scholarly journals An Environmental Contributor to Parkinson’s Disease Causes a Hormetic Lifespan Effect in C. elegans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 935-935
Author(s):  
Jennifer Thies ◽  
Guy A Caldwell ◽  
Kim A Caldwell ◽  
Hanna Kim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ampk Signaling ◽  
C Elegans ◽  
Hormetic Effect ◽  
Low Concentrations ◽  
Significant Difference ◽  
Potential Risk Factors ◽  
Solvent Control ◽  
Hormetic Response

Abstract Only 5-10% of Parkinson’s Disease (PD) cases have a direct genetic origin; however, exposure to herbicides, pesticides, and interactions with soil are potential risk factors. PD is characterized by the loss of dopaminergic (DA) neurons and the formation of protein inclusions that contain α-synuclein (α-syn). Conversely, a soil bacterium, Streptomyces venezuelae (S. ven), produces a secondary metabolite that causes age- and dose- dependent DA neurodegeneration in C. elegans; it also exacerbates α-syn-induced DA neurodegeneration. Previous studies from our lab determined that exposure to the S. ven metabolite caused oxidative stress, mitochondrial fragmentation and enhanced reactive oxygen species (ROS). Here we report that exposure to S. ven metabolite causes a hormetic effect on C. elegans lifespan, where low concentrations (5X) extend lifespan in N2 animals, but at higher concentrations (20X) lifespan is decreased. To further examine this hormetic response, we examined daf-16 mutants in this assay. daf-16 mutants displayed no significant differences between solvent and metabolite at both high and low concentrations, suggesting the hormetic response is daf-16 dependent. We also studied S. ven metabolite on C. elegans aging mutants. We investigated mutants in the AMPK signaling pathway and found when exposed to the 20X concentration of S. ven metabolite, aak-2 mutants displayed no significant difference between solvent and metabolite over lifespan. However, when aak-2 mutants were exposed to solvent control and the 5X concentration, mutants displayed a decreased lifespan. This suggests that functional aak-2 might be important for increased lifespan when combating toxicants following chronic exposure.

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.

scholarly journals Assessment of the Telomere Length and Its Effect on the Symptomatology of Parkinson’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 137
Author(s):  
Tina Levstek ◽  
Sara Redenšek ◽  
Maja Trošt ◽  
Vita Dolžan ◽  
Katarina Trebušak Podkrajšek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Telomere Length ◽  
Repetitive Sequences ◽  
Housekeeping Gene ◽  
Cellular Aging ◽  
Brain Diseases ◽  
Motor Complications ◽  
Telomere Attrition ◽  
Significant Difference

Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease.

scholarly journals Physiotherapy versus Consecutive Physiotherapy and Cognitive Treatment in People with Parkinson’s Disease: A Pilot Randomized Cross-Over Study

2021 ◽  
Vol 11 (8) ◽  
pp. 687
Author(s):  
Valentina Varalta ◽  
Paola Poiese ◽  
Serena Recchia ◽  
Barbara Montagnana ◽  
Cristina Fonte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Group ◽  
Cognitive Rehabilitation ◽  
Rating Scale ◽  
Verbal Learning ◽  
Functional Mobility ◽  
Cognitive Treatment ◽  
Rehabilitation Programs ◽  
Significant Difference

Background: Parkinson’s disease (PD) is characterized by motor and cognitive dysfunctions that can usually be treated by physiotherapy or cognitive training, respectively. The effects of consecutive physiotherapy and cognitive rehabilitation programs on PD deficits are less investigated. Objective: We investigated the effects of 3 months of physiotherapy (physiotherapy treatment group) or consecutive physiotherapy and cognitive (physiotherapy and cognitive treatment group) rehabilitation programs on cognitive, motor, and psychological aspects in 20 PD patients. Methods: The two groups switched programs and continued rehabilitation for another 3 months. The outcomes were score improvement on cognitive (Montreal Cognitive Assessment, Frontal Assessment Battery, Trail Making Test, Verbal Phonemic Fluency, Digit Span, and Rey Auditory Verbal Learning), motor (Unified Parkinson’s Disease Rating Scale-III, Berg Balance Scale, Two-Minute Walking Test, and Time Up and Go), and psychological (Beck Depression Inventory and State-Trait Anxiety Inventory) scales. Results: Between-group comparison revealed a significant difference in functional mobility between the two rehabilitation programs. Improvements in walking abilities were noted after both interventions, but only the patients treated with consecutive training showed better performance on functional mobility and memory tasks. Conclusion: Our findings support the hypothesis that consecutive physiotherapy plus cognitive rehabilitation may have a greater benefit than physiotherapy alone in patients with PD.

