scholarly journals Aberrant expression of microRNA-132-3p and microRNA-146a-5p in Parkinson’s disease patients

2020 ◽  
Vol 15 (1) ◽  
pp. 647-653
Author(s):  
Yu Shu ◽  
Jinjun Qian ◽  
Chunyan Wang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Healthy Volunteers ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Quantitative Polymerase Chain Reaction ◽  
Serum Samples ◽  
Aberrant Expression ◽  
Braak Staging ◽  
Age Related

AbstractParkinson’s disease (PD) is an age-related neurodegenerative disorder which is assessed based on the motor symptoms. A number of microRNAs (miRNAs) are dysregulated and involved in the pathogenesis or development of PD. However, no confirmed markers are used for the early detection of PD. The present study aimed to elucidate the potential two miRNAs (miR-132-3p and miR-146-5p) as novel markers for early PD diagnosis. In the present study, the expression levels of miR-132-3p and miR-146-5p in serum samples from 82 patients with PD and 44 healthy volunteers were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, the correlation analysis was performed between aberrant miRNAs and Braak staging, Part V of the Unified Parkinson’s Disease Rating Scale (UPDRS-V; the modified Hoehn and Yahr staging of PD) and Part III of the UPDRS-III. Subsequently, the receiver–operating characteristic (ROC) curve results of miR-132-3p and miR-146-5p from healthy volunteers for PD prediction and from severe PD patients were assessed. From the results it was observed that miR-132-3p and miR-146a-5p expressions were significantly decreased in the serum samples of patients with PD compared to those in the healthy volunteers. Moreover, the expressions of miR-132-3p and miR-146a-5p showed a dramatic decrease in severe PD patients as compared to the normal PD patients. Meanwhile, miR-132-3p and miR-146-5p expressions were negatively correlated with Braak staging (r = −0.45, P < 0.0001; r = −0.51, P < 0.0001), UPDRS-III (r = −0.55, P < 0.0001; r = −0.51, P < 0.0001) and UPDRS-V scores (r = − 0.46, P < 0.0001; r = −0.45, P < 0.0001) in PD patients. The area under the curve (AUC) results of miR-132-3p and miR-146a-5p in discriminating PD patients from the healthy controls were 0.7325 (95% CI = 0.6400–0.8251) and 0.7295 (95% CI = 0.3658–0.8232). Moreover, the AUC results of miR-132-3p and miR-146-5p concerning discriminating severe PD patients from normal PD patients were 0.8175 (95% CI = 0.7229–0.9121) and 0.7921 (95% CI = 0.6937–0.8905). In other words, both miR-132-3p and miR-146a-5p may function as promising biomarkers for early diagnosis of PD.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

scholarly journals Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3459 ◽  
Author(s):  
Sandra Barata-Antunes ◽  
Fábio G. Teixeira ◽  
Bárbara Mendes-Pinheiro ◽  
Ana V. Domingues ◽  
Helena Vilaça-Faria ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Welfare ◽  
Neurodegenerative Disorder ◽  
Negative Impact ◽  
Substantia Nigra Pars Compacta ◽  
Nigrostriatal Pathway ◽  
Aged Rats ◽  
Age Related ◽  
The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

scholarly journals Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson’s Disease Models

2019 ◽  
Vol 20 (20) ◽  
pp. 5208 ◽  
Author(s):  
Bongki Cho ◽  
Taeyun Kim ◽  
Yu-Jin Huh ◽  
Jaemin Lee ◽  
Yun-Il Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Ubiquitin Proteasome System ◽  
Natural Compounds ◽  
Cellular Damage ◽  
Pathophysiological Mechanism ◽  
Neuroprotective Effects ◽  
Age Related

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD.

scholarly journals A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Shankar J. Chinta ◽  
Subramanian Rajagopalan ◽  
Abirami Ganesan ◽  
Julie K. Andersen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Nitrosative Stress ◽  
Neurodegenerative Disorder ◽  
Oxidative And Nitrosative Stress ◽  
Prolyl Hydroxylases ◽  
Age Related

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB’s ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cellsin vitroin conjunction with reduced ROS production and activation of NFκB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NFκB activity and subsequent NO induction.In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB’s neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1.

scholarly journals Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

2015 ◽  
Vol 51 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Débora Dalla Vecchia ◽  
Marissa Giovanna Schamne ◽  
Marcelo Machado Ferro ◽  
Ana Flávia Chaves dos Santos ◽  
Camila Lupepsa Latyki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Hypericum Perforatum ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Turning Behavior ◽  
Age Related ◽  
Lesion Side ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

CO-MORBIDITY BURDEN IN PARKINSON'S DISEASE AND MATCHED CONTROLS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.86-e4
Author(s):  
Hannah Goddard ◽  
Angus Macleod ◽  
Carl Counsell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Predictive Ability ◽  
Morbidity Burden ◽  
Co Morbidity ◽  
Significant Difference ◽  
Morbidity Index

