Protective effect of estrogen on apoptosis in a cell culture model of Parkinson's disease

Objectives: The protective effect of estrogen on the neurons in Parkinson’s disease (PD) is unclear. The present study aimed to investigate the effect of estrogen on the apoptosis and dopaminergic function on a cultured cell model of PD. Methods: The PD model was established by addition of 1-methyl-4-phenylpyridinium (MPP+) to PC12 cell culture. Estrogen was added to cell groups with MPP+ (Estrogen+MPP+), and without MPP+ (Estrogen only group). Cell viability, content of tyrosine hydroxylase (TH), apoptosis ratio, expression of apoptosis-suppression protein Bcl-x and apoptosis-acceleration protein IL-1 beta converting enzyme (ICE) were measured. Results: Cell viability in the Estrogen+MPP+ group was similar to the control group but was higher than in the MPP+ group (P < 0.05). The apoptosis ratios in the Estrogen+MPP+ group (33.6%), and the control group (31.3%), were also similar, but it was lower than in the MPP+ group (63.5%, P < 0.05). Concentrations of Bcl-x were higher in the Estrogen+MPP+ group, whereas ICE concentrations were lower than in the MPP+ group (P < 0.05). Conclusions: Estrogen suppresses apoptosis and improves cell viability in MPP+ induced injuries in the PC12 cells. The beneficial effects of estrogen on the PD model are due to the suppression of pro-apoptotic protein ICE, and stimulation of anti-apoptotic protein Bcl-x.

Download Full-text

Chinese Herbal Complex ‘Bu Shen Jie Du Fang’ (BSJDF) Modulated Autophagy in an MPP+-Induced Cell Model of Parkinson’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8920813 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Cuifang Liu ◽

Xiaobo Huang ◽

Shengxiang Qiu ◽

Wenqiang Chen ◽

Weihong Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Parkinson Disease ◽

Cell Model ◽

Cell Counting ◽

Functional Coupling ◽

Motor Impairments ◽

Chinese Herbal ◽

Cell Counts ◽

Cell Groups

Autophagy plays an important role in the development of Parkinson disease (PD). Previous studies showed that autophagy could protect cells from α-synuclein toxicity and promote functional coupling of mitochondria. But it is still a question whether modulating autophagy can be used to treat PD. In traditional Chinese medicine, a specific Chinese herbal complex called Bu Shen Jie Du Fang (BSJDF) has a long history of treating motor impairments similar to Parkinson disease, while its mechanism is still unclear. As a pilot study, we aimed to evaluate the efficacy and its mechanism of Bu Shen Jie Du Fang in an MPP+-induced cell model of Parkinson’s disease. And the phase contrast microscope (PCM) revealed that the BSJDF group had the greatest surviving cell counts compared with all other treated cell groups except the normal group. And Cell Counting Kit 8 (CCK8) assays showed a similar result. In BSJDF group, 3.7 ×107 cells/dish was identified by hemocytometer counts, which was significantly higher than other groups except the normal cells (p<0.05). In the BSJDF group, autophagy can be observed by transmission electron microscopy (TEM). Protein expression of Atg12 and LC3 in the BSJDF group was upregulated compared to the PD model group (p<0.05). Atg12 mRNA expression was also upregulated in the BSJDF group (p<0.05). In conclusion, our study indicated that the therapeutic mechanisms of BSJDF may be mediated by stimulating autophagy, and modulating autophagy can be used to treat PD.

Download Full-text

Protective Effects ofStreblus asperLeaf Extract on H2O2-Induced ROS in SK-N-SH Cells and MPTP-Induced Parkinson’s Disease-Like Symptoms in C57BL/6 Mouse

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/970354 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

Kanathip Singsai ◽

Tarinee Akaravichien ◽

Veerapol Kukongviriyapan ◽

Jintana Sattayasai

Keyword(s):

