Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation

The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated.

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Catalpol Exerts Neuroprotective Effect on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Mouse Model of Parkinson’s Disease and the Underlying Mechanisms

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2713 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1506-1516

Author(s):

Xueqian Li ◽

Chengzhi Zhao

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Performance Test ◽

Behavioral Science ◽

Neuroprotective Effect ◽

Inflammatory Factors ◽

Sod Activity ◽

Novel Approach ◽

Underlying Mechanisms

Our current study aimed to assess the preventive and therapeutic impacts of catalpol on Parkinson’s disease (PD) and its possible mechanism. In this study, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were employed to establish a PD model and then treated with catalpol followed by analysis of behavioral science by open field test, pole-climbing assay and rotarod performance test, ROS and SOD activity and expression of TH, DAT, VEGF and GAP43 by western blot or immunofluorescence. The results disclosed that catalpol can ameliorate the MPTP-triggered loss of dopamine (DA)-producing neurons, while it was able to enhance the expression of tyrosine hydroxylase (TH), accompanied by the activation of astrocytes and microglia. Catalpol treatment significantly retarded the oxidative stress induced by MPTP, along with elevated levels of VEGF and growth-associated protein 4 (GAP43). Additionally, catalpol treatment activated the MKK4/JNK/c-Jun signal pathway in PD mouse model, accompanied by reduced secretion of pro-inflammatory factors. Catalpol executed the anti-apoptotic and anti-oxidant impacts on MPTP-induced Parkinson’s model, suggesting that it might be a novel approach for treating PD in the future.

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Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease

NeuroToxicology ◽

10.1016/j.neuro.2013.03.004 ◽

2013 ◽

Vol 36 ◽

pp. 63-71 ◽

Cited By ~ 91

Author(s):

Fabiana Morroni ◽

Andrea Tarozzi ◽

Giulia Sita ◽

Cecilia Bolondi ◽

Juan Manuel Zolezzi Moraga ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Neuroprotective Effect ◽

6 Hydroxydopamine

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

Mediators of Inflammation ◽

10.1155/2018/4591289 ◽

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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