Skip to main content
SpringerLink
Log in

Carnosine Exerts Neuroprotective Effect Against 6-Hydroxydopamine Toxicity in Hemiparkinsonian Rat

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is the second most common disorder of the central nervous system due to the degeneration of mesencephalic dopaminergic neurons. Current treatments for PD have a symptomatic relief strategy with no prevention of disease progression. Due to the neuroprotective and antiapoptotic potential of the natural dipeptide carnosine, this study was conducted to assess its beneficial effect in 6-hydroxydopamine (6-OHDA)-induced model of PD in rat. Unilateral intrastriatal 6-OHDA-lesioned rats received i.p. carnosine at a dose of 250 mg/kg twice at an interval of 24 h, which started presurgery. Apomorphine caused contralateral rotations, a significant reduction in the number of Nissl-stained neurons on the left side of the substantia nigra, and increased apoptosis was observed with enhanced oxidative stress burden in 6-OHDA-lesioned rats. Carnosine pretreatment significantly reduced rotations, attenuated apoptosis, and restored malondialdehyde and nitrite content and catalase activity with no significant effect on reduced glutathione (GSH). These results indicate that prelesion administration of carnosine could exert neuroprotection against 6-OHDA toxicity, and this may be of benefit in patients with early PD.

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

Similar content being viewed by others

References

  1. Reeve A et al (2014) Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res Rev 14C:19–30

    Article  Google Scholar 

  2. Lindgren HS, Dunnett SB (2012) Cognitive dysfunction and depression in Parkinson’s disease: what can be learned from rodent models? Eur J Neurosci 35:1894–1907

    Article  PubMed  Google Scholar 

  3. Foltynie T, Kahan J (2013) Parkinson’s disease: an update on pathogenesis and treatment. J Neurol 260:1433–1440

    Article  CAS  PubMed  Google Scholar 

  4. Ossig C, Reichmann H (2013) Treatment of Parkinson’s disease in the advanced stage. J Neural Transm 120:523–529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Pyo JH et al (2013) Neuroprotective effect of trans-cinnamaldehyde on the 6-hydroxydopamine-induced dopaminergic injury. Biol Pharm Bull 36:1928–1935

    Article  CAS  PubMed  Google Scholar 

  6. Tatton WG et al (2003) Apoptosis in Parkinson’s disease: signals for neuronal degradation. Ann Neurol 53(Suppl 3):S61–70, discussion S70-62

    Article  CAS  PubMed  Google Scholar 

  7. Lev N et al (2003) Apoptosis and Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 27:245–250

    Article  CAS  PubMed  Google Scholar 

  8. Baluchnejadmojarad T et al (2010) Neuroprotective effect of silymarin in 6-hydroxydopamine hemi-parkinsonian rat: involvement of estrogen receptors and oxidative stress. Neurosci Lett 480:206–210

    Article  CAS  PubMed  Google Scholar 

  9. Roghani M et al (2010) Oral pelargonidin exerts dose-dependent neuroprotection in 6-hydroxydopamine rat model of hemi-parkinsonism. Brain Res Bull 82:279–283

    Article  CAS  PubMed  Google Scholar 

  10. Seidl SE et al (2014) The emerging role of nutrition in Parkinson’s disease. Front Aging Neurosci 6:36

    Article  PubMed Central  PubMed  Google Scholar 

  11. Boldyrev AA et al (2013) Physiology and pathophysiology of carnosine. Physiol Rev 93:1803–1845

    Article  CAS  PubMed  Google Scholar 

  12. Sale C et al (2013) Carnosine: from exercise performance to health. Amino Acids 44:1477–1491

    Article  CAS  PubMed  Google Scholar 

  13. Davinelli S et al (2013) Synergistic effect of l-carnosine and EGCG in the prevention of physiological brain aging. Curr Pharm Des 19:2722–2727

    Article  CAS  PubMed  Google Scholar 

  14. Ma J et al (2012) Protective effect of carnosine on subcortical ischemic vascular dementia in mice. CNS Neurosci Ther 18:745–753

    Article  CAS  PubMed  Google Scholar 

  15. Tsai SJ et al (2010) Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice. J Agric Food Chem 58:11510–11516

    Article  CAS  PubMed  Google Scholar 

  16. Oh YM et al (2009) Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by l-carnosine in SH-SY5Y cells. Neurosci Lett 459:7–10

    Article  CAS  PubMed  Google Scholar 

  17. Boldyrev A et al (2008) Carnosine [corrected] increases efficiency of DOPA therapy of Parkinson’s disease: a pilot study. Rejuvenation Res 11:821–827