Parkinson’S Disease ◽

Cell Culture ◽

Parkinson's Disease ◽

Social Recognition ◽

Control Group ◽

Protective Effects ◽

Concurrent Treatment ◽

Intracellular Ros ◽

Balance Ability ◽

Streblus Asper

This study investigated the effects ofStreblus asperleaf extract (SA) on reactive oxygen species (ROS) in SK-N-SH cell culture and on motor functions and behaviors in MPTP-treated C57BL/6 mice. SK-N-SH cell viability after incubation with SA for 24 h was measured by MTT assay. Intracellular ROS levels of SK-N-SH cells were quantified after pretreatment with SA (0, 200, 600, and 1000 µg/mL) in the presence of H2O2(300 µM). Male C57BL/6 mice were force-fed with water or 200 mg/kg/day SA for 32 days. Intraperitoneal injection of MPTP was used to induce Parkinson’s disease-like symptoms. Catalepsy, beam balance ability, olfactory discrimination, social recognition, and spontaneous locomotor activity were assessed on days 19, 21, 23, 26, and 32, respectively. In cell culture, SA at 200, 600, and 1000 µg/mL significantly decreased ROS levels in H2O2-treated SK-N-SH cells. MPTP-treated C57BL/6 mice showed a significant change in all parameters tested when compared to the control group. Pretreatment and concurrent treatment with 200 mg/kg/day SA could antagonize the motor and cognitive function deficits induced by MPTP. The results show that SA possesses anti-Parkinson effects in MPTP-treated C57BL/6 mice and that reduction in ROS levels might be one of the mechanisms.

Download Full-text

Long non-coding RNA NEAT1 mediates MPTP/MPP+-induced apoptosis via regulating the miR-124/KLF4 axis in Parkinson’s disease

Open Life Sciences ◽

10.1515/biol-2020-0069 ◽

2020 ◽

Vol 15 (1) ◽

pp. 665-676

Author(s):

Jiyao Liu ◽

Defang Liu ◽

Bo Zhao ◽

Cunwei Jia ◽

Yunli Lv ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Viability ◽

Th Cells ◽

Expression Levels ◽

Non Coding Rna ◽

Apoptotic Protein ◽

Induced Apoptosis ◽

Related Proteins

AbstractAccumulating evidence suggests that dysregulation of long non-coding RNAs is closely associated with various human diseases, including Parkinson’s disease (PD). However, the role of nuclear-enriched abundant transcript 1 (NEAT1) in the PD process remains unclear. The number of TH+ cells was reduced, and the expression levels of NEAT1 and Krüppel-like factor 4 (KLF4) were increased in the midbrain of MPTP-HCl-treated mice. In addition, the expression of cleaved-caspase-3 (cleaved-casp-3) and Bax (apoptosis-related proteins) was increased, while the expression of Bcl-2 (anti-apoptotic protein) was reduced in MPTP-HCl-treated mice. The expression levels of NEAT1 and KLF4 were increased in MPP+-treated SH-SY5Y cells. Knockdown of NEAT1 promoted cell viability and decreased apoptosis in MPP+-treated SH-SY5Y cells, which could be reversed by upregulating KLF4. KLF4 was verified as a direct target of miR-124, and miR-124 could particularly bind to NEAT1. Downregulation of NEAT1 significantly increased cell viability and decreased apoptosis by regulating miR-124 expression in MPP+-treated SH-SY5Y cells. Additionally, interference of NEAT1 increased the number of TH+ cells and miR-124 expression, while reduced apoptosis and expression of KLF4 in vivo. NEAT1 knockdown increased cell viability and suppressed apoptosis in PD via regulating the miR-124/KLF4 axis, providing a promising avenue for the treatment of PD.

Download Full-text

The Effect of Sodium Metabisulphite on Apoptosis in the Experimental Model of Parkinson’s Disease

Current Nutrition & Food Science ◽

10.2174/1573401314666180503153444 ◽

2020 ◽

Vol 16 (3) ◽

pp. 296-305

Author(s):

Ayse Ozkan ◽

Hande Parlak ◽

Aysel Agar ◽

Özlem Özsoy ◽

Gamze Tanriover ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Tyrosine Hydroxylase ◽

Experimental Model ◽

Caspase 3 ◽

Control Group ◽

Activity Levels ◽

Control Groups ◽

Sodium Metabisulphite ◽

Apoptotic Protein

Background: The aim of this study was to investigate the mechanisms underlying possible toxic effects of sulphite on neurodegeneration. Methods: Male Wistar rats were assigned to each of the four groups: Control (Control), Sulphite-treated (Sulphite), 6-hydroxydopamine (6-OHDA)-injected (6-OHDA), and sulphite-treated and 6-OHDA-injected (6-OHDA+Sulphite). Sodium metabisulphite was administered orally by gavage at a dose of 100 mg/kg/day for 45 days. Experimental PD was created stereotactically via the unilateral infusion of 6-OHDA into the medial forebrain bundle (MFB). Rotarod performances, plasma S-sulfonate levels, caspase-3 activities, Bax and Bcl-2 levels, tyrosine hydroxylase (TH) and cleaved caspase-3 double staining were investigated. Results: The rotarod test showed that the 6-OHDA-injected animals exhibited shorter time on the rod mile compared to the control group; however, there was no difference between 6-OHDA and 6-OHDA+Sulphite groups. Plasma levels of S-sulfonate in Sulphite and 6-OHDA+ Sulphite groups increased in contrast to their corresponding control groups. Caspase-3 enzyme activity increased in the 6-OHDA group whereas it did not in control. However, sulphite treatment did not affect these activity levels. Anti-apoptotic protein Bcl-2 concentration decreased, but the concentration of pro-apoptotic protein Bax increased in the 6-OHDA group compared to the control group. The expression of caspase-3 increased, while the number of tyrosine hydroxylase (TH)-positive neurons decreased in 6-OHDA group as compared to the control groups. However, sulphite treatment had no effect on these parameters. Conclusion: Sulphite is not a potentially aggravating factor for the activity of caspase-3 in a 6- OHDA-induced experimental model of Parkinson’s disease.

