scholarly journals The c-Abl inhibitor, Nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Senthilkumar S. Karuppagounder ◽  
Saurav Brahmachari ◽  
Yunjong Lee ◽  
Valina L. Dawson ◽  
Ted M. Dawson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic Neurons ◽  
Preclinical Animal Model

scholarly journals Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
A. Machado ◽  
A. J. Herrera ◽  
J. L. Venero ◽  
M. Santiago ◽  
R. M. de Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic Neurons ◽  
Inflammatory Process ◽  
Dopaminergic System ◽  
Neuronal System ◽  
Dopamine Depletion ◽  
Anti Inflammatory ◽  
Dopaminergic Degeneration

We have developed an animal model of degeneration of the nigrostriatal dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD). The implication of neuroinflammation on this disease was originally established in 1988, when the presence of activated microglia in the substantia nigra (SN) of parkinsonians was reported by McGeer et al. Neuroinflammation could be involved in the progression of the disease or even has more direct implications. We injected 2 μg of the potent proinflammatory compound lipopolysaccharide (LPS) in different areas of the CNS, finding that SN displayed the highest inflammatory response and that dopaminergic (body) neurons showed a special and specific sensitivity to this process with the induction of selective dopaminergic degeneration. Neurodegeneration is induced by inflammation since it is prevented by anti-inflammatory compounds. The special sensitivity of dopaminergic neurons seems to be related to the endogenous dopaminergic content, since it is overcome by dopamine depletion. Compounds that activate microglia or induce inflammation have similar effects to LPS. This model suggest that inflammation is an important component of the degeneration of the nigrostriatal dopaminergic system, probably also in PD. Anti-inflammatory treatments could be useful to prevent or slow down the rate of dopaminergic degeneration in this disease.

scholarly journals Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease

2016 ◽  
Vol 11 (2) ◽  
pp. 259-278 ◽  
Author(s):  
Anamitra Ghosh ◽  
Monica R. Langley ◽  
Dilshan S. Harischandra ◽  
Matthew L Neal ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Preclinical Animal Model ◽  
Dopaminergic Neurodegeneration

scholarly journals Synergistic effect of combined GDNF and Amodiaquine attenuates behavioral deficits and protect dopaminergic neurons of Parkinson’s disease animal model through tyrosine kinase Ret receptor

2020 ◽  
Author(s):  
Piniel Kambey ◽  
Dianshuai Gao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Combined Therapy ◽  
Behavioral Deficits ◽  
Neuro Protection

Abstract Parkinson’s disease (PD) is one among the most leading neurodegenerative disease after Alzheimer’s disease, with a prevalence of approximately 0.5–1% among those 65–69 years of age. Efforts to vitiate this disease are ongoing, and several treatment modes such as Glial cell line-derived neurotrophic factor (GDNF) have been in place since 1993. Glial cell line derived neurotrophic factor (GDNF) protects, regenerates, and improves the metabolism of substantia nigra pars compacta neurons (SNpc), and it increases the high-affinity dopamine uptake. It has been recently reported that amodiquine could attenuates the behavioral deficits of an animal model of Parkinson’s disease, nevertheless it mechanism is obscure. We sought to demonstrate the mechanism of neuro-protection effect of amodiquine and ascertain its corroborative effect when used togather with GDNF. We show herein that combined therapy (GDNF and amodiaquine) ameliorated behavioral deficits of PD animal models as compared to single-factor treatment. TH positive neurons increased significantly upon combined therapy treatment, and besides, GDNF and amodiaquine interact functionally to protect dopaminergic neurons through the PIK-3/Akt pathway. We also found that combined therapy (GDNF and amodiaquine) mediates its action through a distinct trans-membrane tyrosine kinase Ret receptor by amplifying its effect. Slight elevated aspartate aminotransferase (AST) were noticed in amodiaquine treated groups, alarming the bio-utility. These findings collectively suggest an interplay between GDNF and amodiaquine and co-express to exert neuronal protection hence a promising approach in PD therapy. Despite its undisputed effect on neuro-protection, we report that amodiaquine may not be safe, particularly in translation to human beings' trial settings.

Inhibition of proteasome function in rat nigrostriatal dopaminergic neurons as an animal model of Parkinson’s disease for studying neuroprotective compounds

2010 ◽  
Vol 62 ◽  
pp. 33
Author(s):  
Elżbieta Lorenc-Koci ◽  
Tomasz Lenda ◽  
Helena Domin ◽  
Danuta Jantas ◽  
Maria Śmiałowska ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic Neurons

Rutin Protects Dopaminergic Neurons from Oxidative Stress in an Animal Model of Parkinson’s Disease

2011 ◽  
Vol 22 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Mohd. Moshahid Khan ◽  
Syed Shadab Raza ◽  
Hayate Javed ◽  
Ajmal Ahmad ◽  
Andleeb Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic Neurons

scholarly journals To be or not to be pink(1): contradictory findings in an animal model for Parkinson’s disease

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ria de Haas ◽  
Lisa C M W Heltzel ◽  
Denise Tax ◽  
Petra van den Broek ◽  
Hilbert Steenbreker ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
In Vivo Microdialysis ◽  
Substantia Nigra Pars Compacta ◽  
Laboratory Animals ◽  
Motor Deficits

Abstract The PTEN-induced putative kinase 1 knockout rat (Pink1−/−) is marketed as an established model for Parkinson’s disease, characterized by development of motor deficits and progressive degeneration of half the dopaminergic neurons in the substantia nigra pars compacta by 8 months of age. In this study, we address our concerns about the reproducibility of the Pink1−/− rat model. We evaluated behavioural function, number of substantia nigra dopaminergic neurons and extracellular striatal dopamine concentrations by in vivo microdialysis. Strikingly, we and others failed to observe any loss of dopaminergic neurons in 8-month-old male Pink1−/− rats. To understand this variability, we compared key experimental parameters from the different studies and provide explanations for contradictory findings. Although Pink1−/− rats developed behavioural deficits, these could not be attributed to nigrostriatal degeneration as there was no loss of dopaminergic neurons in the substantia nigra and no changes in neurotransmitter levels in the striatum. To maximize the benefit of Parkinson’s disease research and limit the unnecessary use of laboratory animals, it is essential that the research community is aware of the limits of this animal model. Additional research is needed to identify reasons for inconsistency between Pink1−/− rat colonies and why degeneration in the substantia nigra is not consistent.

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