Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats

Cicchetti, Francesca; Lapointe, Nicolas P.; Roberge-Tremblay, Antoine; Saint-Pierre, Martine; Jimenez, Lincoln; Ficke, Brooks W.; Gross, Robert E.

doi:10.1016/j.nbd.2005.03.018

Cited by 158 publications

(132 citation statements)

References 44 publications

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“…A similar argument can be made in a rat model in which paraquat is injected weekly for 24 wks but only 30% reduction in dopamine is detected (Ossowska et al 2005). Given that paraquat is known to cause pulmonary toxicity (Clark et al 1966;Smith and Heath 1976;Cicchetti et al 2005;Saint-Pierre et al 2006), which could affect motor performance, it may be necessary to assess whether L-dopa can alleviate motor deficits induced by paraquat. As discussed, this strategy has been used in the MPTP and 6-OHDA animal models to confirm that the observed motor deficit is linked to the damage of the nigrostriatal pathway.…”

Section: Paraquatmentioning

confidence: 77%

“…The effects of paraquat on nigral dopaminergic neurons appear to be specific as g-amino butyric acid (GABA) neurons in the nigral and striatal regions, glutamate neurons in the hippocampus, and dopaminergic neurons in the ventral tegmental area are not affected (Thiruchelvam et al 2000b;McCormack et al 2002). However, the damage induced by paraquat in dopaminergic cell bodies and terminals has not been consistently observed (Thiruchelvam et al 2000b;Cicchetti et al 2005). Furthermore, even in studies in which a loss in nigral dopaminergic neurons is detected, paraquat does not have an effect on striatal dopamine levels (Thiruchelvam et al 2000b;McCormack et al 2002).…”

Section: Paraquatmentioning

confidence: 99%

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A Guide to Neurotoxic Animal Models of Parkinson's Disease

Tieu¹

2011

Cold Spring Harbor Perspectives in Medicine

398

299

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Parkinson's disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway.

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Section: Paraquatmentioning

confidence: 77%

Section: Paraquatmentioning

confidence: 99%

A Guide to Neurotoxic Animal Models of Parkinson's Disease

Tieu¹

2011

Cold Spring Harbor Perspectives in Medicine

398

299

View full text Add to dashboard Cite

show abstract

“…For example, a significant decrease in complex I activity of the mitochondrial respiratory chain, accompanied by reduced levels of coenzyme Q 10 (CoQ 10 ), is found in the brain and platelets of PD patients (Hargreaves et al, 2008;Shults et al, 1998Shults et al, , 1999. In experimental settings, several chemicals (i.e., MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine], paraquat, and rotenone) that inactivate complex I of the oxidative phosphorylation pathway also induce degeneration of dopaminergic neurotransmission in rodents (Cannon et al, 2009;Cicchetti et al, 2005;Jackson-Lewis and Przedborski, 2007;McCarthy et al, 2004). All this leads to the conclusions that the excessive reactive oxygen species (ROS) burden, some of it generated by dysfunctional mitochondria, and the inability of dopamine (DA) neurons to neutralize them are at the center of PD pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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“…In this context, the role of pesticides as potential environmental risk factors for PD has long been suspected and recurrent through multiple epidemiological meta-analyses, though the specific causative agents and the mechanisms underlying the disease are not fully understood (Priyadarshi et al, 2000;Franco et al, 2010;Ntzani et al, 2013;Baltazar et al, 2014). For this reason, PD and parkinsonian disorders in general is of high interest for the pesticides risk assessment and several experimental models have been proposed (Drechsel and Patel, 2008;Cicchetti et al, 2009;Moretto and Colosio, 2011;Baltazar et al, 2014). However, the linkage of a complex, multihit and unique human disease with experimental toxicological studies is still representing an important challenge for risk assessment.…”

Section: Complex Molecular Landscape Of Pd and Parkinsonian Disordersmentioning

confidence: 99%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats

Cited by 158 publications

References 44 publications

A Guide to Neurotoxic Animal Models of Parkinson's Disease

A Guide to Neurotoxic Animal Models of Parkinson's Disease

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

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