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

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Title Propensity of
Monocrotophos, an organophosphorus insecticide, to elicit and
augment dopaminergic neuronal dysfunctions in animal models of
Parkinson’s disease.
 
Creator Shaheen, Jafri Ali
 
Subject 26 Pesticide Chemistry
17 Toxicology
 
Description (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.
 
Contributor Rajini, P. S.
 
Date 2014
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Language en
 
Rights —
 
Identifier http://ir.cftri.com/11762/1/Shaeen.pdf
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.