Hypokinetic Movement Disorders: Parkinson Disease

2021 ◽  
pp. 576-582
Author(s):  
Sarah M. Tisel ◽  
Bryan T. Klassen
Keyword(s):  
Cell Death ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Movement Disorder ◽  
Movement Disorders ◽  
Dopaminergic Neurons ◽  
Microscopic Level ◽  
Rest Tremor ◽  
Macroscopic Level ◽  
Progressive Degeneration

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.

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
Keyword(s):  
Animal Models ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Movement Disorder ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Progressive Loss ◽  
Key Features ◽  
6 Hydroxydopamine

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.

Movement Disorders

2018 ◽  
pp. 393-429
Author(s):  
Andrea C. Adams
Keyword(s):  
Parkinson Disease ◽  
Movement Disorder ◽  
Movement Disorders ◽  
General Term ◽  
Voluntary Movements ◽  
P Movement

Movement disorders are neurologic syndromes in which movement is either excessive (hyperkinesia) or too little (hypokinesia). A general term used for both hyperkinesia and hypokinesia is dyskinesia, which is defined as difficulty performing voluntary movements. The prototypic hypokinetic movement disorder is Parkinson disease (PD). Other terms used to describe this movement disorder are bradykinesia (slowness of movement) and akinesia (loss of movement).

scholarly journals Earliest Mechanisms of Dopaminergic Neurons Sufferance in a Novel Slow Progressing Ex Vivo Model of Parkinson Disease in Rat Organotypic Cultures of Substantia Nigra

2019 ◽  
Vol 20 (9) ◽  
pp. 2224 ◽  
Author(s):  
Matteo Dal Ben ◽  
Rosario Bongiovanni ◽  
Simone Tuniz ◽  
Emanuela Fioriti ◽  
Claudio Tiribelli ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Ex Vivo Model ◽  
Redox Imbalance ◽  
Clinical Phase ◽  
Protein Clearance ◽  
Persistent Inflammation

The current treatments of Parkinson disease (PD) are ineffective mainly due to the poor understanding of the early events causing the decline of dopaminergic neurons (DOPAn). To overcome this problem, slow progressively degenerating models of PD allowing the study of the pre-clinical phase are crucial. We recreated in a short ex vivo time scale (96 h) all the features of human PD (needing dozens of years) by challenging organotypic culture of rat substantia nigra with low doses of rotenone. Thus, taking advantage of the existent knowledge, the model was used to perform a time-dependent comparative study of the principal possible causative molecular mechanisms undergoing DOPAn demise. Alteration in the redox state and inflammation started at 3 h, preceding the reduction in DOPAn number (pre-diagnosis phase). The number of DOPAn declined to levels compatible with diagnosis only at 12 h. The decline was accompanied by a persistent inflammation and redox imbalance. Significant microglia activation, apoptosis, a reduction in dopamine vesicle transporters, and the ubiquitination of misfolded protein clearance pathways were late (96 h, consequential) events. The work suggests inflammation and redox imbalance as simultaneous early mechanisms undergoing DOPAn sufferance, to be targeted for a causative treatment aimed to stop/delay PD.

scholarly journals The potential role of neuroinflammation and transcription factors in Parkinson disease

2017 ◽  
Vol 19 (1) ◽  
pp. 71-80 ◽  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Signaling Pathways ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Brain Regions ◽  
Death Domain

Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors—notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)—which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine—and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.

Toxic Equine Parkinsonism: An Immunohistochemical Study of 10 Horses With Nigropallidal Encephalomalacia

2011 ◽  
Vol 49 (2) ◽  
pp. 398-402 ◽  
Author(s):  
H. T. Chang ◽  
W. K. Rumbeiha ◽  
J. S. Patterson ◽  
B. Puschner ◽  
A. P. Knight
Keyword(s):  
Tyrosine Hydroxylase ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Globus Pallidus ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Large Animal Model ◽  
Substantia Nigra Pars Reticulata ◽  
Large Animal ◽  
Cytoplasmic Inclusions

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.