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 High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Salman Sohrabi ◽  
Danielle E. Mor ◽  
Rachel Kaletsky ◽  
William Keyes ◽  
Coleen T. Murphy
Keyword(s):  
Neural Network ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Throughput ◽  
Potential Candidate ◽  
Automated Scoring ◽  
C Elegans ◽  
Drug Candidates ◽  
Branched Chain ◽  
Approved Drugs

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

Lower vascular tone and larger plasma volume in Parkinson's disease with orthostatic hypotension

2011 ◽  
Vol 111 (2) ◽  
pp. 443-448 ◽  
Author(s):  
J. T. Groothuis ◽  
R. A. J. Esselink ◽  
J. P. H. Seeger ◽  
M. J. H. van Aalst ◽  
M. T. E. Hopman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Blood Flow ◽  
Orthostatic Hypotension ◽  
Vascular Resistance ◽  
Plasma Volume ◽  
Venous Pressure ◽  
Dilution Method ◽  
Significant Difference ◽  
Head Up Tilt

The pathophysiology of orthostatic hypotension in Parkinson's disease (PD) is incompletely understood. The primary focus has thus far been on failure of the baroreflex, a central mediated vasoconstrictor mechanism. Here, we test the role of two other possible factors: 1) a reduced peripheral vasoconstriction (which may contribute because PD includes a generalized sympathetic denervation); and 2) an inadequate plasma volume (which may explain why plasma volume expansion can manage orthostatic hypotension in PD). We included 11 PD patients with orthostatic hypotension (PD + OH), 14 PD patients without orthostatic hypotension (PD − OH), and 15 age-matched healthy controls. Leg blood flow was examined using duplex ultrasound during 60° head-up tilt. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. In a subset of 9 PD + OH, 9 PD − OH, and 8 controls, plasma volume was determined by indicator dilution method with radiolabeled albumin (125I-HSA). The basal leg vascular resistance was significantly lower in PD + OH (0.7 ± 0.3 mmHg·ml−1·min) compared with PD − OH (1.3 ± 0.6 mmHg·ml−1·min, P < 0.01) and controls (1.3 ± 0.5 mmHg·ml−1·min, P < 0.01). Leg vascular resistance increased significantly during 60° head-up tilt with no significant difference between the groups. Plasma volume was significantly larger in PD + OH (3,869 ± 265 ml) compared with PD − OH (3,123 ± 377 ml, P < 0.01) and controls (3,204 ± 537 ml, P < 0.01). These results indicate that PD + OH have a lower basal leg vascular resistance in combination with a larger plasma volume compared with PD − OH and controls. Despite the increase in leg vascular resistance during 60° head-up tilt, PD + OH are unable to maintain their blood pressure.

The Incidence of Parkinson's Disease: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 46 (4) ◽  
pp. 292-300 ◽  
Author(s):  
Lauren Hirsch ◽  
Nathalie Jette ◽  
Alexandra Frolkis ◽  
Thomas Steeves ◽  
Tamara Pringsheim
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Meta Analysis ◽  
Age Groups ◽  
Significant Heterogeneity ◽  
International Studies ◽  
Significant Difference ◽  
And Gender

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. Objective: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. Methods: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. Results: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). Conclusion: PD incidence generally increases with age, although it may stabilize in those who are 80+.

Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Potential Role ◽  
Alpha Synuclein ◽  
C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

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