BackgroundIdiopathic Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. The overall co-morbidity burden associated with PD is unclear, but may be important to adjust for when predicting prognosis or comparing cases and controls.Aims ▸ To determine how best to assess overall co-morbidity in PD▸ To compare PD co-morbidity burden to that of age- and sex-matched controlsMethodsData from an incident, community-based cohort of 205 patients with PD and 148 age-, sex- and GP-matched controls (the PINE study) were used. The intra- and inter-rater reliability and mortality predictive ability of three co-morbidity scales (the Charlson Co-Morbidity Index, the Cumulative Illness Rating Scale and a disease count) were evaluated. The co-morbidity burden of cases and controls was compared at baseline and over 5 years of follow-up.Results and conclusionsThe Charlson Co-Morbidity Index was more reliable for use in PD and was the only scale that was independently predictive of mortality (hazard ratio=1.20, [95% CI 1.07–1.34]). There was no significant difference between cases and controls at baseline (p=0.20). Charlson Co-Morbidity Index scores increased over time. This increase was greater in patients with PD than controls and greater in patients and controls who died earlier.

Tremor in Parkinson’s disease and serotonergic dysfunction

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 601-605 ◽  
Author(s):  
M. Doder ◽  
E. A. Rabiner ◽  
N. Turjanski ◽  
A. J. Lees ◽  
D. J. Brooks
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Healthy Volunteers ◽  
Rating Scale ◽  
Indirect Evidence ◽  
Binding Potential ◽  
Reference Tissue ◽  
Parkinsonian Tremor ◽  
System Integrity ◽  
Way 100635

Background: The pathophysiologic mechanisms underlying parkinsonian tremor remain unclear. The response to dopaminergic treatment is variable and nondopaminergic mechanisms may play a role in tremor generation. Midbrain raphe 5-HT1A binding provides a functional measure of serotonergic system integrity. With PET, the aim of this study was to examine regional cerebral 11C-WAY 100635 binding to 5-HT1A receptors in patients with PD and to correlate it with severity of tremor.Methods:11C-WAY 100635 PET was performed on 23 patients with PD and eight age-matched healthy volunteers. Brain 5-HT1A receptor binding was computed using compartmental modeling with a cerebellar reference tissue input function.Results: The authors found mean 27% reduction in the midbrain raphe 5-HT1A binding potential in patients with PD compared to healthy volunteers (p < 0.001). They also showed that Unified Parkinson’s Disease Rating Scale composite tremor scores, but not rigidity or bradykinesia, correlate with 5-HT1A binding in the raphe (p < 0.01).Conclusions: These findings support previous indirect evidence that serotonergic neurotransmission is decreased in PD in vivo. The authors hypothesize that the reduction in raphe 5-HT1A binding represents receptor dysfunction or loss of cell bodies due to Lewy body degeneration in PD, or both. An association between 5-HT1A receptor availability in the raphe and severity of parkinsonian tremor was also found.

scholarly journals Functional and Cognitive Improvement After an Intensive Inpatient Multidisciplinary Rehabilitation Program in Mild to Severe Parkinson's Disease: A Retrospective and Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Meloni ◽  
Francesca Lea Saibene ◽  
Sonia Di Tella ◽  
Monica Di Cesare ◽  
Francesca Borgnis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Observational Study ◽  
Functional Disability ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Rehabilitation Program ◽  
Semantic Fluency ◽  
Multidisciplinary Rehabilitation ◽  
Cognitive Improvement

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor (resting tremor, rigidity, bradykinesia, postural instability, and gait disturbances) and nonmotor symptoms (cognitive, neuropsychiatric, and autonomic problems). In recent years, several studies demonstrated that neurorehabilitation therapy is an effective treatment in addition to pharmacological personalized interventions in persons with PD (PwPD). The main aim of this study was to explore the short-term changes in functional, cognitive, and geriatric domains after a multidimensional rehabilitation program in PwPD (as primary condition) in mild–moderate (M-Ms) to severe (Ss) stages. Our second aim was to compare the effects of multidimensional rehabilitation in M-Ms versus Ss of PD. Twenty-four PwPD in M-Ms to Ss [age (mean ± SD) = 76.25 ± 9.42 years; male/female = 10/14; Hoehn and Yahr (median; IQR) = 4.00; 1.75] were included in a retrospective, observational study. Motor, cognitive, functional, and neuropsychiatric aspects were collected in admission (T0) and in discharge (T1). PwPD were involved in a person-tailored (to individual's needs), inpatient, intensive (5–7 days per week), multidisciplinary (combining cognitive, physical, occupational, and speech therapies), comprehensive, and rehabilitative program. According to Movement Disorders Society Unified Parkinson's Disease Rating Scale III cutoff, PwPD were classified in M-Ms or Ss (M-Ms ≤59; Ss &gt;59); 87.50% of our sample reported significant reduction of functional disability at Barthel Index (p &lt; 0.001). A significant improvement in Token test (p = 0.021), semantic fluency (p = 0.036), Rey's Figure-Copy (p &lt; 0.001), and Raven's Colored Progressive Matrices (p = 0.004) was observed. The pain intensity perception (p &lt; 0.001) and the risk of developing pressure ulcers (p &lt; 0.001) as assessed, respectively, by the Numeric Rating Scale and by the Norton Scale were improved. With regard to the second aim, in M-Ms group, we found a positive correlation between the number of neuromotor sessions and the change in functional disability and language comprehension; in the Ss group, on the other hand, despite a higher number of hospitalization days, the total number of completed sessions was positively associated with the change in visuoconstructional abilities. Our findings suggest that an intensive, inpatient, and multidisciplinary rehabilitation program may improve functional abilities, some strategic cognitive functions, and geriatric aspects in PwPD with mild–moderate motor impairment.

