Autonomous pacemakers in the basal ganglia: who needs excitatory synapses anyway? Curr Opin Neurobiol 15(3):312–318

    Article  CAS  PubMed  Google Scholar 

  • Tepper JM, Lee CR (2007) GABAergic control of substantia nigra dopaminergic neurons. Prog Brain Res 160:189–208

    Article  CAS  PubMed  Google Scholar 

  • Tepper JM, Martin LP, Anderson DR (1995) GABAA receptor-mediated inhibition of rat substantia nigra dopaminergic neurons by pars reticulata projection neurons. J Neurosci 15:3092–3103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ulusoy GK, Celik T, Kayir H, Gürsoy M, Isik AT, Uzbay TI (2011) Effects of pioglitazone and retinoic acid in a rotenone model of Parkinson's disease. Brain Res Bull 85(6):380–384

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Song S, Li J, Liang T (2014) Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat. Pathol Res Pract 210:357–362

    Article  CAS  PubMed  Google Scholar 

  • Yu S, Zheng W, Xin N, Chi ZH, Wang NQ, Nie YX, Feng WY, Wang ZY (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 

Download references

Author information

Authors and Affiliations

  1. Sensorimotor Integration Laboratory, Orbeli Institute of Physiology NAS RA, 0028, Yerevan, Armenia

    L. V. Darbinyan, L. E. Hambardzumyan, L. P. Manukyan, S. H. Badalyan & V. H. Sarkisian

  2. Neuroendocrine Relationships Laboratory, Orbeli Institute of Physiology NAS RA, 0028, Yerevan, Armenia

    K. V. Simonyan

Authors
  1. L. V. Darbinyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. V. Simonyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. E. Hambardzumyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. P. Manukyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. H. Badalyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. H. Sarkisian
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study Concept and Design: L.D., K.S.,V.S. Acquisition of Data: L.D., K.S.. Analysis and Interpretation of the Data: L.D., K.S., Drafting of the Manuscript: L.D., K.S., L.H., L.M., V.S., S.B.

Corresponding author

Correspondence to K. V. Simonyan.

Ethics declarations

Ethics approval and consent to participate

The experimental protocol corresponded to the conditions of the European Communities Council Directive (2010/63/ UE) and it was approved by the Ethics committee of the Yerevan State Medical University after Mkhitar Heratsi (Approval code-N4 IRB APROVAL, November 15, 2018).

Competing interests

The authors declare no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Darbinyan, L.V., Simonyan, K.V., Hambardzumyan, L.E. et al. Protective effect of curcumin against rotenone-induced substantia nigra pars compacta neuronal dysfunction. Metab Brain Dis 37, 1111–1118 (2022). https://doi.org/10.1007/s11011-022-00941-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-022-00941-6

Keywords

Search

Navigation