Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To understand the efficacy of curcumin in rotenone induced Drosophila model of Parkinson’s disease.
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over age 50. Exposure to environmental toxins has been found to be a risk factor for sporadic PD. Herbicide rotenone has been shown to cause Parkinsonian symptoms in Drosophila models.
Results: Drosophila is susceptible to rotenone in dose-time dependent manner. Rotenone also induces locomotory defects in Drosophila. Curcumin rescues mobility defects (climbing phenotype) associated with rotenone exposure in Drosophila model during health span whereas it fails to rescue the mobility defects in late health span and transition stage illustrating the limitations of curcumin in mitigating the pathology associated with rotenone mediated neurodegeneration in Drosophila model of PD. In humans, death of dopaminergic neurons in the substantia nigra (SN) is the characteristic pathogenic feature of Parkinson’s disease. Study of dopaminergic neurons in whole mount fly brain using in situ hybridization technique reveals that rotenone causes neuronal dysfunction. Albeit, there is no significant difference in the number of dopaminergic neurons, there is significant decrease of about 40-50% in the pixel intensity under diseased condition which is significantly altered upon cofeeding with curcumin in young flies. Further, upon quantification of the levels of brain specific dopamine (DA) and its metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) shows that level of dopamine is significantly reduced to 30-40% under diseased conditions which could be rescued upon co-feeding with curcumin in young flies but not in old aged flies while the level of metabolites varies in different stages of the life span of Drosophila.
Conclusion: These results show that curcumin mitigates the rotenone mediated dopaminergic degeneration only in young flies. The results also illustrate the limitation of curcumin in dopaminergic neuroprotection and probable targets of curcumin for neuroprotection only during health phase of adult life span of Drosophila.
References: Ayajuddin M, Das A, Phom L, Modi P, Koza Z, Chaurasia R, Thepa A, Jamir N, Singh PR, Sentinungla, Lal P and Yenisetti SC. 2018. Parkinson’s Disease: Insights from Drosophila Model In: Drosophila melanogaster – Model for Recent Advances in Genetics and Therapeutics. Farzana Khan Perveen (Ed). In-tech Croatia, European Union. pp 157-192. Coulom H and Birman S. 2004. Chronic Exposure to Rotenone Models Sporadic Parkinson’s Disease in Drosophila melanogaster The Journal of Neuroscience. 24(48):10993–10998
To cite this abstract in AMA style:M. Ayajuddin, SC. Yenisetti. Limitations of Curcumin as a Therapeutic Agent in Rotenone Induced Dopaminergic Neurodegeneration: Insights from Drosophila Model of Parkinson’s Disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/limitations-of-curcumin-as-a-therapeutic-agent-in-rotenone-induced-dopaminergic-neurodegeneration-insights-from-drosophila-model-of-parkinsons-disease/. Accessed November 29, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/limitations-of-curcumin-as-a-therapeutic-agent-in-rotenone-induced-dopaminergic-neurodegeneration-insights-from-drosophila-model-of-parkinsons-disease/