Dabigatran Combined With Benztropine Ameliorates Cobalt Chloride-Induced Parkinsonism in Rats, Restores Protease-Activated Receptor 1 (PAR1), and Mitigates Oxidative Stress

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

The presumed implication of thromboembolic and oxidative stress pathways in parkinsonism guided the current research toward exploration anticoagulant dabigatran etexilate (DE) as a thrombin inhibitor cobalt chloride (CoCl2)-induced (CIP) model, model significance to industrial toxins-related health issues. Oral CoCl2 (12.5 mg/kg) was administered daily for 60 days, with introduction benztropine mesylate (BM) (10 and/or DE (3 on day 31. Rearing, postural instability, pasta handling were evaluated, followed by histopathologic examination substantia nigra (SN) striatum (STR). expressions brain dopamine receptor 2 (D2 ), adenosine 1 (A1) 2A (A2A), protease-activated (PAR1), well levels (DA), endothelin (ET1), malondialdehyde (MDA), glutathione (GSH), assessed. BM+DE restored number rears control level, compared being reduced CIP model. first, second, third, average displacement distances superior either BM or restoring time finish eating adjustments forepaws while after affected DA level D2 level. A1 A2A , increasing A1/A2A beyond PAR1 ET1 levels. MDA both GSH exhibited highest percentage preserved neurons SN, which negatively correlated MDA. offers therapeutic potential triggered chronic exposure CoCl2. thrombin-related factors modulation dopaminergic-adenosinergic crosstalk is plausible.

Language: Английский

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Eye Tracking in Parkinson’s Disease: A Review of Oculomotor Markers and Clinical Applications

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 362 - 362

Published: March 31, 2025

(1) Background. Eye movement abnormalities are increasingly recognized as early biomarkers of Parkinson's disease (PD), reflecting both motor and cognitive dysfunction. Advances in eye-tracking technology provide objective, quantifiable measures saccadic impairments, fixation instability, smooth pursuit deficits, pupillary changes. These advances offer new opportunities for diagnosis, monitoring, neurorehabilitation. (2) Objective. This narrative review explores the relationship between oculomotor dysfunction PD pathophysiology, highlighting potential applications eye tracking clinical research settings. (3) Methods. A comprehensive literature was conducted, focusing on peer-reviewed studies examining PD. Relevant publications were identified through PubMed, Scopus, Web Science, using key terms, such "eye movements disease", "saccadic control neurodegeneration", "fixation instability PD", "eye-tracking assessment". Studies integrating machine learning (ML) models VR-based interventions also included. (4) Results. Patients with exhibit distinct abnormalities, including hypometric saccades, prolonged latency, increased anti-saccade errors. impairments correlate executive progression. Fixation altered responses further support role metrics non-invasive biomarkers. Emerging AI-driven show promise automated diagnosis progression tracking. (5) Conclusions. provides a reliable, cost-effective tool detection, assessment, rehabilitation. Future should focus standardizing protocols, validating predictive AI models, into multimodal treatment strategies.

Language: Английский

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Bimanual coordination and neuromuscular synchronization in Parkinson’s disease and healthy adults

Experimental Brain Research, Journal Year: 2025, Volume and Issue: 243(4)

Published: April 1, 2025

Language: Английский

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Anticipatory reaching motor behavior characterizes patients within the Alzheimer’s disease continuum in a virtual reality environment

