scholarly journals Da-Bu-Yin-Wan and Qian-Zheng-San to Neuroprotect the Mouse Model of Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Gang Gong ◽  
Hong-Mei Sun ◽  
Yi Zhang ◽  
Shu-Jing Zhang ◽  
Yu-Shan Gao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neuroprotective Effect ◽  
Firefly Luciferase ◽  
Dopamine Neurons ◽  
Behavioral Impairment ◽  
Neuroprotective Effects ◽  
Atp Level ◽  
Protein Levels

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson’s disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATPchannel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATPchannel subunit expressions.

scholarly journals Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

2015 ◽  
Vol 26 (24) ◽  
pp. 4478-4491 ◽  
Author(s):  
BK. Binukumar ◽  
Varsha Shukla ◽  
Niranjana D. Amin ◽  
Philip Grant ◽  
M. Bhaskar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Selective Inhibition ◽  
Motor Dysfunction ◽  
Dopamine Neurons ◽  
Dopamine Depletion ◽  
Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 ­hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

scholarly journals Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

2021 ◽  
Author(s):  
Xiao Yan Sheng ◽  
Shui Yuan Yang ◽  
Xiao Min Wen ◽  
Xin Zhang ◽  
Yong Feng Ye ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Motor Behavior ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Dopamine Neurons ◽  
Therapeutic Modality ◽  
Neuroprotective Effects

Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

scholarly journals Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaoyan Sheng ◽  
Shuiyuan Yang ◽  
Xiaomin Wen ◽  
Xin Zhang ◽  
Yongfeng Ye ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Motor Behavior ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Dopamine Neurons ◽  
Therapeutic Modality ◽  
Neuroprotective Effects

Abstract Background Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo. Methods In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively. Results Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway. Conclusions SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

Potential neuroprotective effect of androst-5-ene-3β, 17β-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model

2018 ◽  
Vol 233 (8) ◽  
pp. 5981-6000 ◽  
Author(s):  
Rania M. Salama ◽  
Mariane G. Tadros ◽  
Mona F. Schaalan ◽  
Nevine Bahaa ◽  
Ahmed M. Abdel-tawab ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Rat Model ◽  
Neuroprotective Effect

scholarly journals A pH-eQTL interaction at the RIT2-SYT4 Parkinson's disease risk locus in the substantia nigra

2020 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Leon French
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Human Brain ◽  
Disease Risk ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Postmortem Human Brain ◽  
Increased Risk

BACKGROUND: Parkinson's disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson's disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. OBJECTIVE: To assess pH associations at the RIT2-SYT4 locus. METHODS: Linear models to examine two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. RESULTS: Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain. Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. CONCLUSIONS: These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.

scholarly journals Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson's Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 206 ◽  
Author(s):  
Tsung-Hsun Hsieh ◽  
Chi-Wei Kuo ◽  
Kai-Hsuan Hsieh ◽  
Meng-Jyh Shieh ◽  
Chih-Wei Peng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Dopamine Neurons ◽  
Motor Symptoms ◽  
Neuroprotective Effects ◽  
Motor Functions ◽  
Term Administration ◽  
Nigrostriatal Dopamine Neurons

Parkinson’s disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.

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