Therapeutic Intervention of Curcumin in Rotenone Mediated Dopaminergic Neurodegeneration: Insights from Drosophila Model of Parkinson’s disease

Title : Therapeutic Intervention of Curcumin in Rotenone Mediated Dopaminergic Neurodegeneration: Insights from Drosophila Model of Parkinson’s disease

Abstract:

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 multiple animal models. Drosophila is susceptible to rotenone in dose-time dependent manner. Rotenone also induces locomotory defects in Drosophila. Curcumin rescues mobility defects associated with rotenone exposure in Drosophila model during health span whereas it fails to rescue the mobility defects in early and late 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 is the characteristic pathogenic feature of PD. Study of dopaminergic neurons in whole mount fly brain using in situ immunostaining technique reveals that rotenone causes neuronal dysfunction. Albeit, there is no significant difference in the number of dopaminergic neurons, there is significant decrease (~40-50%) in the pixel intensity under diseased condition which is significantly altered upon co-feeding with curcumin, suggesting the diminished levels of rate limiting enzyme Tyrosine hydroxylase and subsequent levels of dopamine. Further, quantification of the levels of brain specific dopamine (DA) and its metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) using HPLC shows that level of dopamine is significantly reduced (~30-40%) under diseased conditions which could be rescued upon co-feeding with curcumin in young flies but not in old aged flies. 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

Biography:

Mr. Mohamad Ayajuddin studied Biosciences at Barkatullah University, India and graduated as M. Phil. in 2009. He joined oceanography research group of Dr Z.A. Ansari at National Institute of Oceanography (NIO), India. Later, he joined Dr Sarat’s group at Nagaland University, India and started working in the field of neurobiology for his doctoral programme. He is working on the rotenone mediated Drosophila model of Parkinson’s disease to understand the efficacy of certain phytochemicals at different life stages specific fashion. He has published 7 research articles, 4 book chapters and co-edited a book. He has also attended many national and international conferences.