scholarly journals Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson’s Disease Patients

2019 ◽  
Vol 20 (3) ◽  
pp. 771 ◽  
Author(s):  
Carmen Vida ◽  
Hikaru Kobayashi ◽  
Antonio Garrido ◽  
Irene Martínez de Toda ◽  
Eva Carro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Whole Blood ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Lymphoproliferative Response ◽  
Healthy Elderly ◽  
Age Related ◽  
Whole Blood Cells

In Parkinson’s Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based on a chronic-oxidative stress situation, is involved in the rate of aging. We analyzed several functions in isolated peripheral blood neutrophils and mononuclear cells from PD stage 2 patients, and compared the results to those in healthy elderly and adult controls. Several oxidative stress and damage parameters were studied in whole blood cells. The results showed an impairment of the lymphoproliferative response in stimulated conditions in the PD patients compared with age-matched controls, who also showed typical immunosenescence in comparison with adult individuals. Higher oxidative stress and damage were observed in whole blood cells from PD patients (lower glutathione peroxidase activity, and higher oxidized glutathione and malondialdehyde contents). Our results suggest an accelerated immunosenescence in PD stage 2, and that several of the parameters studied could be appropriate peripheral biomarkers in the early stages of PD.

Age-Related Accelerated Tapping Response in Healthy Population

2003 ◽  
Vol 96 (1) ◽  
pp. 227-235 ◽  
Author(s):  
Anat Scheiman Elazary ◽  
Hagai Bergman ◽  
Revital Attia ◽  
Hilla Ben-Pazi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Elderly Subjects ◽  
Healthy Population ◽  
Healthy Elderly ◽  
Age Related ◽  
Different Types ◽  
Finger Tapping Test ◽  
Healthy Elderly People ◽  
Abnormal Motor

Different types of rapid tapping responses were described in the finger-tapping test. The “Hastening phenomenon” was described as an abnormal motor response in patients with Parkinson's disease. Accelerated tapping has been shown in a healthy elderly sample. It is not clear whether accelerated tapping relates to the hastening phenomenon or characterizes normal aging. We hypothesized that this sample of 21 healthy elderly people showed increased accelerated tapping but not hastening phenomenon. To assess this hypothesis, 20 healthy young and 21 elderly subjects performed a tapping test, requiring responses from 1 to 6 Hz. The healthy elderly sample showed increased accelerated tapping but not increased “hastening phenomenon.” We conclude that Accelerated tapping may represent age-related motor processes unlike the hastening phenomenon characterizing Parkinson's disease.

scholarly journals DNA Methylation and Expression Profiles of Whole Blood in Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrienne R. Henderson ◽  
Qi Wang ◽  
Bessie Meechoovet ◽  
Ashley L. Siniard ◽  
Marcus Naymik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Whole Blood ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Motor Deficits ◽  
Age Related

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non-invasively detectable in blood as potential markers of disease. We performed comparative analyses of the methylome and transcriptome in blood from PD patients and matched controls. Our aim was to characterize DNA methylation and gene expression patterns in whole blood from PD patients as a foundational step toward the future goal of identifying molecular markers that could predict, accurately diagnose, or track the progression of PD. We found that differentially expressed genes (DEGs) were involved in the processes of transcription and mitochondrial function and that PD methylation profiles were readily distinguishable from healthy controls, even in whole-blood DNA samples. Differentially methylated regions (DMRs) were functionally varied, including near transcription factor nuclear transcription factor Y subunit alpha (NFYA), receptor tyrosine kinase DDR1, RING finger ubiquitin ligase (RNF5), acetyltransferase AGPAT1, and vault RNA VTRNA2-1. Expression quantitative trait methylation sites were found at long non-coding RNA PAX8-AS1 and transcription regulator ZFP57 among others. Functional epigenetic modules were highlighted by IL18R1, PTPRC, and ITGB2. We identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood. Our combined analyses extended what we learned from the DEG or DMR results alone. These studies provide a foundation to support the characterization of larger sample cohorts, with the goal of building a thorough, accurate, and non-invasive molecular PD biomarker.

