scholarly journals Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141877743 ◽  
Author(s):  
Xian-Si Zeng ◽  
Wen-Shuo Geng ◽  
Jin-Jing Jia

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.

Author(s):  
В.В. Голоборщева ◽  
Н.А. Воронина ◽  
Р.К. Овчинников ◽  
В.Г. Кучеряну ◽  
С.Г. Морозов

Использование экспериментальных моделей на животных является чрезвычайно ценным методом изучения патогенеза заболеваний человека и используется для разработки их эффективной терапии. В отличие от изолированных моделей in vitro, использование животных в качестве модельной системы оказалось более продуктивным для изучения мультифакториальных заболеваний или болезней, влияющих на несколько систем организма. Данный метод особенно актуален в отношении использования моделей in vivo для понимания патофизиологических механизмов расстройств центральной нервной системы, включая эпилепсию, рассеянный склероз и нейродегенеративные заболевания. Одним из ключевых среди нейродегенеративных расстройств является болезнь Паркинсона (БП) - хроническое прогрессирующее заболевание, вызванное недостатком дофамина в стриатуме головного мозга в результате гибели дофаминергических (ДА) нейронов чёрной субстанции (ЧС). В настоящее время для воспроизведения у животных основных характеристик БП, включая двигательные нарушения, прогрессирующую потерю ДА-ергических нейронов в компактной части черной субстанции и образование телец Леви, широко используют соединение 1-метил-4-фенил-1,2,3,6-тетрагидропиридин (МФТП). В этом обзоре будут охарактеризованы популярные экспериментальные модели для изучения БП, в которых в рамках исследований вводили нейротоксин МФТП, с целью систематизировать уже имеющийся научный опыт, а также способствовать развитию моделирования паркинсонического синдрома. The use of experimental animal models to understand human diseases and the potential treatments has been extremely valuable and has led to many significant advances in medicine. In contrast to isolated in vitro models, the use of animals as a model system has proven to be more productive for studying of multi-factorial diseases or diseases that affect several human systems. This method is particularly relevant for the use of animal models to understand the pathophysiology of central nervous system disorders such as meningitis, multiple sclerosis, and neurodegenerative disorders. Parkinson’s disease (PD), a chronic progressive illness, caused by a lack of dopamine (DA) in the striatum due to the death of DAergic neurons in the substantia nigra (SN), is one of the neurodegenerative key disorders. Nowadays, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a widely used compound to reproduce the main characteristics of PD in animals, which include motor disorders, progressive loss of DA-neurons in the substantia nigra pars compacta and the formation of Lewy bodies. In this review, we observe MPTP-treated popular mouse models for the PD studying in order to systematize the existing scientific experience, as well as to promote the development of parkinsonian syndrome modeling.


2021 ◽  
pp. 576-582
Author(s):  
Sarah M. Tisel ◽  
Bryan T. Klassen

Parkinson disease (PD) is the classic hypokinetic movement disorder and one of the most common and widely recognized neurodegenerative conditions. PD is distinct from parkinsonism, a term that refers to a syndrome of rest tremor, bradykinesia, rigidity, and postural instability. The mechanism behind the progressive degeneration and cell death that result in PD is not precisely understood. Substantia nigra depigmentation occurs on a macroscopic level and loss of dopaminergic neurons and gliosis on a microscopic level.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
François-Xavier Blaudin de Thé ◽  
Hocine Rekaik ◽  
Alain Prochiantz ◽  
Julia Fuchs ◽  
Rajiv L. Joshi

A number of transcription factors, including En1/2, Foxa1/2, Lmx1a/b, Nurr1, Otx2, and Pitx3, with key roles in midbrain dopaminergic (mDA) neuron development, also regulate adult mDA neuron survival and physiology. Mouse models with targeted disruption of some of these genes display several features reminiscent of Parkinson disease (PD), in particular the selective and progressive loss of mDA neurons in the substantia nigra pars compacta (SNpc). The characterization of these animal models has provided valuable insights into various mechanisms of PD pathogenesis. Therefore, the dissection of the mechanisms and survival signalling pathways engaged by these transcription factors to protect mDA neuron from degeneration can suggest novel therapeutic strategies. The work on En1/2-mediated neuroprotection also highlights the potential of protein transduction technology for neuroprotective approaches in PD.


