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 Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

2015 ◽  
Vol 73 (7) ◽  
pp. 616-623 ◽  
Author(s):  
Taysa Bervian Bassani ◽  
Maria A.B.F. Vital ◽  
Laryssa K. Rauh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Inflammatory Process ◽  
Epidemiological Studies ◽  
Substantia Nigra Pars Compacta ◽  
Fine Motor ◽  
Progressive Degeneration ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

Effect of monocrotophos, an organophosphorus insecticide, on the striatal dopaminergic system in a mouse model of Parkinson’s disease

2014 ◽  
Vol 32 (7) ◽  
pp. 1153-1165 ◽  
Author(s):  
Shaheen Jafri Ali ◽  
Padmanabhan Sharda Rajini
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Dopaminergic Neurons ◽  
Dopaminergic System ◽  
Nigrostriatal System ◽  
Low Concentrations ◽  
Repeated Doses ◽  
Mouse Model System ◽  
Neurobehavioral Deficits

Our earlier study had shown that low concentrations of monocrotophos (MCP) elicited dopaminergic features of Parkinson’s disease (PD) in the nematode Caenorhabditis elegans. In the present study, the effect of low doses of MCP on the striatal dopaminergic neurons was investigated using the mouse model system. MCP was initially screened for its ability to cause any neurobehavioral deficits and alterations in the dopaminergic system in Swiss albino mice, aged 8 weeks and weighing 25–30 g, with repeated doses at 0.3 and 0.6 mg/kg body weight (b.w.)/day for 7 days and 30 days. Mice were treated with four intraperitoneal injections for every 2 h with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 14 mg/kg b.w. MCP was administered to these mice at the above-mentioned doses for 7 days. Mice administered with MCP alone revealed a significant ( p < 0.05) reduction in the dopamine (DA) content at both 7 and 30 days and showed a significant ( p < 0.05) increase in neurobehavioral deficits. Interestingly, when MCP was administered for 7 days to MPTP-treated mice, further significant decrease in both DA content and increase in neurobehavioral deficits were apparent. The extent of reactive oxygen species and lipid peroxidation were markedly increased, while the ratio of reduced to oxidized glutathione levels were significantly decreased ( p < 0.05) in the treated mice as compared to the control. Significant histopathological alterations and a marked reduction in the number of tyrosine hydroxylase positive cells were evident in striatum of mice treated with higher doses of MCP. These changes were comparable to that seen in mice treated with MPTP and post-administered lower doses of MCP. Our findings suggest that MCP per se has the propensity to induce pathological changes in the dopaminergic neurons as well as augment the degeneration in a compromised nigrostriatal system such as that in PD.

scholarly journals Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease

2015 ◽  
Vol 82 ◽  
pp. 430-444 ◽  
Author(s):  
G. Cisbani ◽  
J. Drouin-Ouellet ◽  
C. Gibrat ◽  
M. Saint-Pierre ◽  
M. Lagacé ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Dopaminergic System

scholarly journals Bone loss caused by dopaminergic degeneration and levodopa treatment in Parkinson’s disease model mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kazuaki Handa ◽  
Shuichi Kiyohara ◽  
Tomoyuki Yamakawa ◽  
Koji Ishikawa ◽  
Masahiro Hosonuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Dopaminergic System ◽  
Disease Model ◽  
Gonadal Steroid ◽  
Independent Functions ◽  
Standard Medication ◽  
Dopaminergic Degeneration

Abstract Accumulating evidence have shown the association of Parkinson’s disease (PD) with osteoporosis. Bone loss in PD patients, considered to be multifactorial and a result of motor disfunction, is a hallmark symptom that causes immobility and decreased muscle strength, as well as malnutrition and medication. However, no known experimental evidence has been presented showing deleterious effects of anti-PD drugs on bone or involvement of dopaminergic degeneration in bone metabolism. Here, we show that osteoporosis associated with PD is caused by dopaminergic degeneration itself, with no deficit of motor activity, as well as treatment with levodopa, the current gold-standard medication for affected patients. Our findings show that neurotoxin-induced dopaminergic degeneration resulted in bone loss due to accelerated osteoclastogenesis and suppressed bone formation, which was associated with elevated prolactin. On the other hand, using an experimental model of postmenopausal osteoporosis, dopaminergic degeneration did not result in exacerbation of bone loss due to estrogen deficiency, but rather reduction of bone loss. Thus, this study provides evidence for the regulation of bone metabolism by the dopaminergic system through both gonadal steroid hormone-dependent and -independent functions, leading to possible early detection of osteoporosis development in individuals with PD.

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 Gastrodin Protects Apoptotic Dopaminergic Neurons in a Toxin-Induced Parkinson’s Disease Model

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Hemant Kumar ◽  
In-Su Kim ◽  
Sandeep Vasant More ◽  
Byung-Wook Kim ◽  
Young-Yil Bahk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Disease Model ◽  
Motor Impairment ◽  
Protective Effects ◽  
Dopamine Depletion ◽  
Active Constituent ◽  
Neuroprotective Effects ◽  
Phenolic Glucoside

Gastrodia elata(GE) Blume is one of the most important traditional plants in Oriental countries and has been used for centuries to improve various conditions. The phenolic glucoside gastrodin is an active constituent of GE. The aim of this study was to investigate the neuroprotective role of gastrodin in 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson’s disease (PD), respectively. Gastrodin significantly and dose dependently protected dopaminergic neurons against neurotoxicity through regulating free radicals, Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) in SH-SY5Y cells stressed with MPP+. Gastrodin also showed neuroprotective effects in the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor impairment in the pole and rotarod tests, respectively. Consistent with this finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis caused by MPTP as assessed by immunohistochemistry and immunoblotting in the substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic activities in these brain areas. These results strongly suggest that gastrodin has protective effects in experimental PD models and that it may be developed as a clinical candidate to ameliorate PD symptoms.

Melatonin/polydopamine nanostructures for collective neuroprotection-based Parkinson's disease therapy

2020 ◽  
Vol 8 (5) ◽  
pp. 1345-1363 ◽  
Author(s):  
Anup K. Srivastava ◽  
Subhasree Roy Choudhury ◽  
Surajit Karmakar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Disease Models ◽  
Disease Therapy ◽  
Apoptotic Effect ◽  
Anti Inflammatory

The bioinspired melatonin/polydopamine nanostructures confer superior neuroprotection in dopaminergic neurons via anti-oxidative, anti-inflammatory and anti-apoptotic effect in Parkinson's disease models.

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.

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