Category: Parkinson's Disease: Pathophysiology
Objective: The purpose of the study is to establish an all-around model for Parkinson’s disease using Drosophila melanogaster, the fruit-fly in order to understand behavioral index and pathophysiology related to neuronal/mitochondrial/redox function.
Background: The lack of a complete model which can be used to study all the aspects of a neurological disorder that includes biochemical changes in the organelles (mitochondria, microsome), neurons (dopaminergic neurons) as well as behavioral index is a concern for drug discovery. Our effort is to develop a quick study model to understand the pathophysiology of PD using Drosophila larvae by exposing to PD-toxins like rotenone (and paraquat) along with buthionine sulfoximine (BSO) to induce glutathione (GSH)-depletion.
Method: Second instar larvae of Drosophila were exposed to rotenone(0.1mM) and 1mM-BSO over 24 hours. Additionally, rotenone+BSO exposed larvae were coexposed with phyto-constituents isolated from Selaginella delicatula. The larvae were monitored for behavioural index using crawling assay, exploratory assay as well as locomotor speed of the larvae on a customized open field agar-plate(10X10cm). Terminally the whole body homogenates and neuronal preparations from the larvae were subjected to biochemical analysis of mitochondrial function, dopamine as well as reduced glutathione (GSH)/redox status.
Results: As anticipated rotenone induced crawling disabilities and reduction in speed of the larvae, while the homogenates revealed reduction in dopamine levels. And BSO significantly reduced GSH levels among homogenates. The combination of rotenone+BSO further damaged the redox status and mitochondrial membrane potential (and complex I activity) along with GSH levels. Interestingly, the Selaginella phyto-constituents significantly normalized the glutathione levels as well as ameliorating the behavioral and biochemical changes (including dopamine levels) among Drosophila larvae. Additionally catalase/superoxide dismutase activities also were ameliorated by the phytoconstituents in the treated larvae.
Conclusion: These findings are preliminary, however have been tested using different antioxidants and drug candidates with promising results. We propose to further elucidate the possibilities of this model to study the pathophysiology of PD and possible therapeutic interventions.
To cite this abstract in AMA style:G. Chandran, R. D'Silva, M. Muralidhara. Use of insect model to study Parkinson’s disease pathophysiology by inducing GSH-depletion and behavioral deficits among larvae: Evidences of ameliorative properties of phytoconstituents [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/use-of-insect-model-to-study-parkinsons-disease-pathophysiology-by-inducing-gsh-depletion-and-behavioral-deficits-among-larvae-evidences-of-ameliorative-properties-of-phytoconstituents/. Accessed September 22, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/use-of-insect-model-to-study-parkinsons-disease-pathophysiology-by-inducing-gsh-depletion-and-behavioral-deficits-among-larvae-evidences-of-ameliorative-properties-of-phytoconstituents/