Metabolomic Analysis Provides Insights on Paraquat-Induced Parkinson-Like Symptoms in Drosophila melanogaster

• Published in: Molecular neurobiology 2016-01, Vol.53 (1), p.254-269
• Main Authors: Shukla, Arvind Kumar, Ratnasekhar, Ch, Pragya, Prakash, Chaouhan, Hitesh Singh, Patel, Devendra Kumar, Chowdhuri, Debapratim Kar, Mudiam, Mohana Krishna Reddy
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - metabolism; Brain - pathology; Cell Biology; Drosophila melanogaster; Drosophila melanogaster - drug effects; Drosophila melanogaster - metabolism; Gas Chromatography-Mass Spectrometry; Metabolic Networks and Pathways - drug effects; Metabolites; Metabolome; Metabolomics - methods; Motor Activity - drug effects; Nerve Degeneration - chemically induced; Nerve Degeneration - pathology; Neurobiology; Neurodegeneration; Neurology; Neurosciences; Oxidative stress; Oxidative Stress - drug effects; Paraquat - toxicity; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson Disease - physiopathology; Parkinson's disease; Principal Component Analysis; Reproducibility of Results
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-014-9003-3

Paraquat (PQ) exposure causes degeneration of the dopaminergic neurons in an exposed organism while altered metabolism has a role in various neurodegenerative disorders. Therefore, the study presented here was conceived to depict the role of altered metabolism in PQ-induced Parkinson-like symptoms and to explore Drosophila as a potential model organism for such studies. Metabolic profile was generated in control and in flies that were fed PQ (5, 10, and 20 mM) in the diet for 12 and 24 h concurrent with assessment of indices of oxidative stress, dopaminergic neurodegeneration, and behavioral alteration. PQ was found to significantly alter 24 metabolites belonging to different biological pathways along with significant alterations in the above indices. In addition, PQ attenuated brain dopamine content in the exposed organism. The study demonstrates that PQ-induced alteration in the metabolites leads to oxidative stress and neurodegeneration in the exposed organism along with movement disorder, a phenotype typical of Parkinson-like symptoms. The study is relevant in the context of Drosophila and humans because similar alteration in the metabolic pathways has been observed in both PQ-exposed Drosophila and in postmortem samples of patients with Parkinsonism. Furthermore, this study provides advocacy towards the applicability of Drosophila as an alternate model organism for pre-screening of environmental chemicals for their neurodegenerative potential with altered metabolism.