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Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson's disease with the progression of disease and chronic treatment of levodopa. However, the specific cell assemblies mediating dyskinesia have not been fully elucidated. Here, we utilize the activity-dependent tool to identify three brain regions (globus pallidus external segment [GPe], parafascicular thalamic nucleus, and subthalamic nucleus) that specifically contain dyskinesia-activated ensembles. An intensity-dependent hyperactivity in the dyskinesia-activated subpopulation in GPe (GPe) is observed during dyskinesia. Optogenetic inhibition of GPe significantly ameliorates LID, whereas reactivation of GPe evokes dyskinetic behavior in the levodopa-off state. Simultaneous chemogenetic reactivation of GPe and another previously reported ensemble in striatum fully reproduces the dyskinesia induced by high-dose levodopa. Finally, we characterize GPe as a subset of prototypic neurons in GPe. These findings provide theoretical foundations for precision medication and modulation of LID in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228392 | PMC |
http://dx.doi.org/10.1016/j.xcrm.2024.101566 | DOI Listing |
Background: Although levodopa remains the gold standard treatment for Parkinson's disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations.
Objectives: To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population.
Neurol Ther
September 2025
Department of Neurology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Introduction: The pathogenesis of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) remains uncertain. Our work sought to examine the cortical gyrification pattern and its corresponding functional connectivity alterations, along with the underlying neurotransmitter information, in LID of PD.
Methods: We included 30 PD patients with LID (PD-LID group), 30 without LID (PD-NLID group), and 30 age- and gender-matched healthy controls (HC group).
Neurosci Res
August 2025
Department of Neurology, Hirosaki University Graduate School of Medicine, Japan.
We aimed to elucidate morphological changes in striatonigral projection neurons in a rat model of levodopa-induced dyskinesia (LID). Male Wistar rats underwent unilateral 6-hydroxydopamine lesioning to establish a hemiparkinsonian model. At 8 weeks postoperatively, the rats were allocated to either the levodopa-treated group or the saline-treated control group.
View Article and Find Full Text PDFNeuroscience
August 2025
Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address:
Levodopa-induced dyskinesia (LID) is a complication that occurs in many patients with Parkinson's disease. (-)-OSU6162 is a clinically tolerable dopamine stabilizer with affinity for both dopaminergic D receptors and serotonergic 5-HT receptors which has been shown to counteract LID in non-human primates. To investigate whether (-)-OSU6162 can dampen levodopa-induced abnormal involuntary movements in the unilateral 6-OHDA rat model of Parkinson's disease without impairing levodopa-induced improvement in motor functioning, female Sprague Dawley rats received complete unilateral lesioning of the medial forebrain bundle and were treated daily with levodopa/benserazide.
View Article and Find Full Text PDFNeurosci Bull
August 2025
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450015, China.
Cortico-thalamic projections (the hyper-direct pathway) are implicated in levodopa-induced dyskinesia (LID), a challenging complication in the advanced stages of Parkinson's disease (PD). Excessive beta and gamma activity in PD and LID has frequently been reported in recent cross-sectional studies. We aimed to investigate the temporal features of beta and gamma activity in the hyper-direct pathway during the development of PD and LID in rats, as well as the regulatory role of the dopamine receptors DI (D1Rs) and DIII (D3Rs) in these disorders.
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