A highly reproducible rotenone model of Parkinson's disease

Cannon, Jason R.; Tapias, Vı́ctor; Na, Hye Mee; Honick, Anthony S.; Drolet, Robert E.; Greenamyre, J. Timothy

doi:10.1016/j.nbd.2009.01.016

Cited by 653 publications

(533 citation statements)

References 37 publications

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“…For detection of antigen signal, sections were washed thrice with PBS and incubated in avidin-biotin complex (ABC) (Millipore) solution. After washing in PBS, the sections were developed using diaminobenzidine (DAB) (Millipore, #DAB500) to visualize the brown color precipitate at the antigen sites (Cannon et al, 2009).…”

Section: Neurobehavioral Analysismentioning

confidence: 99%

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Ahmed¹,

Shaikh²,

Baloch³

et al. 2018

Int. J. Morphol.

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SUMMARY:Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.

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Section: Neurobehavioral Analysismentioning

confidence: 99%

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Ahmed¹,

Shaikh²,

Baloch³

et al. 2018

Int. J. Morphol.

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“…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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“…For in vivo detection of ROS at the steady-state concentration, we imaged mice (CD-1, male, n 5 6, 12 weeks old, 50 6 6 g body weight) treated with rotenone solutions (an IP bolus injection, 20 mg/kg body weight) that were prepared based on previous reports. 24,25 In brief, rotenone dissolved in chloroform (>99%, Sigma-Aldrich) was mixed with 4% of carboxymethylcellulose (Sigma-Aldrich) to render a final concentration of 1.25 mg/mL. MRI of mouse brains was performed at baseline and 1.5 hours post-rotenone injection.…”

mentioning

confidence: 99%

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

Tain

Scotti

et al. 2017

Magnetic Resonance Imaging

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Purpose: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). Materials and Methods: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T 1 and T 2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H 2 O 2 ) were used to evaluate the effect of produced ROS in T 1 and T 2 for up to 4 hours. pH and temperature changes due to H 2 O 2 treatment in egg white were also monitored. The influences from H 2 O 2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T 1 in H 2 O 2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T 1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n 5 6). Results: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <18C, respectively). T 1 relaxation time in the H 2 O 2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T 2 (<10%). In the H 2 O 2 -treated BSA solution that produce no ROS, there was a small change in T 1 due to H 2 O 2 itself (61%), although a significant T 2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T 1 (13 6 1%) and T 2 (1 6 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T 1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 3 10 7 vs. 0.9 s 21 ÁmM 21 ). Finally, significantly reduced T 1 was observed in rotenone-treated mouse brain (5.1 6 2.5%, P < 0.05). Conclusion: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. Level of Evidence: 2 Technical Efficacy Stage: 2 J. MAGN. RESON. IMAGING 2018;47:222-229. R eactive oxygen species (ROS), including singlet oxygen, and hydroxyl radical (ÁOH), have long been subjects of study due to their central role in cell signaling, the aging process, and in the pathogenesis of a variety of diseases such as cardiovascular diseases, diabetes, cancer, Alzheimer's, and Parkinson's diseases. 1-5 ROS can be divided into radical species (eg, ÁOH) and nonradical species (eg, H 2 O 2 ). They are mainly produced by several different enzyme systems (eg, cytosolic enzyme) and by the mitochondrial complex I and III. 6 They can react readily with any surrounding tissue component (eg, lipids, proteins, and DNA) 2 and can initiate complicated chain processes with high biological impact (eg, Haber-Weiss or Fenton reactions). 7 The high reactivity and short lifetime of radical ROS make them very challenging to detect. For example, the lifetime...

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A highly reproducible rotenone model of Parkinson's disease

Cited by 653 publications

References 37 publications

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

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

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

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