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 9, 2025

Alzheimer's Disease (AD) is characterized by progressive declines in cognitive and motor functions, impairing daily activities. Traditionally, AD diagnosis relies on assessments, but emerging evidence highlights function deficits as early indicators of Mild Cognitive Impairment (MCI). These declines, which often precede symptoms, include slower less accurate reaching movements. This study explored actions a Virtual Reality (VR) environment MCI patients to identify their link decline. The involved 61 right-handed participants (19 AD, 21 MCI, healthy age-matched controls), screened for health using Mini-Mental State Examination (MMSE). Participants performed upper-limb tasks (sequentially targets) (VR). Kinematic data was recorded analyzed focusing task success rate, frequency anticipatory responses, direction responses. Statistical analysis Generalized Linear Mixed Models differentiate the three groups based performance metrics, anticipation behavior, correlation between rate MMSE score. Both showed more responses than controls (HC), inversely related rates function. exhibited lower higher biased toward previous trial targets, suggesting impaired planning or difficulty adapting new cues. an intermediate pattern, with HC comparable rates. results highlight crucial role behavior performance, displaying most pronounced deficits. significant impairments movements patients, particularly terms observed suggest that kinematic metrics could serve biomarkers intervention. findings emphasize importance combining sensorimotor assessments detection AD-related dysfunctions. Additionally, they potential VR-based rehabilitation promising approach address continuum, improving both outcomes.

Language: Английский

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A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure

BMC Neurology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 23, 2024

Abstract Background Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss vestibular function. Real-world tests require complex setups. In contrast, simple pointing at targets a three-dimensional environment is basic sensorimotor ability which provides an alternative measure orientation memory bedside. The aim this study was to test the reliability previously established 3D-Real-World Pointing Test (3D-RWPT) patients with due different neurodegenerative disorders, bilateral vestibulopathy, combination both compared healthy participants. Methods 3D-RWPT performed using static array front seated participant before and, as transformation task, after 90-degree body rotation around yaw-axis. Three groups were enrolled: (1) chronic vestibulopathy (BVP) normal cognition ( n = 32), (2) function 28), (3) combined BVP 9). control group consisted age-matched participants (HP) without deficits 67). Analyses focused on paradigm-specific mean angular deviation azimuth (horizontal) polar (vertical) planes, preferred strategy (egocentric allocentric), resulting shape configuration relative stimulus array. Statistical analysis age-corrected ANCOVA-testing Bonferroni correction correlation Spearman’s rho. Results Patients employed more egocentric strategies while but HP used world-based solutions (pBonf 5.78 × 10-3**). Differences accuracy only found plane, unveiling unique patterns where showed decreased tasks < 0.001***) struggled post-rotation 0.001***). Overall performance still adequate some significantly when deficit. Conclusion fast memory. Cognitive led shift from allocentric less controls. This supports view that hinder mental buildup pattern represented geometrical form. Vestibular hypofunction negatively affected plane. most severe impairments (angular deviation, figure frame configuration) deficits.

Language: Английский

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Perspective on investigation of neurodegenerative diseases with neurorobotics approaches

Neuromorphic Computing and Engineering, Journal Year: 2023, Volume and Issue: 3(1), P. 013001 - 013001

Published: March 1, 2023

Abstract Neurorobotics has emerged from the alliance between neuroscience and robotics. It pursues investigation of reproducing living organism-like behaviors in robots by means embodiment computational models central nervous system. This perspective article discusses current trend implementing tools for pressing challenge early-diagnosis neurodegenerative diseases how neurorobotics approaches can help. Recently, advances this field have allowed testing some neuroscientific hypotheses related to brain diseases, but lack biological plausibility developed musculoskeletal systems limited understanding underlying mechanisms that lead deficits motor cognitive tasks. Key aspects methods enhance reproducibility natural observed healthy impaired brains are proposed perspective. In long term, goal is move beyond finding therapies look into researchers use reduce on humans as well find root causes disease.

