Hostname: page-component-76fb5796d-vfjqv Total loading time: 0 Render date: 2024-04-28T11:47:05.124Z Has data issue: false hasContentIssue false
  • English
  • Français

Levodopa-induced Dyskinesia in Parkinson’s Disease: Plausible Inflammatory and Oxidative Stress Biomarkers

Published online by Cambridge University Press:  20 January 2023

Swagata Sarkar Open the ORCID record for Swagata Sarkar [Opens in a new window] ,
Akash Roy Open the ORCID record for Akash Roy [Opens in a new window] ,
Supriyo Choudhury Open the ORCID record for Supriyo Choudhury [Opens in a new window] ,
Rebecca Banerjee ,
Sanjit Dey Open the ORCID record for Sanjit Dey [Opens in a new window]  and
Hrishikesh Kumar Open the ORCID record for Hrishikesh Kumar [Opens in a new window]
Swagata Sarkar
Affiliation:
Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, India Department of Physiology, University of Calcutta, Kolkata, India
Akash Roy
Affiliation:
Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, India Department of Physiology, University of Calcutta, Kolkata, India
Supriyo Choudhury
Affiliation:
Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, India
Rebecca Banerjee
Affiliation:
Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, India
Sanjit Dey
Affiliation:
Department of Physiology, University of Calcutta, Kolkata, India
Hrishikesh Kumar*
Affiliation:
Department of Neurology, Institute of Neurosciences Kolkata, Kolkata, India
*
Corresponding author: Dr Hrishikesh Kumar, Head, Department of Neurology, Institute of Neurosciences Kolkata, 185/1, A.J.C Bose Road, Kolkata- 700017, West Bengal, India. Email: rishi_medicine@yahoo.com
Get access Rights & Permissions [Opens in a new window]

Abstract:

Background:

Pathophysiology of levodopa-induced dyskinesia (LID) remains obscure. Increased dopamine metabolism due to prolonged levodopa treatment can exacerbate oxidative damage and neuroinflammatory pathology in Parkinson’s disease (PD). Association of novel peripheral markers with LID severity might provide insight into LID pathomechanisms.

Objective:

We aimed to study specific peripheral blood inflammatory-oxidative markers in LID patients and investigate their association with clinical severity of LID.

Method:

Motor, non-motor and cognitive changes in PD with and without LID compared to healthy-matched controls were identified. Within the same cohort, inflammatory marker (sLAG3, TOLLIP, NLRP3 and IL-1β) levels and antioxidant enzyme activities were determined by ELISA and spectrophotometric methods.

Results:

LID patients showed distinctly upregulated TOLLIP, IL-1β levels with significant diminution of antioxidant activity compared to controls. Significant negative association of cognitive markers with oxidative changes was also observed.

Conclusion:

To our understanding, this is the first study that indicates the involvement of toll-like receptor-mediated distinct and low-grade inflammatory activation in LID pathophysiology.

Résumé :

RÉSUMÉ :

Dyskinésie provoquée par la lévodopa : présence possible de biomarqueurs de stress oxydatif et d’inflammation.

Contexte :

On ne connaît pas très bien la physiopathologie de la dyskinésie provoquée par la lévodopa (DPL). Il se peut que l’augmentation du métabolisme de la dopamine due à un traitement prolongé par la lévodopa aggrave le stress oxydatif et le processus neuro-inflammatoire dans la maladie de Parkinson (MP). L’établissement d’une association de nouveaux marqueurs périphériques avec le degré de gravité de la DPL pourrait jeter un certain éclairage sur les mécanismes pathologiques de ce trouble d’exécution des mouvements.

Objectifs :

L’étude visait à détecter la présence de certains marqueurs de stress oxydatif et d’inflammation dans le sang périphérique, chez des patients présentant une DPL, et à examiner l’association de cette présence avec le degré de gravité clinique du trouble.

Méthode :

Une comparaison a été établie entre les changements moteurs, non moteurs et cognitifs notés chez des patients atteints de la MP, présentant ou non une DPL, et les résultats obtenus chez des témoins appariés, en bonne santé. Les taux de marqueurs d’inflammation (sLAG3, TOLLIP, NLRP3 et IL1-1β) et le degré d’activité enzymatique antioxydante ont été déterminés, dans la même cohorte, par la méthode ELISA et par spectrophotométrie.

Résultats :

Comparativement aux témoins, les patients atteints d’une DPL avaient une augmentation notable des taux de TOLLIP et d’IL1-1β, accompagnée d’une diminution importante de l’activité antioxydante. Une association négative significative a également été notée entre les marqueurs cognitifs et les changements oxydatifs.

