Coherent Changes in Neural Motor Network Activity during Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease DOI Creative Commons

E. S. Brazhnik,

Ivan Mysin, Lyudmila B. Popova

et al.

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(12)

Published: Dec. 24, 2024

Background: Long-term use of levodopa, a metabolic precursor dopamine (DA) for alleviation motor symptoms in Parkinson’s disease (PD), can cause serious side effect known as levodopa-induced dyskinesia (LID). With the development LID, high-frequency gamma oscillations (~100 Hz) are registered cortex (MCx) patients with PD and rats experimental PD. Studying alterations activity within major components networks during transition from levodopa-off state to provide useful information about their contribution abnormal LID. Methods: Freely moving unilateral 6-hydroxydopamine hydrobromide (6-OHDA)-induced nigral DA cell lesions were administered high dose levodopa 7 days. Local field potentials (LFPs) neuronal recorded electrodes implanted (MCx), ventromedial nucleus thalamus (VM), substantia nigra pars reticulata (SNpr). Results: Levodopa reduced power beta (30–36 associated bradykinesia three divisions neural network (MCx, VM, SNpr) prompted subsequent emergence robust (80–120 VM MCx, but not SNpr, LFPs. Gamma strongly occurrence involuntary movements (AIMs) accompanied by an increase spiking rates MCx enlarged spike-LFP synchronization cortical (68% 34% MCx). In contrast, SNpr LFPs did exhibit most recordings (87%) was largely decreased synchronized or Administration antidyskinetic drug 8-hydroxy-2-(dipropylamino)-tetraline (8-OH-DPAT) restored initial characteristics Hz oscillations), activity, bradykinesia. Inhibition neurons gamma-aminobutyric acid (GABA-A)-agonist muscimol LID eliminated dyskinesia, suggesting that critical expression AIMs. chemogenetic activation both dyskinesia. Conclusions: These findings suggest treatment leads crucial reduction inhibitory control over due large decline GABAergic projecting neurons, which causes persistent hyperactivity circuits, leading appearance thalamocortical

Language: Английский

Electrophysiological Alterations in the Progression of Parkinson's Disease and the Therapeutic Effect of Tetrabenazine on Rats With Levodopa‐Induced Dyskinesia DOI Creative Commons
Yue-Wei Bi, Pengfei Wang, Min Li

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Aims Dopamine replacement therapy is the backbone of Parkinson's disease (PD) treatment. However, long‐term levodopa ( L ‐DOPA) administration can lead to severely disabling motor complication L‐DOPA‐induced dyskinesia (LID), for which standard, effective currently lacking. This study was conducted characterize distinct neural electrophysiological patterns involved in progression PD and examine efficacy tetrabenazine, a vesicular monoamine transporter‐2 inhibitor, alleviating its underlying mechanism. Methods Electrophysiological analysis performed obtain power spectrum density functional connectivity information from local field potential (LFP) data recorded primary cortex (M1) dorsolateral striatum (DLS) during different pathological states model rats. Behavioral tests abnormal involuntary movements (AIMs) scoring were confirm establishment assess LID severity. Results Increased beta oscillations abnormally strengthened causality M1 → DLS direction exaggerated beta‐band M1–DLS observed state. ‐DOPA suppressed activity augmented gamma DLS, with increased direction, as well elevated gamma‐band connectivity. Tetrabenazine strongly ameliorated dyskinetic manifestations. It reduced Conclusion abrogated aberrant improve symptoms, provides compelling evidence future clinical application therapy.

Language: Английский

Citations

0
Local Field Potentials and Neuron Activity in Motor Networks in Levodopa-Induced Dyskinesia in a Model of Parkinson’s Disease DOI

E. S. Brazhnik,

Ivan Mysin,

Н Ю Новиков

et al.

Neuroscience and Behavioral Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0
Boosting endogenous dopamine production: a novel therapeutic approach for Parkinson’s disease DOI
Erik H. Douma, Marten P. Smidt, Lars P. van der Heide

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(9), P. 800 - 803

Published: June 25, 2024

Language: Английский

Citations

2
Cell- and state-specific plasticity of striatal glutamatergic synapses is critical to the expression of levodopa-induced dyskinesia DOI Open Access

Weixing Shen,

Shenyu Zhai, Veronica Francardo

et al.

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

Published: June 14, 2024

Abstract Levodopa-induced dyskinesia (LID) is a debilitating complication of symptomatic therapy in Parkinson’s disease (PD). Although there compelling evidence that striatal pathophysiology major driver LID, the circuit-specific mechanisms contributing to dysfunction remain obscure. This lack clarity reflected limited options for diminishing established LID. To address this gap, molecular, cellular, and behavioral strategies were used interrogate indirect pathway spiny projection neurons (iSPNs) mouse model These studies revealed LID induction led an up-regulation GluN2B-containing N-methyl-d-aspartate receptors (NMDARs) specifically at iSPN glutamatergic synapses. was correlated with increased numbers ‘silent’ synapses hours after levodopa treatment. In ‘off-state’, long-term potentiation (LTP) readily induced blocked by antagonists adenosine type 2 (A2aRs) or NMDARs. Systemic administration A2aR antagonist tozedenant beginning off-state significantly reduced development More importantly, knocking down expression GRIN2B mRNA iSPNs dramatically attenuated both without compromising beneficial effects on movement. Taken together, these demonstrate dyskinesiogenic doses trigger cell-specific synaptic adaptations during make important contribution network underlying suggest targeting NMDARs could be therapeutically useful.

