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Propensity of Monocrotophos, an organophosphorus insecticide, to elicit and augment dopaminergic neuronal dysfunctions in animal models of Parkinson’s disease.

Shaheen, Jafri Ali (2014) Propensity of Monocrotophos, an organophosphorus insecticide, to elicit and augment dopaminergic neuronal dysfunctions in animal models of Parkinson’s disease. PhD thesis, University of Mysore.

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Abstract

(PD) in C. elegans and rodents (mice/rat). (c) delineate the mechanisms underlying the impact of MCP on the PD outcomes in C. elegans and rodents (mice/rat). C. elegans (N2 worms) exposed to MCP and MPTP showed dopaminergic features of Parkinson’s disease in terms of reduced locomotory rate, life span, dopamine content and AChE activity. MCP synergized the toxicity of MPTP in cotreated regime by further decreasing the locomotory rate, dopamine content, life span and glutathione ratios. Exposure of the mutant strain of C. elegans, cat-2 (with a TH ablation) and transgenic strain, BZ555 (with GFP tagged to the dopaminergic neurons) to MCP, MPTP and co-treatment regime further established the propensity of MCP to elicit and augment dopaminergic neuronal dysfunctions in C. elegans as measured in terms of locomotion and regionally specific degeneration of dopaminergic neurons. Rats treated with MCP for 7d and 30d showed significant reduction in grip strength. Rotenone (ROT), a model PD-toxin also induced a significant decrease in the grip strength in rats. Rats co-treated with MCP along with ROT showed significant decrease in the grip strength compared to control after 15d. MCP treated rats exhibited a significant decrease in the dopamine content in striatum compared to control after 7 and 30d. However, ROT treated rats did not show decrease in the dopamine content in striatum after 15d. Rats co-treated with MCP along with ROT showed also did not show decrease in the dopamine content after 15d. Our results demonstrate that ROT at the tested doses and duration failed to elicit significant parkinsonism in rat, other than decreasing grip strength. However, interestingly, MCP per se elicited features of parkinsonism in rat – decreased grip strength, decreased dopamine content and AChE activity in striatum. MCP treatment for 7d and 30d induced a reduction in grip strength in mice similar to that elicited by MPTP (another model PD toxin) which was further decreased by co-treatment with MPTP + MCP. Dopamine levels were decreased after 30d of MCP treatment and 7d of co-treatment with MPTP. MCP treated mice showed comparable degree neuronal degeneration with hypertrophy of neurons in striatum similar to mice co-treated with MPTP. MPTP treatment induced a significant decrease in the tyrosine hydroxylase positive (TH+) cells in the striatum, which was further decreased upon treatment with MCP. MCP+MPTP induced oxidative stress and decreased markers of mitochondrial functions. Our results thus show that exposure to low levels of MCP is likely to interfere with the functional capacity of the nigrostriatal tract and hence can contribute towards developing PD. Overall, our findings provide substantial evidence to the hypothesis that the dopaminergic system of C. elegans can be exploited to provide mechanistic insights and interactive outcomes of exposure to neurotoxic insecticides. Further, similar responses obtained with MCP exposure in the rat model confirmed the potential of MCP to induce PD-like symptoms. More importantly, our comprehensive findings in the mice model lends further credence on the propensity of MCP to elicit as well augment striatal/ dopaminergic neurodegeneration.

Item Type: Thesis (PhD)
Uncontrolled Keywords: pesticide exposure, Parkinson’s disease, neurotoxicity, Caenorhabditis elegans
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 26 Pesticide Chemistry
600 Technology > 01 Medical sciences > 17 Toxicology
Divisions: Food Protectants and Infestation Control
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 19 Mar 2015 11:02
Last Modified: 19 Mar 2015 11:02
URI: http://ir.cftri.com/id/eprint/11762

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