Conclusion :

À notre connaissance, il s’agirait de la première étude dans laquelle les auteurs font état d’une activité inflammatoire de faible intensité, distincte, médiée par les récepteurs Toll (TLR) dans la physiopathologie de la DPL.

Keywords

sLAG-3TollipNLRP3InflammationOxidative markersLevodopa-induced dyskinesia
Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 51 , Issue 1 , January 2024 , pp. 104 - 109
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

SS and AR contributed equally to this research.

References

Albin, RL, Leventhal, DK. The missing, the short, and the long: levodopa responses and dopamine actions. Ann Neurol. 2017;82:4–19. DOI 10.1002/ana.24961.CrossRefGoogle Scholar
Eusebi, P, Romoli, M, Paoletti, FP, Tambasco, N, Calabresi, P, Parnetti, L. Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort. NPJ Parkinsons Dis. 2018;4:33. DOI 10.1038/s41531-018-0069-x.CrossRefGoogle ScholarPubMed
Zheng, Q, Liu, Z, Shen, H, Hu, X, Zhao, M. Protective effect of toll-interacting protein overexpression against paraquat-induced lung injury in mice and A549 cells through inhibiting oxidative stress, inflammation, and NF-κB signaling pathway. Respir Physiol Neurobiol. 2021;286:103600. DOI 10.1016/j.resp.2020.103600.CrossRefGoogle ScholarPubMed
Schroder, K, Tschopp, J. The inflammasomes. Cell. 2010;140:821–32. DOI 10.1016/j.cell.2010.01.040.CrossRefGoogle ScholarPubMed
Chatterjee, K, Roy, A, Banerjee, R, et al. Inflammasome and α-synuclein in Parkinson’s disease: a cross-sectional study. J Neuroimmunol. 2020;338:577089. DOI 10.1016/j.jneuroim.2019.577089.CrossRefGoogle ScholarPubMed
Roy, A, Choudhury, S, Banerjee, R, Basu, P, Kumar, H. Soluble LAG-3 and Toll-interacting protein: novel upstream neuro-inflammatory markers in Parkinson’s disease. Parkinsonism Relat Disord. 2021;91:121–3. DOI 10.1016/j.parkreldis.2021.09.019.CrossRefGoogle ScholarPubMed
Roy, A, Banerjee, R, Choudhury, S, et al. Novel inflammasome and oxidative modulators in Parkinson’s disease: a prospective study. Neurosci Lett. 2022;786:136768. DOI 10.1016/j.neulet.2022.136768.CrossRefGoogle ScholarPubMed
Roy, A, Mondal, B, Banerjee, R, et al. Do peripheral immune and neurotrophic markers correlate with motor severity of Parkinson’s disease? J Neuroimmunol. 2021;354:577545. DOI 10.1016/j.jneuroim.2021.577545.CrossRefGoogle ScholarPubMed
Hughes, AJ, Daniel, SE, Kilford, L, Lees, AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55:181–4. DOI 10.1136/jnnp.55.3.181.CrossRefGoogle ScholarPubMed
Guy, W. ECDEU assessment manual for psychopharmacology. US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976.Google Scholar
Lihala, S, Mitra, S, Neogy, S, et al. Dance movement therapy in rehabilitation of Parkinson’s disease - a feasibility study. J Bodyw Mov Ther. 2021;26:12–7. DOI 10.1016/j.jbmt.2020.06.032.CrossRefGoogle ScholarPubMed
Steer, RA, Rissmiller, DJ, Beck, AT. Use of the Beck Depression Inventory-II with depressed geriatric inpatients. Behav Res Ther. 2000;38:311–8. DOI 10.1016/s0005-7967(99)00068-6.CrossRefGoogle ScholarPubMed
Moron, MS, Depierre, JW, Mannervik, B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:67–78. DOI 10.1016/0304-4165(79)90289-7.CrossRefGoogle ScholarPubMed
Marklund, S, Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:469–74. DOI 10.1111/j.1432-1033.1974.tb03714.x.CrossRefGoogle Scholar
Yumoto, I II, Sawabe, H, Ueno, T, et al. Characterization of a facultatively psychrophilic bacterium, vibrio rumoiensis sp. nov., that exhibits high catalase activity. Appl Environ Microbiol. 1999;65:67–72. DOI 10.1128/aem.65.1.67-72.1999.CrossRefGoogle ScholarPubMed