Language: Английский

Citations

1
Functional motor network abnormalities associated with levodopa-induced dyskinesia in Parkinson’s disease: A systematic review DOI Creative Commons
Birgitte Liang Chen Thomsen, Mikkel C. Vinding, David Meder

et al.

NeuroImage Clinical, Journal Year: 2024, Volume and Issue: 44, P. 103705 - 103705

Published: Jan. 1, 2024

Parkinson's disease (PD) can be effectively treated with levodopa and dopamine agonists but leads to levodopa-induced dyskinesia (LID) in most patients the long run. Various functional brain mapping techniques are used explore alterations motor networks associated LID. This pre-registered review (PROSPERO: CRD42022320830) summarizes network abnormalities reported studies of We included using MRI, EEG, PET, SPECT, or TMS at least 10 LID patients. For completeness, we 5-9 a table. Some these were also incorporated into if other same method. Thirty met our pre-defined criteria. Patients showed stronger motor-related activation connectivity premotor cortical areas putamen after intake relative PD without Decreased was found right inferior frontal cortex. increased excitability blunted plasticity LID, while "inhibitory" repetitive prefrontal control cerebellum produced transient anti-dyskinetic effects. Overall, sample sizes small, number per modality limited, lacked independent replication. The encompass changes activity, connectivity, excitability, execution networks. A comprehensive understanding how manifests level will guide future development stimulation-based therapies for

Language: Английский

Citations

1
Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering DOI Creative Commons
Cristina Alcacer, Andreas Klaus, Marcelo Mendonça

et al.

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

Published: Sept. 8, 2024

L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinsońs disease and the most common hyperkinetic disorder basal ganglia origin. Abnormal activity striatal D1 D2 spiny projection neurons (SPNs) critical for LID, yet link between SPN patterns specific dyskinetic movements remains unknown. To explore this, we developed novel method clustering based on high-resolution motion sensors video recordings. In mouse model this identified two main types pathological rotations, all absent during normal behavior. Using single-cell resolution imaging, found that sets both D2-SPNs were abnormally active these movements. Under baseline conditions, same behaviors sharing physical features with LID These findings indicate ensembles behavior-encoding D1- form new combinations hyperactive mediating

Language: Английский

Citations

0
Abnormal Hyperactivity of Specific Striatal Ensembles Encodes Distinct Dyskinetic Behaviors Revealed by High-Resolution Clustering DOI
Cristina Alcacer, Andreas Klaus, Marcelo Mendonça

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
Local field potentials and neural activity in motor networks in levodopa-induced dykinesia in a model of Parkinson’s disease DOI

E. S. Brazhnik,

Ivan Mysin,

Н Ю Новиков

et al.

Журнал высшей нервной деятельности им И П Павлова, Journal Year: 2024, Volume and Issue: 74(5), P. 606 - 620

Published: Nov. 27, 2024

Language: Английский

Citations

0
Coherent Changes in Neural Motor Network Activity during Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease DOI Creative Commons

E. S. Brazhnik,

Ivan Mysin, Lyudmila B. Popova

et al.

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(12)

Published: Dec. 24, 2024

Background: Long-term use of levodopa, a metabolic precursor dopamine (DA) for alleviation motor symptoms in Parkinson’s disease (PD), can cause serious side effect known as levodopa-induced dyskinesia (LID). With the development LID, high-frequency gamma oscillations (~100 Hz) are registered cortex (MCx) patients with PD and rats experimental PD. Studying alterations activity within major components networks during transition from levodopa-off state to provide useful information about their contribution abnormal LID. Methods: Freely moving unilateral 6-hydroxydopamine hydrobromide (6-OHDA)-induced nigral DA cell lesions were administered high dose levodopa 7 days. Local field potentials (LFPs) neuronal recorded electrodes implanted (MCx), ventromedial nucleus thalamus (VM), substantia nigra pars reticulata (SNpr). Results: Levodopa reduced power beta (30–36 associated bradykinesia three divisions neural network (MCx, VM, SNpr) prompted subsequent emergence robust (80–120 VM MCx, but not SNpr, LFPs. Gamma strongly occurrence involuntary movements (AIMs) accompanied by an increase spiking rates MCx enlarged spike-LFP synchronization cortical (68% 34% MCx). In contrast, SNpr LFPs did exhibit most recordings (87%) was largely decreased synchronized or Administration antidyskinetic drug 8-hydroxy-2-(dipropylamino)-tetraline (8-OH-DPAT) restored initial characteristics Hz oscillations), activity, bradykinesia. Inhibition neurons gamma-aminobutyric acid (GABA-A)-agonist muscimol LID eliminated dyskinesia, suggesting that critical expression AIMs. chemogenetic activation both dyskinesia. Conclusions: These findings suggest treatment leads crucial reduction inhibitory control over due large decline GABAergic projecting neurons, which causes persistent hyperactivity circuits, leading appearance thalamocortical

Language: Английский

Citations

0