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

Abstract

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.

Correction to: Paraquat-Induced Movement Disorder in Relation to Oxidative Stress-Mediated Neurodegeneration in the Brain of Drosophila melanogaster

“…In some of the earlier studies, acute exposure to PQ led to increased activity of SOD [17,35], whereas, others have reported reduced activity of SOD at higher dose [37,38]. In our study, flies exposed to multiple-dose of PQ showed a markedly decreased activity of both Cu/Zn-SOD and mitochondrial Mn-SOD in contrast to the acute exposure.…”

Neuroprotective effects of PACAP against paraquat-induced oxidative stress in the Drosophila central nervous system

“…Here we examined the effect of PACAP in a widely used sporadic PD model induced by PQ exposure in Drosophila (34,37,39,87). Since the fly orthologue of PACAP has not yet been identified with confidence (41), we used the amino acid sequence of PACAP-38, which is identical in all mammals, and because PACAP could not cross the intestinal barrier and remain intact, we directly applied the neuropeptide to the exposed VNC of decapitated Drosophila before PQ exposure, using a previously established procedure (39).…”

A Neuron-Glial Trans-Signaling Cascade Mediates LRRK2-Induced Neurodegeneration

“…For Gal80 ts experiments, 5-day-old female flies were shifted to 29°C. For paraquat experiments, 5 day-old-female flies were shifted to 2 mM paraquat in a sucrose- (5%) and agar-containing (1.3%) medium ( Shukla et al, 2014 ). For Gene-Switch experiments, 5-day-old flies were transferred to standard or paraquat media and were supplemented with 200 μM RU486.…”