scholarly journals Outcome of Deep Brain Stimulation (DBS) for the Treatment of Parkinson’s Disease in Terms of Improvement in MDS-UPDRS Scale Over 5 Years

2021 ◽  
Vol 24 (4) ◽  
pp. 305-314
Author(s):  
Khalid Mahmood ◽  
Omair Afzal Ali ◽  
Adeeb-ul- Hassan ◽  
Imran Ali
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Disease Rating ◽  
The Mean ◽  
Updrs Part ◽  
Deep Brain

Background & Objective:  Parkinson’s disease (PD) is the second most common Neurodegenerative disorder after Alzheimer’s disease. There are several surgical procedures for advanced PD, but amongst all deep brain stimulation has proven to be safest and effective. The objective of this study was to see the outcome of DBS for the treatment of PD in terms of improvement in MDS UPDRS over 5 years. Material and Methods:  44 patients were included in study from Oct 2014 to Sep 2019. History, examination was carried out, and preoperative MDS-UPDRS (Movement Disorder Society Unified Parkinson’s Disease Rating Scale) was recorded. Postoperative improvement in MDS-UPDRS score was assessed at first Programming, 2nd week, and 6th week and at 3rd month. Results:  At baseline the mean, the MDS – UPDRS (Part-I) score was 14.20 ± 0.61 and at the end of 3rd month, the mean score was 11.18 ± 0.47 respectively. At baseline the mean, the MDS – UPDRS (part-II) score was 18.99 ± 0.70 and at the end of 3rd month, the mean score was 13.01 ± 0.57, respectively. At baseline the mean, the MDS – UPDRS (part-III) score was 45.19 ± 0.90 and at the end of 3rd month, the mean score was 25.15 ± 1.20 respectively. At baseline the mean, the MDS – UPDRS (part-IV) score was 10.18 ± 0.87 and at the end of 3rd month, the mean score was 3.85 ± 1.03, respectively.  Conclusion:  The Deep Brain Stimulation (DBS) is safe and effective in the management of PD.

scholarly journals Predicting Longitudinal Disease Severity for Individuals with Parkinson’s Disease using Functional MRI and Machine Learning Prognostic Models

2020 ◽  
Author(s):  
Kevin P. Nguyen ◽  
Vyom Raval ◽  
Alex Treacher ◽  
Cooper Mellema ◽  
Frank Yu ◽  
...  
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Severity ◽  
Clinical Decision Making ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Clinical Severity ◽  
Predictive Values ◽  
Updrs Score

AbstractParkinson’s disease is the second most common neurodegenerative disorder and is characterized by the loss of ability to control voluntary movements. Predictive biomarkers of progression in Parkinson’s Disease are urgently needed to expedite the development of neuroprotective treatments and facilitate discussions about disease prognosis between clinicians and patients. Resting-state functional magnetic resonance imaging (rs-fMRI) shows promise in predicting progression, with derived measures, including regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF), having been previously been associated with current disease severity. In this work, ReHo and fALFF features from 82 Parkinson’s Disease subjects are used to train machine learning predictors of baseline clinical severity and progression at 1 year, 2 years, and 4 years follow-up as measured by the Movement Disorder Society Unified Depression Rating Scale (MDS-UPDRS) score. This is the first time that rs-fMRI and machine learning have been combined to predict future disease progression. The machine learning models explain up to 30.4% (R2 = 0.304) of the variance in baseline MDS-UPDRS scores, 55.8% (R2 = 0.558) of the variance in year 1 scores, and 47.1% (R2 = 0.471) of the variance in year 2 scores with high statistical significance (p < 0.0001). For distinguishing high- and low-progression individuals (MDS-UPDRS score above or below the median), the models achieve positive predictive values of up to 71% and negative predictive values of up to 84%. The models learn patterns of ReHo and fALFF measures that predict better and worse prognoses. Higher ReHo and fALFF in regions of the default motor network predicted lower current severity and lower future progression. The rs-fMRI features in the temporal lobe, limbic system, and motor cortex were also identified as predictors. These results present a potential neuroimaging biomarker that accurately predicts progression, which may be useful as a clinical decision-making tool and in future trials of neuroprotective treatments.

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