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Inflammopharmacology

, Volume 26, Issue 5, pp 1305–1316 | Cite as

Gastrodin microinjection suppresses 6-OHDA-induced motor impairments in parkinsonian rats: insights into oxidative balance and microglial activation in SNc

  • Rasool Haddadi
  • Maryam Poursina
  • Fatemeh Zeraati
  • Forough Nadi
Original Article

Abstract

Purpose of the research

In this study, we appraised the effect of pre-treatment with intra-cerebro ventricular (i.c.v) microinjection of gastrodin (Gst) on catalepsy, motor imbalance, substantia nigra pars compacta (SNc) myeloperoxidase (MPO) activity, lipid peroxidation levels, nitric oxide (NO) production and total antioxidant capacity (TAC) in 6-hydroxydopamine (6-OHDA) rats model of PD.

Materials and methods

Male Wistar rats were pre-treated with i.c.v microinjections of Gst (20, 40 and 80 μg/3 μl/rat) for five consecutive days. Then, catalepsy and motor balance were induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat) into the SNc. The anti-cataleptic and motor balance improving effect of Gst was assessed by the Bar test and Rotarod 3 weeks after neurotoxin injection, respectively. SNc MPO activity and lipid peroxidation levels, NO production and TAC were assessed at the end of behavioral experiments.

Results

Our data demonstrated that Gst pre-treatment significantly (p < 0.001) was prevented motor in-coordination and catalepsy in neurotoxin lesioned rats. The most motor improving effect was seen at 80 μg Gst (p < 0.001). Pre-treatment of parkinsonian rats with Gst meaningfully (p < 0.001) was suppressed MPO activity, lipid peroxidation and NO production. Furthermore, the TAC level in the SNc was increased (p < 0.001) in Gst-microinjected rats about to the normal non-parkinsonian animals.

Major conclusions

In summary, pre-treatment with Gst abolished 6-OHDA-induced catalepsy and improved motor incoordination by decreasing: SNc MPO activity, lipid peroxidation levels and NO production, and restoring SNc levels of TAC to the levels of healthy rats.

Graphical abstract

Keywords

Gastrodin Catalepsy Rotarod Myeloperoxidase MDA Parkinson disease Rat 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

