Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson’s disease evaluated with multimodal MRI

Perlbarg, Vincent; Lambert, Justine; Butler, Benjamin J.; Felfli, Mehdi; Valabrègue, Romain; Privat, Anne-Laure; Lehericy, Stéphane; Petiet, Alexandra

doi:10.1371/journal.pone.0202597

Cited by 33 publications

(27 citation statements)

References 40 publications

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“…The 6-OHDA model is a classic and widely used neurotoxin rodent model of PD. The bilateral administration of 6-OHDA into the striatum induces retrograde neuronal cell death of the tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) mimicking Parkinson-like pathology [ 56 , 57 ]. Here, the animals were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) intraperitoneally and placed in the stereotactic device (EFF 331-Insight™, Ribeirão Preto, São Paulo, Brazil) ( Figure 1 A).…”

Section: Methodsmentioning

confidence: 99%

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

et al. 2020

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Patients with Parkinson’s disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (p = 1.47 × 10−19), SDNN (p = 3.42 × 10−10) and RMSSD (p = 8.2 × 10−6) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (p = 5.66 × 10−15) and reduced striatal fiber degeneration (p = 7.4 × 10−5) in 6-OHDA-injured rats, which also showed significant weight gain (p = 1.07 × 10−5) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.

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Section: Methodsmentioning

confidence: 99%

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

et al. 2020

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“…The neurotoxin 6-OHDA is one of the proposed for modeling PD research in animal models [ 74 ]. The administration of 6-OHDA is variably unilateral into the nigrostriatal pathway to produce neurodegeneration, and various 6-OHDA animal models have been conventional for the PD investigations [ 75 , 76 ]. 6-OHDA is a lethal toxin that mainly damages peripheral and central nervous systems [ 77 ].…”

Section: Neurotoxins Used To Induce Pd In Vivo Modelsmentioning

confidence: 99%

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Prasad

Hung

2020

Antioxidants

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Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

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“…A voxel-based analysis of a 7 T DTI study in marmosets before and after MPTP administration revealed increased diffusivity in the bilateral nigrostriatal pathway, validated by ex-vivo microscopic tractographic images, which showed loss of fiber structures in the MPTP-treated brain (Hikishima et al, 2015 ) and a longitudinal combined morphometric and DTI study in cynomolgus monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas (Jeong et al, 2018 ). Further DTI studies (within multimodal imaging protocols) demonstrated significantly altered diffusivity parameters (MD, AD, RD) in the nigrostriatal tract (in correlation with MPTP dose), but not in the substantia nigra or striatum, in the macaque nemestrina after application of MPTP (Shimony et al, 2018 ) and increased FA in the ipsi- and contralateral striatum after 3 weeks and increase of AxD and MD in the ipsilateral striatum in rats with 6-OHDA striatal lesions (Perlbarg et al, 2018 ). That way, DTI applications to various PD models could contribute to the mapping of the underlying pathophysiology, together with DKI as a non-Gaussian DTI approach, which demonstrated microstructural alterations when applied to transgenic mice overexpressing human wildtype a-synuclein under the murine Thy-1 promoter, that is, increases in the striatum and thalamus after 3 months and in the substantia nigra after 6 months (Khairnar et al, 2017 ).…”

Section: Applications To Models Of Neurodegenerative Diseasesmentioning

confidence: 99%

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

et al. 2020

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The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.

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Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson’s disease evaluated with multimodal MRI

Cited by 33 publications

References 40 publications

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

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