scholarly journals Lithium protects against oxidative stress-mediated cell death in α-synuclein-overexpressing in vitro and in vivo models of Parkinson's disease

2011 ◽  
Vol 89 (10) ◽  
pp. 1666-1675 ◽  
Author(s):  
Yong-Hwan Kim ◽  
Anand Rane ◽  
Stephanie Lussier ◽  
Julie K. Andersen
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
In Vivo Models

Clioquinol Protects Against Cell Death in Parkinson’s Disease Models In Vivo and In Vitro

2009 ◽  
pp. 431-442 ◽  
Author(s):  
Simon Wilkins ◽  
Colin L. Masters ◽  
Ashley I. Bush ◽  
Robert A. Cherny ◽  
David I. Finkelstein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Disease Models

scholarly journals Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson’s Disease

2018 ◽  
Vol 66 (4) ◽  
pp. 856-865 ◽  
Author(s):  
Fabiana Morroni ◽  
Giulia Sita ◽  
Alice Djemil ◽  
Massimo D’Amico ◽  
Letizia Pruccoli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
In Vivo Models

scholarly journals Ablation of RIP3 protects from dopaminergic neurodegeneration in experimental Parkinson’s disease

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Pedro A. Dionísio ◽  
Sara R. Oliveira ◽  
Maria M. Gaspar ◽  
Maria J. Gama ◽  
Margarida Castro-Caldas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Cultured Cells ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Cultures ◽  
Interacting Protein ◽  
Dopaminergic Neurodegeneration

Abstract Parkinson’s disease (PD) is driven by dopaminergic neurodegeneration in the substantia nigra pars compacta (SN) and striatum. Although apoptosis is considered the main neurodegenerative mechanism, other cell death pathways may be involved. In this regard, necroptosis is a regulated form of cell death dependent on receptor interacting protein 3 (RIP3), a protein also implicated in apoptosis and inflammation independently of its pro-necroptotic activity. Here, we explored the role of RIP3 genetic deletion in in vivo and in vitro PD models. Firstly, wild-type (Wt) and RIP3 knockout (RIP3ko) mice were injected intraperitoneally with MPTP (40 mg/kg, i.p.), and sacrificed after either 6 or 30 days. RIP3ko protected from dopaminergic neurodegeneration in the SN of MPTP-injected mice, but this effect was independent of necroptosis. In keeping with this, necrostatin-1s (10 mg/kg/day, i.p.) did not afford full neuroprotection. Moreover, MPTP led to DNA fragmentation, caspase-3 activation, lipid peroxidation and BAX expression in Wt mice, in the absence of caspase-8 cleavage, suggesting intrinsic apoptosis. This was mimicked in primary cortical neuronal cultures exposed to the active MPTP metabolite. RIP3 deficiency in cultured cells and in mouse brain abrogated all phenotypes. Curiously, astrogliosis was increased in the striatum of MPTP-injected Wt mice and further exacerbated in RIP3ko mice. This was accompanied by absence of microgliosis and reposition of glial cell line-derived neurotrophic factor (GDNF) levels in the striata of MPTP-injected RIP3ko mice when compared to MPTP-injected Wt mice, which in turn showed a massive GDNF decrease. RIP3ko primary mixed glial cultures also presented decreased expression of inflammation-related genes upon inflammatory stimulation. These findings hint at possible undescribed non-necroptotic roles for RIP3 in inflammation and MPTP-driven cell death, which can contribute to PD progression.

scholarly journals Norfluoxetine Prevents Degeneration of Dopamine Neurons by Inhibiting Microglia-Derived Oxidative Stress in an MPTP Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Kyung In Kim ◽  
Young Cheul Chung ◽  
Byung Kwan Jin
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Microglial Activation ◽  
Dopamine Neurons ◽  
Activated Microglia ◽  
Nigrostriatal Dopamine Neurons

Neuroinflammation is the neuropathological feature of Parkinson’s disease (PD) and causes microglial activation and activated microglia-derived oxidative stress in the PD patients and PD animal models, resulting in neurodegeneration. The present study examined whether norfluoxetine (a metabolite of fluoxetine) could regulate neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD and rescue dopamine neurons. Analysis by tyrosine hydroxylase (TH) immunohistochemistry demonstrated that norfluoxetine prevents degeneration of nigrostriatal dopamine neurons in vivo in MPTP-lesioned mice compared to vehicle-treated MPTP-lesioned control mice. MAC-1 immunostaining and hydroethidine histochemical staining showed that norfluoxetine neuroprotection is accompanied by inhibiting MPTP-induced microglial activation and activated microglia-derived reactive oxygen species production in vivo, respectively. In the separate experiments, treatment with norfluoxetine inhibited NADPH oxidase activation and nitrate production in LPS-treated cortical microglial cultures in vitro. Collectively, these in vivo and in vitro results suggest that norfluoxetine could be employed as a novel therapeutic agent for treating PD, which is associated with neuroinflammation and microglia-derived oxidative stress.

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