Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats

Kuter, Katarzyna; Śmiałowska, Maria; Wierońska, Joanna M.; Zieba, Barbara A.; Wardas, Jadwiga; Pietraszek, M.; Nowak, Przemysław; Biedka, I.; Roczniak, Wojciech; Konieczny, Jolanta; Wolfarth, S; Ossowska, Krystyna

doi:10.1016/j.brainres.2007.04.018

Cited by 70 publications

(46 citation statements)

References 59 publications

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“…Therefore, the mechanism of paraquat neurotoxicity is most likely mediated via oxidative stress [12]. Interestingly, paraquat has been shown to specifically damage dopaminergic neuronal cells in in vivo studies with Drosophila melanogaster [13], rats [14] and mice [15,16]. These data clearly demonstrated that dopaminergic neurons are responsible for the movement function in flies and mammals and that either genetically or environmentally induced damage of those neurons resulted in motor dysfunction.…”

Section: Introductionmentioning

confidence: 91%

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

2009

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Parkinson's disease (PD) is a common progressive neurodegenerative disorder, for which at present no causal treatment is available. On the understanding that the causes of PD are mainly oxidative stress and mitochondrial dysfunction, antioxidants and other drugs are expected to be used. In the present study, we demonstrated for the first time that pure polyphenols such as gallic acid, ferulic acid, caffeic acid, coumaric acid, propyl gallate, epicatechin, epigallocatechin, and epigallocatechin gallate protect, rescue and, most importantly, restore the impaired movement activity (i.e., climbing capability) induced by paraquat in Drosophila melanogaster, a valid model of PD. We also showed for the first time that high concentrations of iron (e.g. 15 mM FeSO(4)) are able to diminish fly survival and movement to a similar extent as (20 mM) paraquat treatment. Moreover, paraquat and iron synergistically affect both survival and locomotor function. Remarkably, propyl gallate and epigallocatechin gallate protected and maintained movement abilities in flies co-treated with paraquat and iron. Our findings indicate that pure polyphenols might be potent neuroprotective agents for the treatment of PD against stressful stimuli.

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Section: Introductionmentioning

confidence: 91%

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

2009

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“…In mice a single paraquat injection causes a priming effect, leading to significant nigrostriatal cell loss after the second injection (Purisai et al, 2007). In rats, however, at least 5 injections of paraquat at the same dose (10 mg/kg) are necessary to induce cell death (Cicchetti et al, 2005;Kuter et al, 2007). Therefore the lack of potentiation after paraquat administration seen in older rats is unlikely to be due to differences in the priming effect of the first injection in our rat model, but may due to the longer time period between the two insults, as suggested for other factors that modify the effects of TBI (Bramlett et al, 1999;Jenkins et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

Hutson

Lazo

Mortazavi

et al. 2011

Journal of Neurotrauma

118

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. In an acute study, rats received moderate TBI by lateral fluid percussion (LFP) injury, were injected with saline or paraquat (10 mg/kg IP) 3 and 6 days after LFP, were sacrificed 5 days later, and their brains processed for immunohistochemistry. TBI alone increased microglial activation in the substantia nigra, and caused a 15% loss of dopaminergic neurons ipsilaterally. Paraquat increased the TBI effect, causing a 30% bilateral loss of dopaminergic neurons, reduced striatal tyrosine hydroxylase (TH) immunoreactivity more than TBI alone, and induced alpha-synuclein accumulation in the substantia nigra pars compacta. In a long-term study, rats received moderate LFP, were injected with saline or paraquat at 21 and 22 weeks post-injury, and were sacrificed 4 weeks later. At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk.

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“…Thus, whereas MPP+ and rotenone directly inhibit Complex I function, PQ indirectly disrupts mitochondrial function via intra-mitochondrial ROS formation through Complex I interactions with PQ. Various investigators have demonstrated small but significant losses of SN DA neurons with PQ [12,36,69,85,93] and up-regulation and aggregation of alpha-synuclein [29,83]. However, studies have yet to demonstrate progressive DA cell loss or motor deficits.…”

Section: Pd Models: Acute or Chronic Delivery Of Neurotoxicantsmentioning

confidence: 99%

Animal models of Parkinson’s disease progression

Sonsalla²,

2008

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Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. This disease occurs both sporadically and through inheritance of single genes, although the familial types are rare. Over the past decade or so, experimental and clinical data suggest that PD could be a multifactorial, neurodegenerative disease that involves strong interactions between the environment and genetic predisposition. Our understanding of the pathophysiology and motor deficits of the disease relies heavily on fundamental research on animal models and the last few years have seen an explosion of toxin-, inflammation-induced and genetically manipulated models. The insight gained from the use of such models has strongly advanced our understanding of the progression and stages of the disease. The models have also aided the development of novel therapies to improve symptomatic management, and they are critical for the development of neuroprotective strategies. This review critically evaluates these in vivo models and the roles they play in mimicking the progression of PD.

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Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats

Cited by 70 publications

References 59 publications

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

The Effects of Polyphenols on Survival and Locomotor Activity in Drosophila melanogaster Exposed to Iron and Paraquat

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

Animal models of Parkinson’s disease progression

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