Download Full-text

Protective Effect of Compound Formula Rehmannia against Neurotoxicity and Apoptosis Induced by α-Syn in In Vivo and In Vitro Models of Parkinson’s Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5201912 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Long Teng ◽

Minchun Yang ◽

Xiaoqing Jin ◽

Lu Qian ◽

Weijia Yang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Effect ◽

Cell Viability ◽

Cell Apoptosis ◽

In Vitro Models ◽

Western Blot Assay ◽

Rotation Numbers

The present study aimed to investigate the protective effect of compound formula Rehmannia (CFR) against the development of Parkinson’s disease (PD). After the in vivo and in vitro models of PD were established with overexpression α-syn induced, CFR was administrated into the PD model rats for 6 weeks or SK-N-SH cells with coincubation for 48 h. Apomorphine-induced rotation test, CCK8 assay, TUNEL assay, immunofluorescence staining, and western blot assay were performed to evaluate the behavioral changes, cell viability, cell apoptosis, α-syn, GSK-3β, P-GSK-3β (Ser9), P-GSK-3β (Tyr216), and β-catenin expression in PD rats or SK-N-SH cells. PD rat behavior results showed that the rotation numbers were significantly decreased in the CFR treatment group comparing with the AAV-α-syn PD model group. The cell viability suppressed by H2O2 and α-syn in SK-N-SH model cells was also significantly improved with CFR administration. Cell apoptosis and α-syn overexpression observed in PD rats and SK-N-SH cells were also inhibited by CFR treatment. Furthermore, the protein expression of α-syn, GSK-3β, P-GSK-3β (Ser9), P-GSK-3β (Tyr216), and β-catenin in in vivo and in vitro was also significantly regulated by CFR. The present study suggested that CFR may be considered as a potential neuroprotective agent against PD, and this application will require further investigation.

Download Full-text

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Frontiers in Neuroscience ◽

10.3389/fnins.2021.631501 ◽

2021 ◽

Vol 15 ◽

Author(s):

ZhengHu Xu ◽

Dongfeng Yang ◽

Xiaojing Huang ◽

Huai Huang

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Viability ◽

Cell Model ◽

Astragaloside Iv ◽

Stat3 Pathway ◽

Apoptosis Rate ◽

6 Hydroxydopamine ◽

And Oxidative Stress

ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and MethodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

Download Full-text

Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00341-0 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Hamdy N. El-Tallawy ◽

Tahia H. Saleem ◽

Wafaa M. Farghaly ◽

Heba Mohamed Saad Eldien ◽

Ashraf Khodaery ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Case Control Study ◽

Case Control ◽

Control Group ◽

Motor Symptoms ◽

And Control ◽

Non Motor Symptoms ◽

Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

Download Full-text

Donepezil for mild cognitive impairment in Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-84243-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyoungwon Baik ◽

Seon Myeong Kim ◽

Jin Ho Jung ◽

Yang Hyun Lee ◽

Seok Jong Chung ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Treatment Group ◽

Outcome Measures ◽

Rating Scale ◽

Secondary Outcome ◽

Control Group ◽

Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

Download Full-text

Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

Scientific Reports ◽

10.1038/s41598-021-92701-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pusheng Quan ◽

Kai Wang ◽

Shi Yan ◽

Shirong Wen ◽

Chengqun Wei ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Drug Target ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Control Group ◽

Drug Candidates ◽

Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

Download Full-text

Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽

10.3390/medicina57040314 ◽

2021 ◽

Vol 57 (4) ◽

pp. 314

Author(s):

Aida Arroyo-Ferrer ◽

Francisco José Sánchez-Cuesta ◽

Yeray González-Zamorano ◽

María Dolores del Castillo ◽

Carolina Sastre-Barrios ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Therapy ◽

Cognitive Processing ◽

Processing Speed ◽

Cognitive Rehabilitation ◽

Neurodegenerative Disorder ◽

Control Group ◽

Motor Symptoms ◽

The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

Download Full-text