References

  1. Benzie IF, Strain J (1999) [2] Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 299:15–27CrossRefGoogle Scholar
  2. Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR (2015) Oxidative stress and Parkinson’s disease. Front Neuroanat 9:91PubMedPubMedCentralGoogle Scholar
  3. Block M, Hong J (2007) Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem Soc Trans 35:1127–1132CrossRefGoogle Scholar
  4. Blum D, Torch S, Lambeng N, Nissou M-F, Benabid A-L, Sadoul R, Verna J-M (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65:135–172CrossRefGoogle Scholar
  5. Choi DK et al (2005) Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson’s disease in mice. J Neurosci 25:6594–6600CrossRefGoogle Scholar
  6. Cohen G (1994) Free radicals, oxidative stress and neurodegeneration. In: Calne DB (ed) Neurodegenerative diseases. W. B Saunders, Philadelphia, pp 139–161Google Scholar
  7. Cohen G (2000) Oxidative stress, mitochondrial respiration, and Parkinson’s disease. Ann N Y Acad Sci 899:112–120CrossRefGoogle Scholar
  8. Dai J-N et al (2011) Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS ONE 6:e21891CrossRefGoogle Scholar
  9. de Lau LM, Breteler M (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5:525–535CrossRefGoogle Scholar
  10. Dexter DT, Jenner P (2013) Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 62:132–144.  https://doi.org/10.1016/j.freeradbiomed.2013.01.018 CrossRefPubMedGoogle Scholar
  11. Doo A-R et al (2014) Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson’s disease mouse model. BMC Complement Altern Med 14:107CrossRefGoogle Scholar
  12. Green PS, Mendez AJ, Jacob JS, Crowley JR, Growdon W, Hyman BT, Heinecke JW (2004) Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease. J Neurochem 90:724–733CrossRefGoogle Scholar
  13. Haddadi R, Mohajjel Nayebi A, Brooshghalan SE (2013) Pre-treatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats. Neurosci Lett 555:106–111CrossRefGoogle Scholar
  14. Haddadi R, Nayebi AM, Farajniya S, Brooshghalan SE, Sharifi H (2014) Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: behavioral and molecular study DARU. J Pharm Sci 22:38Google Scholar
  15. Haddadi R, Brooshghalan SE, Farajniya S, Nayebi AM, Sharifi H (2015) Short-term treatment with silymarin improved 6-OHDA-induced catalepsy and motor imbalance in hemi-parkisonian rats. Adv Pharm Bull 5:463–469.  https://doi.org/10.15171/apb.2015.063 CrossRefPubMedPubMedCentralGoogle Scholar
  16. He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909:187–193CrossRefGoogle Scholar
  17. Hwang O (2013) Role of oxidative stress in Parkinson’s disease. Exp Neurobiol 22:11–17CrossRefGoogle Scholar
  18. Iancu R, Mohapel P, Brundin P, Paul G (2005) Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson’s disease in mice. Behav Brain Res 162:1–10CrossRefGoogle Scholar
  19. Ikawa M et al (2017) Dopaminergic neuronal oxidative stress is increased with disease progression in patients with Parkinson’s disease: a study with PET and SPECT: P4. 027Google Scholar
  20. Jiang G, Hu Y, Liu L, Cai J, Peng C, Li Q (2014) Gastrodin protects against MPP+-induced oxidative stress by up regulates heme oxygenase-1 expression through p38 MAPK/Nrf2 pathway in human dopaminergic cells. Neurochem Int 75:79–88CrossRefGoogle Scholar
  21. Kheradmand A, Mohajjel Nayebi A, Jorjani M, Haddadi R (2016a) Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats. Iran J Basic Med Sci 19:490–496PubMedPubMedCentralGoogle Scholar
  22. Kheradmand A, Nayebi AM, Jorjani M, Khalifeh S, Haddadi R (2016b) Effects of WR1065 on 6-hydroxydopamine-induced motor imbalance: possible involvement of oxidative stress and inflammatory cytokines. Neurosci Lett 627:7–12.  https://doi.org/10.1016/j.neulet.2016.05.040 CrossRefPubMedGoogle Scholar
  23. Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 20:6309–6316CrossRefGoogle Scholar
  24. Kumar H, Kim I-S, More SV, Kim B-W, Bahk Y-Y, Choi D-K (2013) Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson’s disease model. Evid-Based Complement Altern Med 2013:514095CrossRefGoogle Scholar
  25. Lefkowitz DL, Lefkowitz SS (2008) Microglia and myeloperoxidase: a deadly partnership in neurodegenerative disease. Free Radic Biol Med 45:726–731CrossRefGoogle Scholar
  26. Li C, Chen X, Zhang N, Song Y, Mu Y (2012) Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson’s disease model rats. Neural Regen Res 7:325PubMedPubMedCentralGoogle Scholar
  27. Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7CrossRefGoogle Scholar
  28. Loeffler DA, Klaver AC, Coffey MP, Aasly JO, LeWitt PA (2017) Increased oxidative stress markers in cerebrospinal fluid from healthy subjects with parkinson’s disease-associated LRRK2 gene mutations. Front Aging Neurosci 9:89CrossRefGoogle Scholar
  29. McGeer P, Itagaki S, Boyes B, McGeer E (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285CrossRefGoogle Scholar
  30. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71CrossRefGoogle Scholar
  31. Mosley RL et al (2006) Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281CrossRefGoogle Scholar
  32. Olson JK, Miller SD (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173:3916–3924CrossRefGoogle Scholar
  33. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic press, San DiegoGoogle Scholar
  34. Peng Z et al (2015) Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway. Neurochem Res 40:661–673CrossRefGoogle Scholar
  35. Puthalakath H et al (2007) ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129:1337–1349CrossRefGoogle Scholar
  36. Reynolds WF, Rhees J, Maciejewski D, Paladino T, Sieburg H, Maki RA, Masliah E (1999) Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease. Exp Neurol 155:31–41CrossRefGoogle Scholar
  37. Schapira A, Cooper J, Dexter D, Clark J, Jenner P, Marsden C (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827CrossRefGoogle Scholar
  38. Sharifi H, Nayebi A, Farajnia S, Haddadi R (2014) Effect of chronic administration of buspirone and fluoxetine on inflammatory cytokines in 6-hydroxydopamine-lesioned rats. Drug Res. 64:1–5CrossRefGoogle Scholar
  39. Sharifi H, Nayebi AM, Farajnia S, Haddadi R (2015) Effect of buspirone, fluoxetine and 8-OH-DPAT on striatal expression of bax, caspase-3 and Bcl-2 proteins in 6-hydroxydopamine-induced hemi-Parkinsonian rats. Adv Pharm Bull 5:491CrossRefGoogle Scholar
  40. Song C, Fang S, Lv G, Mei X (2013) Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord. Neural Regen Res 8:1383PubMedPubMedCentralGoogle Scholar
  41. Sugama S et al (2003) Age-related microglial activation in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 mice. Brain Res 964:288–294CrossRefGoogle Scholar
  42. Tang W, Eisenbrand G (1992) Chinese drugs of plant origin. Chem Pharmacol Tradit Mod Med.  https://doi.org/10.1007/978-3-642-73739-8 CrossRefGoogle Scholar
  43. Zhang J-S, Zhou S-F, Wang Q, Guo J-N, Liang H-M, Deng J-B, He W-Y (2016) Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer’s disease. Neuroscience 325:1–9CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Rasool Haddadi
    • 1
    • 2
  • Maryam Poursina
    • 3
  • Fatemeh Zeraati
    • 1
    • 2
  • Forough Nadi
    • 3
  1. 1.Department of Pharmacology and Toxicology, School of PharmacyHamadan University of Medical SciencesHamadanIran
  2. 2.Herbal Medicine and Natural Product Research CenterHamadan University of Medical SciencesHamadanIran
  3. 3.Students Research CenterHamadan University of Medical SciencesHamadanIran

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