Electrophysiological Alterations in the Progression of Parkinson's Disease and the Therapeutic Effect of Tetrabenazine on Rats With Levodopa-Induced Dyskinesia
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引用次数: 0
Abstract
Aims
Dopamine replacement therapy is the backbone of Parkinson's disease (PD) treatment. However, long-term levodopa (L-DOPA) administration can lead to the severely disabling motor complication L-DOPA-induced dyskinesia (LID), for which standard, effective therapy is currently lacking. This study was conducted to characterize the distinct neural electrophysiological patterns involved in the progression of PD and to examine the efficacy of tetrabenazine, a vesicular monoamine transporter-2 inhibitor, in alleviating dyskinesia and its underlying electrophysiological mechanism.
Methods
Electrophysiological analysis was performed to obtain power spectrum density and functional connectivity information from local field potential (LFP) data recorded from the primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states in PD model rats. Behavioral tests and abnormal involuntary movements (AIMs) scoring were conducted to confirm PD model establishment and assess LID severity.
Results
Increased beta oscillations and abnormally strengthened beta causality in the M1 → DLS direction and exaggerated beta-band M1–DLS functional connectivity were observed in the PD state. L-DOPA administration suppressed beta activity and augmented gamma power in the M1 and DLS, with increased gamma causality in the M1 → DLS direction and beta causality in the DLS → M1 direction, as well as elevated gamma-band M1–DLS functional connectivity. Tetrabenazine strongly ameliorated dyskinetic manifestations. It suppressed gamma power in the M1 and DLS, reduced gamma causality and increased beta causality in the M1 → DLS direction, reduced beta causality in the DLS → M1 direction, and reduced gamma-band M1–DLS functional connectivity.
Conclusion
Tetrabenazine abrogated aberrant gamma activity to improve LID symptoms, which provides compelling evidence for its future clinical application in LID therapy.
期刊介绍:
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.