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RESEARCH PAPER ANALYSIS

Motoneuron Excitability in Parkinson's Disease: Effects of Dopaminergic Medication.

This human study found elevated motoneuron excitability and PIC-related amplification in people with Parkinson's disease compared with age-matched controls, and that dopaminergic medication did not fully normalize these measures.

PMID42003164
JournalJournal of neurophysiology
Publication Date2026-04-19
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

This human study found elevated motoneuron excitability and PIC-related amplification in people with Parkinson's disease compared with age-matched controls, and that dopaminergic medication did not fully normalize these measures.

WHY IT MATTERS

Research significance

By implicating persistent intrinsic motoneuron changes and PICs that are insensitive to dopamine replacement, the work points to non-dopaminergic targets (ion channels, alternate monoaminergic systems) and electrophysiologic biomarkers that could be exploited for therapeutic discovery.

ABSTRACT

Source abstract

Dopamine is a critical neuromodulator of motor function. In Parkinson's disease (PD), the degeneration of dopaminergic neurons not only disrupts motor function but may also alter motoneuron excitability, contributing to motor deficits. The aim of this study was to investigate motoneuron excitability in people with PD during ON and OFF medication states and to compare these responses with controls of similar age. Fourteen people with PD (4 females) were tested in two sessions (ON and OFF medication), and 13 controls (5 females) completed the same protocol in one session. Participants performed slow triangular elbow flexion isometric contractions to 30% of their maximum voluntary contraction (MVC). Motor unit discharge rates, recruitment threshold, discharge rate hysteresis (∆F), brace height, acceleration and attenuation slopes, ascending and descending rate modulations and self-sustained discharge duration were calculated. People with PD showed higher initial discharge rates (p < 0.05) and lower recruitment thresholds (p < 0.001) in both medication states compared to controls, with no significant differences between the OFF and ON conditions (p > 0.05). ΔF and acceleration slope were both elevated in the OFF state compared with controls (p = 0.04 and p = 0.05, respectively), with no significant medication effects on either measure (p > 0.05). Motoneuron excitability was higher in people with PD compared with controls and dopaminergic medication does not fully normalize motoneuron excitability or suppress PIC-related amplification. These finding raising the possibility that changes associated with long-term monoaminergic loss may not be fully restored by medication.

SUPPORTING PAPER SET

32 more papers to review

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Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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