[
International Worm Meeting,
2013]
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting about 1 - 2% of the population over the age of 65. PD encompasses a spectrum of core clinical features such as rigidity, bradykinesia, tremor at rest and postural instability. However, PD is a heterogeneous disorder, as many patients also develop cognitive dysfunctions, including anxiety, depression and dementia or abnormalities in olfactory and visual perception. Pathologically, PD is characterized by the specific and massive loss of dopamine (DA) containing neurons in the Substantia Nigra pars compacta and aggregation of protein alpha-Synuclein levels. Poly unsaturated fatty acid (PUFA) are highly abundant in the brain and omega-3 and omega-6 PUFA are essential structural components of the cell membrane phospholipids. Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. In the present study, the chemically induced PD symptoms in transgenic Caenorhabditis elegans UA44 (baln11;Pdat-1::Pdat-1::GFP) exposed to various concentration of 6-Hydroxydopamine (6-OHDA) by exposing from the egg stage to adult larva with and with out supplementation of PUFA Linoleic acid (LA) along with food source. The results were confirmed by various parameters, the decreased locomotion being normalized to like control by counting number of body bends (29 and 42% decrease in locomotion in 5 and 25mM 6-OHDA and 20% protection by LA against 6-OHDA), body thrashing and cognition enhancement by PUFA (LA) supplemented groups are well evidenced. The main markers of PD symptoms alpha Synuclein accumulation and degeneration of dopamine neuron were similarly reduced, as evidenced by fluorescence intensity and microscopic analysis. The mitochondrial enzymes decreased were measured such as Succinate dehydrogenase, complex I and IV, total thiols and cytochrome c activity. In conclusion, the nematode model C. elegans with its simple nervous system and GFP tagged dopaminergic neuron offer an valuable tool for studying the pathogenesis of Parkinson disease and evaluate the anti-Parkinsonian effects of PUFA molecules.
[
International Worm Meeting,
2009]
Synthetic pyrethroids (SP), are derived from pyrethrins are being used as insecticides and potently toxic to insect species,offer the advantage of low mammalian toxicity. Extensive use of SP raises concerns of toxicity to non-target organisms. SP produce symptoms viz: behavioral changes, tremors and hyperexcitation in animals. SP mainly act on nervous system by delaying closing of voltage dependent sodium channels. Their secondary effects involve oxidative stress leading to macromolecular damages. Reports are available on the toxicological effects of SP in rats, mice, Drosophila melanogaster and other model organisms. There is paucity of data on effects of SP on Caenorhabditis elegans, which is rapidly gaining popularity as a model for toxicological evaluations. In this study, we investigated the effects of cypermethrin (CYP) a potent type-P SP on physiological endpoints (brood size, egg laying and feeding), indices of neurotoxicity (acetylcholinesterase and acetyl choline) and markers of oxidative imbalances in C. elegans. Exposure of worms to maximum soluble concentration of CYP (20mM) failed to induce mortality in worms. Hence experiments were conducted with sublethal concentrations of CYP (1, 5, and 15mM). Exposure of worms to the above concentrations of CYP for 4h was associated with concentration-dependent decrease in brood size (18-54%), feeding rate (28-54%) and egg laying (55-67%) increase in the activities of acetylcholinesterase (9-59%) & carboxylesterase (26-86%) & acetylcholine (25-47%) levels. Alterations in oxidative balance as a consequence of CYP treatment were evident as elevated levels of ROS (20-56%). Exposure to CYP initiated at the egg stage and continued for 24, 36, 48 and 72h produced qualitative changes in fatty acid profile of worms and decrease in body length. Further studies were conducted with a-tocopherol to explore the possibility of ameliorating oxidative imbalances caused by CYP. Co-treatment of worms with a-tocopherol abrogated CYP-induced oxidative imbalance as reflected by lower levels of ROS (30 vs 46%) and protein carbonyls (14 vs 28%) compared to worms exposed to CYP alone. a-tocopherol also protected worms from CYP-induced decrease in reduced glutathione and alterations in the activities of antioxidant enzymes. In conclusion, our data suggest that at sublethal concentration CYP induces neurophysiolical alterations and oxidative stress, the latter of which was amenable for amelioration by a-tocopherol. Hence C. elegans could be reliably employed for understanding the role of oxidative stress in toxic outcomes of xenobiotics.