scholarly journals miR-185 and SEPT5 Genes May Contribute to Parkinson’s Disease Pathophysiology

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Arman Rahimmi ◽  
Ilaria Peluso ◽  
Aref Rajabi ◽  
Kambiz Hassanzadeh
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Chromosomal Location ◽  
Gene Expression Pattern ◽  
Control Group ◽  
Significant Difference

There are still unknown mechanisms involved in the development of Parkinson’s disease (PD), which elucidating them can assist in developing efficient therapies. Recently, studies showed that genes located on the human chromosomal location 22q11.2 might be involved in the development of PD. Therefore, the present study was designed to evaluate the role of two genes located on the chromosomal location (miR-185 and SEPT5), which were the most probable candidates based on our bibliography. In vivo and in vitro models of PD were developed using male Wistar rats and SHSY-5Y cell line, respectively. The expression levels of miR-185, SEPT5, LRRK2, and PARK2 genes were measured at a mRNA level in dopaminergic areas of rats’ brains and SHSY-5Y cells using the SYBR Green Real-Time PCR Method. Additionally, the effect of inhibition on the genes or their products on cell viability and gene expression pattern in SHSY-5Y cells was investigated. The level of miR-185 gene expression was significantly decreased in the substantia nigra (SN) and striatum (ST) of the rotenone-treated group (control group) compared to the healthy normal group (P<0.05). In addition, there was a significant difference in the expression of SEPT5 gene (P<0.05) in the substantia nigra between two studied groups. The results of an in vitro study showed no significant change in the expression of the genes; however, the inhibition on miR-185 gene expression led to the increase in LRRK2 gene expression in SHSY-5Y cells. The inhibition on LRRK2 protein also decreased the cellular toxicity effect of rotenone on SHSY-5Y cells. The results suggested the protective role of miR-185 gene in preventing the development of PD.

Parkinsonism-like disease induced by rotenone in rats: Treatment role of curcumin, dopamine agonist and adenosine A2A receptor antagonist

2021 ◽  
Vol 14 ◽  
Author(s):  
Asmaa Fathy Aboul Naser ◽  
Wessam Magdi Aziz ◽  
Yomna Rashad Ahmed ◽  
Wagdy Khalil Bassaly Khalil ◽  
Manal Abdel Aziz Hamed
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Mediator ◽  
Adenosine A2a Receptor ◽  
Control Group ◽  
A2a Receptor ◽  
Adenosine A2a

Background: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide. Methods: Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson’s disease (PD) induced by rotenone in rats and comparativelyrelatively compared with our previous study on mice model. Results: Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compare with the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats regarding to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding to oxidative stress and energetic indices. Conclusion: Curcumin succeeded to attenuate the severe effects of Parkinson’s disease in rat model and can be consider as a potential dietary supplement. Adenosine A2AR antagonist has almost the same pattern of improvement as Sinemet® and may be considered as a promising therapy against PD. By comparing the role of animal species in response to PD symptoms and treatments, our previous report on mice explore the response of mice to rotenone toxicity than rats, while rats showed higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

scholarly journals Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model

2021 ◽  
Author(s):  
Hossein Mostafavi ◽  
Meysam Forouzandeh ◽  
Mohammad Reza Bigdeli ◽  
Samad Nadri ◽  
Mehdi Eskandari
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Control Group ◽  
Mrna Levels ◽  
Significant Difference ◽  
Free Cells

Abstract Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.

scholarly journals Donepezil for mild cognitive impairment in Parkinson’s disease

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.

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 79 ◽  
Author(s):  
Sergejs Isajevs ◽  
Darja Isajeva ◽  
Ulrika Beitnere ◽  
Baiba Jansone ◽  
Ivars Kalvinsh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Substantia Nigra ◽  
Rat Model ◽  
Control Group ◽  
Western Blot Assay ◽  
Neural Cell Adhesion ◽  
6 Hydroxydopamine ◽  
Cardioprotective Drug

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM). Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay. Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values. Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.

