Assessment of Oxidative Stress and Treatment with a Novel Antioxidant Compound in a Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 76 ◽  
pp. S79-S80
Author(s):  
Lisa M. Caputo ◽  
Chad E. Beyer ◽  
Michael P. Neary ◽  
Michael J. Zigmond ◽  
Sandra L. Castro ◽  
...  
2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Kyung In Kim ◽  
Young Cheul Chung ◽  
Byung Kwan Jin

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Thuong Manh Le ◽  
Koji Hashida ◽  
Hieu Minh Ta ◽  
Mika Takarada-Iemata ◽  
Koichi Kokame ◽  
...  

Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments usingHerpud1+/+andHerpud1−/−mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes ofHerpud1−/−mice than in the astrocytes ofHerpud1+/+mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP+, an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion ofHerpud1may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.


2021 ◽  
Author(s):  
Cong Liu ◽  
Wenjuan Wang ◽  
Hao Li ◽  
Jiangang Liu ◽  
Peng Zhang ◽  
...  

Parkinson's disease is the second most common neurodegenerative disease. Researches have shown that oxidative stress and apoptosis play an important role in Parkinson's disease process. Isoquercitrin (quercetin-3-O-β-D-glucopyranoside) is a natural...


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