Simuni, T, Stern, MB. Does levodopa accelerate Parkinson’s disease? Drugs Aging. 1999;14:399–408. DOI 10.2165/00002512-199914060-00001.CrossRefGoogle ScholarPubMed
Gabay, C, Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54. DOI 10.1056/nejm199902113400607.CrossRefGoogle ScholarPubMed
Luan, YY, Yao, YM. The clinical significance and potential role of C-reactive protein in chronic inflammatory and neurodegenerative diseases. Front Immunol. 2018;9:1302. DOI 10.3389/fimmu.2018.01302.CrossRefGoogle ScholarPubMed
Song, IU, Cho, HJ, Kim, JS, Park, IS, Lee, KS. Serum hs-CRP levels are increased in de Novo Parkinson’s disease independently from age of onset. Eur Neurol. 2014;72:285–9. DOI 10.1159/000363570.CrossRefGoogle ScholarPubMed
Hall, S, Janelidze, S, Surova, Y, Widner, H, Zetterberg, H, Hansson, O. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders. Sci Rep. 2018;8:13276. DOI 10.1038/s41598-018-31517-z.CrossRefGoogle ScholarPubMed
Jenner, P, Olanow, CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology. 1996;47:S161–70. DOI 10.1212/wnl.47.6_suppl_3.161s.CrossRefGoogle ScholarPubMed
Magistrelli, L, Ferrari, M, Furgiuele, A, et al. Polymorphisms of dopamine receptor genes and Parkinson’s disease: clinical relevance and future perspectives. Int J Mol Sci. 2021;22:3781. DOI 10.3390/ijms22073781.CrossRefGoogle ScholarPubMed
Mulas, G, Espa, E, Fenu, S, et al. Differential induction of dyskinesia and neuroinflammation by pulsatile versus continuous l-DOPA delivery in the 6-OHDA model of Parkinson’s disease. Exp Neurol. 2016;286:83–92. DOI 10.1016/j.expneurol.2016.09.013.CrossRefGoogle ScholarPubMed
Zhang, SF, Xie, CL, Lin, JY, Wang, MH, Wang, XJ, Liu, ZG. Lipoic acid alleviates LDOPAinduced dyskinesia in 6OHDA parkinsonian rats via antioxidative stress. Mol Med Rep. 2018;17:1118–24. DOI 10.3892/mmr.2017.7974.Google Scholar
Del-Bel, E, Bortolanza, M, Dos-Santos-Pereira, M, Bariotto, K, Raisman-Vozari, R. l-DOPA-induced dyskinesia in Parkinson’s disease: are neuroinflammation and astrocytes key elements? Synapse. 2016;70:479–500. DOI 10.1002/syn.21941.CrossRefGoogle ScholarPubMed
Bortolanza, M, Cavalcanti-Kiwiatkoski, R, Padovan-Neto, FE, et al. Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson’s disease. Neurobiol Dis. 2015;73:377–87. DOI 10.1016/j.nbd.2014.10.017.CrossRefGoogle Scholar
Bido, S, Marti, M, Morari, M. Amantadine attenuates levodopa-induced dyskinesia in mice and rats preventing the accompanying rise in nigral GABA levels. J Neurochem. 2011;118:1043–55. DOI 10.1111/j.1471-4159.2011.07376.x.CrossRefGoogle ScholarPubMed
Yan, A, Song, L, Zhang, Y, Wang, X, Liu, Z. Systemic inflammation increases the susceptibility to levodopa-induced dyskinesia in 6-OHDA lesioned rats by targeting the NR2B-medicated PKC/MEK/ERK pathway. Front Aging Neurosci. 2020;12:625166. DOI 10.3389/fnagi.2020.625166.CrossRefGoogle ScholarPubMed
Nicoletti, A, Mostile, G, Nicoletti, G, et al. Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson’s disease. J Neurol. 2016;263:888–94. DOI 10.1007/s00415-016-8075-6.CrossRefGoogle ScholarPubMed
van der Heeden, JF, Marinus, J, Martinez-Martin, P, Rodriguez-Blazquez, C, Geraedts, VJ, van Hilten, JJ. Postural instability and gait are associated with severity and prognosis of Parkinson disease. Neurology. 2016;86:2243–50. DOI 10.1212/wnl.0000000000002768.CrossRefGoogle ScholarPubMed
Supplementary material: File

Sarkar et al. supplementary material

Sarkar et al. supplementary material

Download Sarkar et al. supplementary material(File)
File 75.4 KB