Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 213, P. 164 - 173

Published: Jan. 19, 2024

Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological animal model studies suggest an association with pesticides other environmental toxins. However, the cellular mechanisms underlying toxin induced P-ANS dysfunctions remain unclear. Here, we mapped global transcriptome changes in human pluripotent stem cell (iPSC) derived sympathetic neurons during inhibition mitochondrial respiratory chain by PD-related pesticide, rotenone. We revealed distinct profiles between acute chronic exposure to In stage, there was down regulation specific cation channel genes, known mediate electrophysiological activity, while exhibited dysregulation anti-apoptotic Golgi apparatus-related pathways. Moreover, sodium voltage-gated subunit SCN3A/Nav1.3 as potential biomarker associated PD. Our analysis rotenone-altered coding non-coding may thus provide insight into pathological signaling events progression.

Language: Английский

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The functional brain connectome in isolated rapid eye movement sleep behavior disorder and Parkinson’s disease

Sleep Medicine, Journal Year: 2024, Volume and Issue: 117, P. 184 - 191

Published: March 19, 2024

Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alpha-synucleinopathies such as Parkinson's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed PD. However, relatively little is known about whole-brain functional iRBD. Here, we characterize connectome compared with PD patients and healthy controls (HC) using resting-state MRI (rs-fMRI).

Language: Английский

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Investigation of nonmotor symptoms and their clinical correlates in patients with Parkinson’s disease

Neurodegenerative Disease Management, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: March 17, 2025

Background In this study, we aimed to investigate the clinical features of a large group patients with Parkinson's disease (PD), paying particular attention nonmotor symptom (NMS) load. Secondly, correlates NMSs using results various assessments.

Language: Английский

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Neuroimaging-based data-driven subtypes of spatiotemporal atrophy due to Parkinson’s disease

Brain Communications, Journal Year: 2025, Volume and Issue: 7(2)

Published: Jan. 1, 2025

Parkinson's disease is the second most common neurodegenerative disease. Despite this, there are no robust biomarkers to predict progression, and understanding of mechanisms limited. We used Subtype Stage Inference algorithm characterize heterogeneity in terms spatiotemporal subtypes macroscopic atrophy detectable on T1-weighted MRI-a successful approach other diseases. trained model covariate-adjusted cortical thicknesses subcortical volumes from largest known MRI dataset disease, Enhancing Neuroimaging through Meta-Analysis consortium Disease (n = 1100 cases). tested by analyzing clinical progression over up 9 years openly-available data people with Progression Markers Initiative 584 Under cross-validation, our analysis supported three subtypes, named for location earliest affected regions as: 'Subcortical' 359, 33%), 'Limbic' 237, 22%) 'Cortical' 187, 17%). A fourth subgroup having sub-threshold/no was 'Sub-threshold atrophy' 317, 29%). Statistical differences scores existed between no-atrophy but not among subtypes. This suggests that prime delineator severity, rather than location. Future work unravelling biological should leverage more sensitive neuroimaging modalities multimodal data.

Language: Английский

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Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson’s disease

Journal of Neurology, Journal Year: 2024, Volume and Issue: 271(4), P. 2019 - 2030

Published: Jan. 6, 2024

Language: Английский

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Clinical characteristics of patients with Parkinson's disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart

Journal of the Neurological Sciences, Journal Year: 2024, Volume and Issue: 458, P. 122932 - 122932

Published: Feb. 13, 2024

Language: Английский

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A Population‐Based Approach to the Argument on Brain‐First and Body‐First Pathogenesis of Lewy Body Disease

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(3), P. 551 - 559

Published: June 11, 2024

To explore the clinical progression of brain-/body-first categories within Lewy body disease (LBD): Parkinson's (PD), dementia with bodies (DLB), and PD dementia.

Language: Английский

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To the Gut Microbiome and Beyond: The Brain-First or Body-First Hypothesis in Parkinson’s Disease

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

There is continued debate regarding Parkinson’s disease etiology and whether it originates in the brain or begins gut. Recently, evidence has been provided for both, with onset presenting as either a “body-first” “brain-first” progression. Most research indicates those have an altered gut microbiome compared to controls. However, some studies do not report differences, potentially due body-first progression type. Based on of each proposed progression, individuals may exhibit microbiomes, i.e., where short-chain fatty acid producing bacteria are reduced, while brain-first not. Future should consider this hypothesis investigate differences exist between type This further elucidate impact show how be homogenous across disease.

Language: Английский

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Long Short-Term Memory-Based Deep Learning Models for Screening Parkinson’s Disease Using Sequential Diagnostic Codes

Journal of Clinical Neurology, Journal Year: 2023, Volume and Issue: 19(3), P. 270 - 270

Published: Jan. 1, 2023

It is challenging to detect Parkinson's disease (PD) in its early stages, which has prompted researchers develop techniques based on machine learning methods for detecting PD. However, previous studies did not fully incorporate the slow progression of PD over a long period time nor consider that symptoms occur time-sequential manner. Contributing literature PD, relied heavily cross-sectional data, this study aimed method can process time-series information using short-term memory (LSTM) algorithm.We sampled 926 patients with and 9,260 subjects without medical-claims data. The LSTM algorithm was tested diagnostic histories, contained codes their respective information. We compared prediction power 12-month under two different settings 4 years prior first diagnosis.The model trained most-recent had best performance, an accuracy 94.25%, sensitivity 82.91%, specificity 95.26%. other three models (12-month from 2, 3, prior) were found have comparable performances, accuracies 92.27%, 91.86%, 91.81%, respectively. areas curve our data ranged 0.839 0.923.We explored possibility specialists could benefit proposed as detection

Language: Английский

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REM sleep behavior disorder correlates with constipation in de novo Chinese Parkinson’s disease patients

Neurological Sciences, Journal Year: 2022, Volume and Issue: 44(1), P. 191 - 197

Published: Sept. 13, 2022

Language: Английский

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