Language: Английский

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Assessing traffic-related air pollution-induced fiber-specific white matter degradation associated with motor performance declines in aged rats

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 263, P. 115373 - 115373

Published: Aug. 22, 2023

Fine particulate matter (PM2.5) is thought to exacerbate Parkinson's disease (PD) in the elderly, and early detection of PD progression may prevent further irreversible damage. Therefore, we used diffusion tensor imaging (DTI) for probing microstructural changes after late-life chronic traffic-related PM2.5 exposure. Herein, 1.5-year-old Fischer 344 rats were exposed clean air (control), high-efficiency (HEPA)-filtered ambient (HEPA group), (PM2.5 group, 9.933 ± 1.021 µg/m3) 3 months. Rotarod test, DTI tractographic analysis, immunohistochemistry performed end study period. Aged exhibited motor impairment with decreased fractional anisotropy tyrosine hydroxylase expression olfactory nigrostriatal circuits, indicating disrupted white integrity dopaminergic (DA) neuronal loss. Additionally, increased radial diffusivity lower myelin basic protein group suggested ageing demyelination exacerbated by Significant production tumor necrosis factor-α was also observed exposure, revealing potential inflammation injury multiple fiber tracts DA pathways. Microstructural demonstrated links between PM2.5-induced inflammatory behavioral performance, indication pre-manifestation DTI-based biomarkers elderly.

Language: Английский

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Striatal Dopamine Contributions to Skilled Motor Learning

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(26), P. e0240242024 - e0240242024

Published: May 28, 2024

Coordinated multijoint limb and digit movements-"manual dexterity"-underlie both specialized skills (e.g., playing the piano) more mundane tasks tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson's disease, a range of other pathologies. Clinical observations, well basic investigations, suggest that corticostriatal circuits play critical role learning performing skills. Furthermore, dopaminergic signaling these regions is implicated synaptic plasticity learning. Nonetheless, striatal dopamine skilled remains poorly understood. Here, we use fiber photometry paired genetically encoded sensor to investigate release male female mice they learn perform reaching task. Dopamine rapidly increases during reach peaks near pellet consumption. In dorsolateral striatum, dynamics are faster than dorsomedial ventral striatum. Across training, performance improves, shifts from consumption cues predict availability, particularly medial areas prediction errors present across reduced after an unsuccessful reach. These findings show behaviors change differentially regulated subregions.

Language: Английский

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Sensory context of initiation-cue modulates action goal-relevant neural representations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Abstract The ability to produce goal-directed movement relies on the integration of diverse sources sensory information specific task goal. Neural representations goal-relevant features, such as target location and gaze direction, have been well studied in sensorimotor areas. It remains less clear whether motor are influenced by changes initiation-relevant information, a go-cue that provides no about location. We used Bayesian pattern component modelling fMRI data during delayed reach with either visual or audiovisual go-cues explore neural goal-related features areas modulated information. found direction primary areas, posterior parietal cortex, were sensitive was cued go-cue. These findings indicate central nervous system flexibly delegates tasks ‘where’ move ‘when’ based available context, even if stimuli provide additional

Language: Английский

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Parkinson’s Disease affects the contextual control, but not the expression, of a rapid visuomotor response that initiates visually-guided reaching: Evidence for multiple, interacting motor pathways and implications for motor symptoms in Parkinson’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Abstract Despite significant deficits in voluntary motor control, patients with Parkinson’s disease (PD) can generate reflexive or stimulus-driven movements. How are such spared capabilities realized? Here, we recorded upper limb muscle activity PD and age-matched healthy controls (HCs) as they reached either toward away from a visual stimulus. The task promoted express visuomotor responses (EVRs), which brief bursts of recruitment time-locked (<100 ms) to stimulus presentation that thought originate the midbrain superior colliculus. Across two experiments, observed remarkable sparing latency magnitude EVRs PD, but decreased ability for contextually modulate EVR depending on trial instruction. Magnitudes were strikingly strongly correlated Reaction times Error rates, despite compromised levels electromyographic (EMG) subsequent phases activity, predicted lower Peak velocities. Our results consistent differential influence parallel-but-interacting subcortical cortical pathways converge onto brainstem spinal circuits during reaching. This is discriminable even within single selective stimulus-aligned not movement-aligned recruitment, has implications our understanding cognitive seen PD.

Language: Английский

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