    Article  CAS  PubMed  Google Scholar 

  18. Bellia F et al (2011) Neuroprotective features of carnosine in oxidative driven diseases. Mol Aspects Med 32:258–266

    Article  CAS  PubMed  Google Scholar 

  19. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, San Diego

    Google Scholar 

  20. Sedaghat R et al (2014) Neuroprotective effect of thymoquinone, the Nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res 13:227–234

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Pekcetin C et al (2009) Carnosine attenuates oxidative stress and apoptosis in transient cerebral ischemia in rats. Acta Biol Hung 60:137–148

    Article  CAS  PubMed  Google Scholar 

  22. Baluchnejadmojarad T, Roghani M (2011) Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress. Behav Brain Res 224:305–310

    Article  CAS  PubMed  Google Scholar 

  23. Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC, Boca Raton, pp 283–284

    Google Scholar 

  24. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  25. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  26. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  27. Morroni F et al (2013) Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease. Neurotoxicology 36:63–71

    Article  CAS  PubMed  Google Scholar 

  28. Jalali-Nadoushan M, Roghani M (2013) Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism. Brain Res 1505:68–74

    Article  CAS  PubMed  Google Scholar 

  29. Roghani M, Behzadi G (2001) Neuroprotective effect of vitamin E on the early model of Parkinson’s disease in rat: behavioral and histochemical evidence. Brain Res 892:211–217

    Article  CAS  PubMed  Google Scholar 

  30. Chou VP et al (2014) Gene-environment interaction models to unmask susceptibility mechanisms in Parkinson’s disease. J Vis Exp

  31. Schober A (2004) Classic toxin-induced animal models of Parkinson’s disease: 6-OHDA and MPTP. Cell Tissue Res 318:215–224

    Article  PubMed  Google Scholar 

  32. Schwarting RK, Huston JP (1997) Behavioral and neurochemical dynamics of neurotoxic meso-striatal dopamine lesions. Neurotoxicology 18:689–708

    CAS  PubMed  Google Scholar 

  33. Foley P, Riederer P (2000) Influence of neurotoxins and oxidative stress on the onset and progression of Parkinson’s disease. J Neurol 247(Suppl 2):II82–94

    PubMed  Google Scholar 

  34. Lotharius J, Brundin P (2002) Pathogenesis of Parkinson’s disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci 3:932–942

    Article  CAS  PubMed  Google Scholar 

  35. Von Bohlen und Halbach O et al (2004) Genes, proteins, and neurotoxins involved in Parkinson’s disease. Prog Neurobiol 73:151–177

    Article  Google Scholar 

  36. Chen S, Le W (2006) Neuroprotective therapy in Parkinson disease. Am J Ther 13:445–457

    Article  PubMed  Google Scholar 

  37. Zhou F et al (2007) Iptakalim alleviates rotenone-induced degeneration of dopaminergic neurons through inhibiting microglia-mediated neuroinflammation. Neuropsychopharmacology 32:2570–2580

    Article  CAS  PubMed  Google Scholar 

  38. Miklossy J et al (2006) Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys. Exp Neurol 197:275–283

    Article  CAS  PubMed  Google Scholar 

  39. Sriram K, O’Callaghan JP (2007) Divergent roles for tumor necrosis factor-alpha in the brain. J Neuroimmune Pharmacol 2:140–153

    Article  PubMed  Google Scholar 

  40. Hwang CK, Chun HS (2012) Isoliquiritigenin isolated from licorice Glycyrrhiza uralensis prevents 6-hydroxydopamine-induced apoptosis in dopaminergic neurons. Biosci Biotechnol Biochem 76:536–543

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research study was the result of a MD thesis project approved and financially supported by Shahed University in 2011.

Author information

Authors and Affiliations

  1. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Siamak Afshin-Majd, Mohsen Khalili & Mehrdad Roghani

  2. School of Medicine, Shahed University, Tehran, Iran

    Narges Mehranmehr

  3. School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Tourandokht Baluchnejadmojarad

Authors
  1. Siamak Afshin-Majd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohsen Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehrdad Roghani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Narges Mehranmehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tourandokht Baluchnejadmojarad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehrdad Roghani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afshin-Majd, S., Khalili, M., Roghani, M. et al. Carnosine Exerts Neuroprotective Effect Against 6-Hydroxydopamine Toxicity in Hemiparkinsonian Rat. Mol Neurobiol 51, 1064–1070 (2015). https://doi.org/10.1007/s12035-014-8771-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8771-0

Keywords

Search

Navigation