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 The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Victor Blokhin ◽  
Maria Shupik ◽  
Ulyana Gutner ◽  
Ekaterina Pavlova ◽  
Albert T. Lebedev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sphingolipid Metabolism ◽  
Nigrostriatal System ◽  
Dopaminergic Cell ◽  
Metabolism Enzymes ◽  
Clinical Stages ◽  
Sphingosine 1 Phosphate

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

scholarly journals Substantia nigra ferric overload and neuromelanin loss in Parkinson's disease measured with 7T MRI

2021 ◽  
Author(s):  
Catarina Rua ◽  
Claire O'Callaghan ◽  
Rong Ye ◽  
Frank Hubert Hezemans ◽  
Luca Passamonti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Resolution ◽  
Substantia Nigra ◽  
Clinical Severity ◽  
7 Tesla ◽  
Control Group ◽  
Healthy Controls ◽  
Iron Loading ◽  
Weighted Sequence

Background: Vulnerability of the substantia nigra dopaminergic neurons in Parkinson's disease is associated with ferric overload, leading to neurodegeneration with cognitive and motor decline. Here, we quantify iron and neuromelanin-related markers in vivo using ultra-high field 7-Tesla MRI, and examine the clinical correlates of these imaging assessments. Methods: Twenty-five people with mild-to-moderate Parkinson's disease and twenty-six healthy controls underwent high-resolution imaging at 7-Tesla with a T2*-weighted sequence (measuring susceptibility-χ and R2*, sensitive to iron) and a magnetization transfer-weighted sequence (MT-w, sensitive to neuromelanin). From an independent control group (N=29), we created study-specific regions-of-interest for five neuromelanin- and/or iron-rich subregions within the substantia nigra. Mean R2*, susceptibility-χ and their ratio, as well as the MT-w contrast-to-noise ratio (MT-CNR) were extracted from these regions and compared between groups. We then tested the relationships between these imaging metrics and clinical severity. Results: People with Parkinson's disease showed a significant ~50% reduction in MT-CNR compared to healthy controls. They also showed a 1.2-fold increase in ferric iron loading (elevation of the ΔR2*/Δχ ratio from 0.19±0.058ms/ppm to 0.22±0.059ms/ppm) in an area of the substantia nigra identified as having both high neuromelanin and susceptibility MRI signal in healthy controls. In this region, the ferric-to-ferrous iron loading was associated with disease duration (β=0.0072, pFDR=0.048) and cognitive impairment (β=-0.0115, pFDR=0.048). Conclusions: T2*-weighted and MT-weighted high-resolution 7T imaging markers identified neurochemical consequences of Parkinson's disease, in overlapping but not-identical regions. These changes correlated with non-motor symptoms.

scholarly journals The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ovidiu-Dumitru Ilie ◽  
Emanuela Paduraru ◽  
Madalina-Andreea Robea ◽  
Ioana-Miruna Balmus ◽  
Roxana Jijie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Locomotor Activity ◽  
Prolonged Exposure ◽  
Bifidobacterium Longum ◽  
The Body ◽  
The Other ◽  
Control Group

Background. As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson’s disease. The latest reports have indeed revealed that rotenone promotes Parkinson’s in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. Results. There were no statistically significant differences following the analysis of their social interaction and locomotor tests ( p > 0.05 ). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval ( p < 0.05 ). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics ( p > 0.05 ), relevant changes have been observed between the analyzed groups ( p < 0.05 and p < 0.005 , respectively). On the other hand, significant differences ( p < 0.05 ) have been observed for MDA when we analyzed the data between the control group and the other three groups. Conclusions. Our results suggest that rotenone can be successfully used to trigger Parkinson’s disease-related symptomatology in zebrafish.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in Parkinson’s disease and atypical parkinsonian syndromes

2021 ◽  
Author(s):  
Michaela Kaiserova ◽  
Monika Chudackova ◽  
Hana Prikrylova Vranova ◽  
Katerina Mensikova ◽  
Anetta Kastelikova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Statistical Significance ◽  
Corticobasal Degeneration ◽  
Control Group ◽  
Csf Biomarkers ◽  
Parkinsonian Syndromes ◽  
Significant Difference ◽  
Hydroxyindoleacetic Acid

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).

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