2011 ◽  
Vol 49 (2) ◽  
pp. 398-402 ◽  
Author(s):  
H. T. Chang ◽  
W. K. Rumbeiha ◽  
J. S. Patterson ◽  
B. Puschner ◽  
A. P. Knight

Chronic ingestion of yellow star thistle ( Centaurea solstitialis) or Russian knapweed ( Acroptilon repens) causes nigropallidal encephalomalacia (NPE) in horses with an abrupt onset of neurologic signs characterized by dystonia of lips and tongue, inability to prehend food, depression, and locomotor deficits. The objectives of this study were to reexamine the pathologic alterations of NPE and to conduct an immunohistochemistry study using antibodies to tyrosine hydroxylase and α-synuclein, to determine whether NPE brains show histopathologic features resembling those in human Parkinson disease. Results confirm that the NPE lesions are located within the substantia nigra pars reticulata, sparing the cell bodies of the dopaminergic neurons in the substantia nigra pars compacta, and in the rostral portion of the globus pallidus, with partial disruption of dopaminergic (tyrosine hydroxylase–positive) fibers passing through the globus pallidus. No abnormal cytoplasmic inclusions like the Lewy bodies of human Parkinson disease were seen in these NPE brains. These findings indicate that equine NPE may serve as a large animal model of environmentally acquired toxic parkinsonism, with clinical phenotype directly attributable to lesions in globus pallidus and substantia nigra pars reticulata rather than to the destruction of dopaminergic neurons.


2005 ◽  
Vol 26 (5) ◽  
pp. 869-881 ◽  
Author(s):  
Nicola Berretta ◽  
Peter S. Freestone ◽  
Ezia Guatteo ◽  
Denis de Castro ◽  
Raffaella Geracitano ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3368
Author(s):  
Gian-Carlo Eyer ◽  
Stefano Di Santo ◽  
Ekkehard Hewer ◽  
Lukas Andereggen ◽  
Stefanie Seiler ◽  
...  

Parkinson’s disease is mainly characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Together with the small number, the high vulnerability of the dopaminergic neurons is a major pathogenic culprit of Parkinson’s disease. Our previous findings of a higher survival of dopaminergic neurons in the substantia nigra co-expressing Nogo-A in an animal model of Parkinson’s disease suggested that Nogo-A may be associated with dopaminergic neurons resilience against Parkinson’s disease neurodegeneration. In the present study, we have addressed the expression of Nogo-A in the dopaminergic neurons in the substantia nigra in postmortem specimens of diseased and non-diseased subjects of different ages. For this purpose, in a collaborative effort we developed a tissue micro array (TMA) that allows for simultaneous staining of many samples in a single run. Interestingly, and in contrast to the observations gathered during normal aging and in the animal model of Parkinson’s disease, increasing age was significantly associated with a lower co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson’s disease. In sum, while Nogo-A expression in dopaminergic neurons is higher with increasing age, the opposite is the case in Parkinson’s disease. These observations suggest that Nogo-A might play a substantial role in the vulnerability of dopaminergic neurons in Parkinson’s disease.


2021 ◽  
Vol 15 ◽  
Author(s):  
Yong Hui Nies ◽  
Nor Haliza Mohamad Najib ◽  
Wei Ling Lim ◽  
Mohd Amir Kamaruzzaman ◽  
Mohamad Fairuz Yahaya ◽  
...  

Parkinson’s disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.


2021 ◽  
Vol 15 ◽  
Author(s):  
Alexandra Petiet

Parkinson’s disease (PD) is a major neurodegenerative disease characterized by massive degeneration of the dopaminergic neurons in the substantia nigra pars compacta, α-synuclein-containing Lewy bodies, and neuroinflammation. Magnetic resonance (MR) imaging plays a crucial role in the diagnosis and monitoring of disease progression and treatment. A variety of MR methods are available to characterize neurodegeneration and other disease features such as iron accumulation and metabolic changes in animal models of PD. This review aims at giving an overview of how those physiopathological features of PD have been investigated using various MR methods in rodent models. Toxin-based and genetic-based models of PD are first described. MR methods for neurodegeneration evaluation, iron load, and metabolism alterations are then detailed, and the main findings are provided in those models. Ultimately, future directions are suggested for neuroinflammation and neuromelanin evaluations in new animal models.


Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.


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