Neuroprotective effect of agmatine (decarboxylated l-arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson’s disease

2018 ◽  
Vol 38 (2) ◽  
pp. 173-184 ◽  
Author(s):  
EK El-Sayed ◽  
AAE Ahmed ◽  
EM El Morsy ◽  
S Nofal
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Sprague Dawley ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Sprague Dawley Rats

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer’s disease, characterized by loss of dopaminergic neurons in substantia nigra pars compacta, accompanied by motor and nonmotor symptoms. The neuropathological hallmarks of PD are well reported, but the etiology of the disease is still undefined; several studies assume that oxidative stress, mitochondrial defects, and neuroinflammation play vital roles in the progress of the disease. The current study was established to investigate the neuroprotective effect of agmatine on a rotenone (ROT)-induced experimental model of PD. Adult male Sprague Dawley rats were subcutaneously injected with ROT at a dose of 2 mg/kg body weight for 35 days. Agmatine was injected intraperitoneally at 50 and 100 mg/kg body weight, 1 h prior to ROT administration. ROT-treated rats that received agmatine showed better performance on beam walking and an elevated number of rears within the cylinder test. In addition, agmatine reduced midbrain malondialdehyde as an indication of lipid peroxidation, pro-inflammatory cytokines including tumor necrosis factor alpha and interleukin-1β, and glial fibrillary acidic protein. Moreover, agmatine was responsible for preventing loss of tyrosine hydroxylase-positive neurons. In conclusion, our study showed that agmatine possesses a dose-dependent neuroprotective effect through its antioxidant and anti-inflammatory activities. These findings need further clinical investigations of agmatine as a promising neuroprotective agent for the future treatment of PD.

scholarly journals PET Studies of Net Blood—Brain Clearance of FDOPA to Human Brain: Age-Dependent Decline of [18F]Fluorodopamine Storage Capacity

2005 ◽  
Vol 25 (7) ◽  
pp. 807-819 ◽  
Author(s):  
Yoshitaka Kumakura ◽  
Ingo Vernaleken ◽  
Gerhard Gründer ◽  
Peter Bartenstein ◽  
Albert Gjedde ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Storage Capacity ◽  
Compartmental Analysis ◽  
Graphical Analysis ◽  
Negative Bias ◽  
Precursor Pool ◽  
Healthy Elderly ◽  
Age Related ◽  
The Brain

Conventional methods for the graphical analysis of 6-[18F]fluorodopa (FDOPA)/positron emission tomography (PET) recordings ( Kappin) may be prone to negative bias because of oversubtraction of the precursor pool in the region of interest, and because of diffusion of decarboxylated FDOPA metabolites from the brain. These effects may reduce the sensitivity of FDOPA/PET for the detection of age-related changes in dopamine innervations. To test for these biasing effects, we have used a constrained compartmental analysis to calculate the brain concentrations of the plasma metabolite 3- O-methyl-FDOPA (OMFD) during 120 mins of FDOPA circulation in healthy young, healthy elderly, and Parkinson's disease subjects. Calculated brain OMFD concentrations were subtracted frame-by-frame from the dynamic PET recordings, and maps of the FDOPA net influx to brain were calculated assuming irreversible trapping ( Kapp). Comparison of Kappin and Kapp maps revealed a global negative bias in the conventional estimates of FDOPA clearance. The present OMFD subtraction method revealed curvature in plots of Kapp at early times, making possible the calculation of the corrected net influx ( K) and also the rate constant for diffusion of decarboxylated metabolites from the brain ( kloss). The effective distribution volume (EDV2; K/ kloss) for FDOPA, an index of dopamine storage capacity in brain, was reduced by 85% in putamen of patients with Parkinson's disease, and by 58% in the healthy elderly relative to the healthy young control subjects. Results of the present study support claims that storage capacity for dopamine in both caudate and putamen is more profoundly impaired in patients with Parkinson's disease than is the capacity for DOPA utilization, calculated by conventional FDOPA net influx plots. The present results furthermore constitute the first demonstration of an abnormality in the cerebral utilization of FDOPA in caudate and putamen as a function of normal aging, which we attribute to loss of vesicular storage capacity.

scholarly journals PARK Genes Link Mitochondrial Dysfunction and Alpha-Synuclein Pathology in Sporadic Parkinson’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Wen Li ◽  
YuHong Fu ◽  
Glenda M. Halliday ◽  
Carolyn M. Sue
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Lewy Pathology ◽  
Age Related ◽  
Promising Therapeutic Approach ◽  
Park Genes