scholarly journals Neurotransmitters in the Basal Ganglia

1984 ◽  
Vol 11 (S1) ◽  
pp. 89-99 ◽  
Author(s):  
Edith G. McGeer ◽  
William A. Staines ◽  
Patrick L. McGeer
Keyword(s):  
Cell Death ◽  
Basal Ganglia ◽  
Substantia Nigra ◽  
Globus Pallidus ◽  
Dopaminergic Neurons ◽  
Pivotal Role ◽  
Substantia Nigra Pars Reticulata ◽  
Caudate Putamen ◽  
Motor Pathways ◽  
Stimulation Of

ABSTRACTThe literature is reviewed on the afferents and efferents of the caudate/putamen, globus pallidus and substantia nigra, and on the neurotransmitters occurring in the various tracts. Emphasis is placed upon the diverse roles played by GABA and glutamate as transmitters in motor pathways and upon the probability that the substantia nigra pars reticulata plays a pivotal role in the output of the basal ganglia. Excessive stimulation of the projection from the pedunculopontine tegmental area to the substantia nigra is shown to cause destruction of dopaminergic neurons in the latter nucleus, suggesting another possible mechanism for cell death in Parkinson’s disease.

Developmental cell death in dopaminergic neurons of the substantia nigra of mice

2000 ◽  
Vol 424 (3) ◽  
pp. 476-488 ◽  
Author(s):  
Vernice Jackson-Lewis ◽  
Miquel Vila ◽  
Ruth Djaldetti ◽  
Christelle Guegan ◽  
Gabriel Liberatore ◽  
...  
Keyword(s):  
Cell Death ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Developmental Cell Death

scholarly journals Progressive Degeneration of Dopaminergic Neurons through TRP Channel-Induced Cell Death

2014 ◽  
Vol 34 (17) ◽  
pp. 5738-5746 ◽  
Author(s):  
A. Nagarajan ◽  
Y. Ning ◽  
K. Reisner ◽  
Z. Buraei ◽  
J. P. Larsen ◽  
...  
Keyword(s):  
Cell Death ◽  
Dopaminergic Neurons ◽  
Trp Channel ◽  
Progressive Degeneration

scholarly journals Potential role of lactoferrin in early diagnostics and treatment of Parkinson disease

2020 ◽  
Vol 20 (1) ◽  
pp. 37-44
Author(s):  
Alexey V. Sokolov ◽  
Irina V. Miliukhina ◽  
Yury P. Belsky ◽  
Nataly V. Belska ◽  
Vadim B. Vasilyev
Keyword(s):  
Early Diagnosis ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Experimental Models ◽  
Control Group ◽  
Clear Understanding ◽  
Necrosis Factor Alpha ◽  
Positive Effects ◽  
Factor Alpha

Incidence of Parkinson disease progressively grows with increasing age and percentage of elderly people in the global population. Clear understanding of the causes of dopaminergic neurons death in Substantia nigra and Parkinson disease pathogenesis are currently absent, not speaking of an efficient therapy. However, an early diagnosis of dopaminergic neurons degeneration and prescription of dopamine replacement therapy significantly slow down the rate of symptoms progression. An increased concentration of iron in Substantia nigra of Parkinson disease patients has been shown in several studies. In this review we summarized the data concerning a potential significance of lactoferrin, the iron-binding protein of exocrine secretions and neutrophils, for early diagnosis and treatment of Parkinson disease. Salivary and lacrimal lactoferrin levels in Parkinson disease patients were higher than those observed in the control group. Plasma levels of lactoferrin inversely correlated with Parkinson disease severity even after treatment with Levodopa, a dopamine agonist, and with monoaminooxidase inhibitors. Lactoferrin levels in cerebrospinal fluid of Parkinson disease patients negatively correlated with the tumor necrosis factor-alpha concentration. Lactoferrin treatment of rodents with several experimental models of Parkinson disease (induced by rotenone, MPTP) protected neurons and mitigated the symptoms of neurodegeneration. Some contradictions about the positive effects of lactoferrin as a remedy in Parkinson disease animal models and possible participation of lactoferrin in accumulation of iron in neurons are discussed.

Sign in / Sign up

Export Citation Format

Share Document