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Elicitation of Dopaminergic Features of Parkinson’s Disease in C. elegans by Monocrotophos, an Organophosphorous Insecticide

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Relation http://ir.cftri.com/12283/
http://dx.doi.org/10.2174/1871527311211080008
 
Title Elicitation of Dopaminergic Features of Parkinson’s Disease in C. elegans by Monocrotophos, an Organophosphorous Insecticide
 
Creator Shaheen, Jafri Ali
Rajini, P. S.
 
Subject 26 Pesticide Chemistry
09 Human Physiology
 
Description Positive correlations have been suggested between usage of pesticides and the incidence of Parkinson's disease (PD) through epidemiological as well as few experimental evidences. Organophosphorus insecticides (OPI) , which are extensively used in agricultural and household insect control, have been the subject of increasing concern in the past decades due to their neurotoxic potential. However, very few studies have demonstrated the potentials of OPI to induce features of PD in model organisms. In the present study, Caenorhabditis elegans was selected as the model organism to evaluate the potential of monocrotophos (MCP) , an OPI, to elicit dopaminergic features of Parkinson's disease in terms of dopamine content, basic movement and integrity of dopaminergic neuronsalong with its effect on acetylcholinesterase (AChE) activity and life span. All the responses elicited by MCP were compared with that elicited by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in both N2 and BZ555 worms. N2 worms were exposed to varying concentrations of MCP (50, 100 and 200µM) or MPTP (200, 300 and 400µM) for 48 hours and locomotory rate, as measured by the number of body bends made in 20 seconds, was enumerated. Worms subjected to the same dose paradigms were also analyzed for the dopamine content by HPLC. The results indicated a significant reduction in the dopamine levels in the worms that were treated with MCP/MPTP and this correlated with the changes in locomotion compared to untreated worms. Worms treated with MCPalso exhibited significant reduction in AChE activity. Both MPTP and MCP caused a marked reduction in life span in the worms. Transgenic worms (BZ555, which has GFP tagged to its 8 dopaminergic neurons) exposed to MCP and MPTP at the above concentrations showed a dose-dependent reduction in the number of green pixels in CEP and ADE neurons which also correlated with the neurodegeneration as visualized by decreased fluorescence in photomicrographs. Taken together, our data demonstrate that low levels of MCP elicitsdopaminergic features of PD in C. elegans.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/12283/1/SJA-CNSND_DT.pdf
Shaheen, Jafri Ali and Rajini, P. S. (2012) Elicitation of Dopaminergic Features of Parkinson’s Disease in C. elegans by Monocrotophos, an Organophosphorous Insecticide. CNS and Neurological Disorders Drug Targets, 11. pp. 993-1000.