Parkinson’s disease (PD) is an age-related neurodegenerative disorder affecting millions of people worldwide. The disease is characterized by the progressive loss of dopaminergic neurons and spread of Lewy pathology (α-synuclein aggregates) in the brain but the pathogenesis remains elusive. PD presents substantial clinical and genetic variability. Although its complex etiology and pathogenesis has hampered the breakthrough in targeting disease modification, recent genetic tools advanced our approaches. As such, mitochondrial dysfunction has been identified as a major pathogenic hub for both familial and sporadic PD. In this review, we summarize the effect of mutations in 11 PARK genes (SNCA, PRKN, PINK1, DJ-1, LRRK2, ATP13A2, PLA2G6, FBXO7, VPS35, CHCHD2, and VPS13C) on mitochondrial function as well as their relevance in the formation of Lewy pathology. Overall, these genes play key roles in mitochondrial homeostatic control (biogenesis and mitophagy) and functions (e.g., energy production and oxidative stress), which may crosstalk with the autophagy pathway, induce proinflammatory immune responses, and increase oxidative stress that facilitate the aggregation of α-synuclein. Thus, rectifying mitochondrial dysregulation represents a promising therapeutic approach for neuroprotection in PD.

scholarly journals Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

2012 ◽  
Vol 45 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Karine Rezende-Oliveira ◽  
Ronaldo Rodrigues Sarmento ◽  
Virmondes Rodrigues Junior
Keyword(s):  
Immune System ◽  
Trypanosoma Cruzi ◽  
Whole Blood ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Innate Immune ◽  
Peripheral Blood Mononuclear ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Whole Blood Cells

INTRODUCTION: The innate immune response is the first mechanism of protection against Trypanosoma cruzi, and the interaction of inflammatory cells with parasite molecules may activate this response and modulate the adaptive immune system. This study aimed to analyze the levels of cytokines and chemokines synthesized by the whole blood cells (WBC) and peripheral blood mononuclear cells (PBMC) of individuals seronegative for Chagas disease after interaction with live T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-α, TGF-β, CCL-5, CCL-2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC, even after incubation with live trypomastigotes. Production of TNF-α by both PBMC and WBC was significantly higher after stimulation with trypomastigotes. Only PBMC produced significantly higher levels of IL-12 after parasite stimulation. Stimulation of cultures with trypomastigotes induced an increase of CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T. cruzi may induce the production of cytokines and chemokines by cells of the innate immune system through the activation of specific receptors not evaluated in this experiment. The ability to induce IL-12 and TNF-α contributes to shift the adaptive response towards a Th1 profile.

Effect of polyherbal drug Majun falasfa on the transgenic Drosophila model of Parkinson’s Disease

2020 ◽  
Vol 07 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Mohammad Rashid
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Unani Medicine ◽  
Age Related ◽  
Drosophila Model ◽  
Climbing Ability ◽  
Transgenic Drosophila

Aim: The effect of Majun Falasfa (MF) was studied on the transgenic Drosophila expressing human alpha synuclein panneurally. Background: MF is a Unani medicine used for enhancing mental power and treating kidney, joint pains and urinary tract diseases. It is also use for phlegmatic diseases. It is also being used in age related dementia and to counter the effects of ageing. Methods: The equivalents of recommended dose for human were established for 20g of fly food i.e. 0.0014, 0.0028, 0.0042 and 0.0056g per 20g of diet. The PD flies were allowed to feed on it for 24 days before studying its effect on cognitive and oxidative stress parameters. Immunohistochemistry was also performed study the effect of MF on human alpha synuclein expression. Results: The exposure to MF increased the life span and improves the activity of PD flies. MF delayed the loss of climbing ability of PD flies. The exposure of PD flies to MF significantly reduced the oxidative stress and improves the antioxidant enzymes homeostasis compared to unexposed PD flies. The exposure to MF reduces the formation of Lewy bodies as is evident by immunohistochemistry. Conclusion: MF is potent in reducing the PD (Parkinson’s disease) symptoms being mimicked in the transgenic flies.

Mitochondria as an Easy Target to Oxidative Stress Events in Parkinson's Disease

2012 ◽  
Vol 11 (4) ◽  
pp. 430-438 ◽  
Author(s):  
Marcella Reale ◽  
Mirko Pesce ◽  
Medha Priyadarshini ◽  
Mohammad A Kamal ◽  
Antonia Patruno
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease
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