scholarly journals Reduced synaptic activity and dysregulated extracellular matrix pathways are common phenotypes in midbrain neurons derived from sporadic and mutation-associated Parkinson's disease patients

2022 ◽  
Author(s):  
Shani Stern ◽  
Shong Lau ◽  
Andreea Manole ◽  
Idan Rosh ◽  
Menahem Percia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Extracellular Matrix ◽  
Parkinson's Disease ◽  
Synaptic Activity ◽  
Cellular Models ◽  
Midbrain Neurons ◽  
Severe Reduction ◽  
Show Evidence ◽  
Induced Pluripotent ◽  
The Relationship

Several mutations that cause Parkinson's disease (PD) have been identified over the past decade. These account for 15-25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: Neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, shows pathways and mechanisms that are central and convergent to PD and suggests a strong involvement of the tetra-partite synapse in PD pathology.

Appendectomy Does Not Increase the Risk of Future Emergence of Parkinson’s Disease: A Meta-analysis

2021 ◽  
pp. 000313482198903
Author(s):  
Mitsuru Ishizuka ◽  
Norisuke Shibuya ◽  
Kazutoshi Takagi ◽  
Hiroyuki Hachiya ◽  
Kazuma Tago ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Significant Difference ◽  
The Cochrane Library ◽  
The Impact ◽  
The Relationship ◽  
Observation Period

Objective To explore the impact of appendectomy history on emergence of Parkinson’s disease (PD). Background Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial. Methods We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using I2 statistics. Results Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; P = .83; I2 = 87%). Conclusion This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.

scholarly journals Parkinson’s Disease and the COVID-19 Pandemic

2021 ◽  
pp. 1-14
Author(s):  
Conor Fearon ◽  
Alfonso Fasano
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Indirect Effects ◽  
Mortality Data ◽  
Contributing Factors ◽  
Scientific Rigor ◽  
The Impact ◽  
The Relationship ◽  
Non Motor Symptoms ◽  
Convincing Data

Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson’s disease (PD) have provided conflicting results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: ‘Parkinson’s disease’ and ‘parkinsonism’ combined with: ‘COVID-19’; ‘SARS-CoV-2’ and ‘coronavirus’. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.

Self-Perception of Voice and Swallowing Handicap in Parkinson’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Alice K. Silbergleit ◽  
Lonni Schultz ◽  
Kendra Hamilton ◽  
Peter A. LeWitt ◽  
Christos Sidiropoulos
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Self Perception ◽  
Functional Aspects ◽  
Dysphagia Handicap Index ◽  
Relationship Of ◽  
The Relationship

Background: Hypokinetic dysarthria and dysphagia are known features of Parkinson’s disease; however, self-perception of their handicapping effects on emotional, physical, and functional aspects of quality of life over disease duration is less understood. Objective: 1) Based upon patient self-perception, to determine the relationship of the handicapping effects of dysphagia and dysphonia with time since diagnosis in individuals with Parkinson’s disease; 2)To determine if there is a relationship between voice and swallowing handicap throughout the course of Parkinson’s disease. Method: 277 subjects completed the Dysphagia Handicap Index and the Voice Handicap Index. Subjects were divided into three groups based on disease duration: 0–4 years, 5–9 years, and 10 + years. Results: Subjects in the longer duration group identified significantly greater perceptions of voice and swallowing handicap compared to the shorter duration groups. There was a significant positive correlation between the DHI and VHI. Conclusion: Self-perception of swallowing and voice handicap in Parkinson’s disease are associated with later stages of disease and progress in a linear fashion. Self-perception of voice and swallowing handicap parallel each other throughout disease progression in Parkinson’s disease. Individuals may be able to compensate for changes in voice and swallowing early while sensory perceptual feedback is intact. Results support early targeted questioning of patient self-perception of voice and swallowing handicap as identification of one problem indicates awareness of the other, thus creating an opportunity for early treatment and maintenance of swallowing and communication quality of life for as long as possible.

1.158 The relationship between Parkinson's disease and nutritional status

2007 ◽  
Vol 13 ◽  
pp. S48-S49
Author(s):  
X. Tan ◽  
Y. Luo ◽  
J. Pan ◽  
P.-Q. Wang ◽  
B. Huan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nutritional Status ◽  
The Relationship

scholarly journals Alteration in the Cerebrospinal Fluid Lipidome in Parkinson’s Disease: A Post-Mortem Pilot Study

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 491
Author(s):  
Joaquín Fernández-Irigoyen ◽  
Paz Cartas-Cejudo ◽  
Marta Iruarrizaga-Lejarreta ◽  
Enrique Santamaría
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Ultra Performance Liquid Chromatography ◽  
Small Population ◽  
Control Group ◽  
Post Mortem ◽  
Cellular Models ◽  
Flight Mass Spectrometry ◽  
Lipid Species

Lipid metabolism is clearly associated to Parkinson’s disease (PD). Although lipid homeostasis has been widely studied in multiple animal and cellular models, as well as in blood derived from PD individuals, the cerebrospinal fluid (CSF) lipidomic profile in PD remains largely unexplored. In this study, we characterized the post-mortem CSF lipidomic imbalance between neurologically intact controls (n = 10) and PD subjects (n = 20). The combination of dual extraction with ultra-performance liquid chromatography-electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-qToF-MS/MS) allowed for the monitoring of 257 lipid species across all samples. Complementary multivariate and univariate data analysis identified that glycerolipids (mono-, di-, and triacylglycerides), saturated and mono/polyunsaturated fatty acids, primary fatty amides, glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines), sphingolipids (ceramides, sphingomyelins), N-acylethanolamines and sterol lipids (cholesteryl esters, steroids) were significantly increased in the CSF of PD compared to the control group. Interestingly, CSF lipid dyshomeostasis differed depending on neuropathological staging and disease duration. These results, despite the limitation of being obtained in a small population, suggest extensive CSF lipid remodeling in PD, shedding new light on the deployment of CSF lipidomics as a promising tool to identify potential lipid markers as well as discriminatory lipid species between PD and other atypical parkinsonisms.

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