ArticleChinese medical journal2017
Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease.
Article in Chinese medical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson's disease: a systematic review.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease.Neuroscience bulletin · 2026Article
- Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.Metabolic brain disease · 2026Review
- Dopaminergic Degeneration Differentially Modulates Primary Motor Cortex Activity and Motor Behavior in Hemiparkinsonian Rats.Brain sciences · 2025Article
- Review
- The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective.Aging and disease · 2024Review
- Targeting sleep and the circadian system as a novel treatment strategy for Parkinson's disease.Journal of neurology · 2024Article
- Review
- Chronobiology of Parkinson's disease: Past, present and future.The European journal of neuroscience · 2023Review
- Hypothalamic A11 Nuclei Regulate the Circadian Rhythm of Spinal Mechanonociception through Dopamine Receptors and Clock Gene Expression.Life (Basel, Switzerland) · 2022Article
- Review
- Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm.Frontiers in bioscience (Landmark edition) · 2021Review
- Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways.Biomolecules · 2021Review
- Recent Progress in Non-motor Features of Parkinson's Disease with a Focus on Circadian Rhythm Dysregulation.Neuroscience bulletin · 2021Review
- L-3,4-Dihydroxyphenylalanine Recovers Circadian Rhythm Disturbances in the Rat Models of Parkinson's Disease by Regulating the D1R-ERK1/2-mTOR Pathway.Frontiers in aging neuroscience · 2021Article
- Cognitive impairment with diabetes mellitus and metabolic disease: innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways.Expert review of clinical pharmacology · 2020Review
- Circadian Rhythm Abnormalities in Parkinson's Disease from Humans to Flies and Back.International journal of molecular sciences · 2018Review
- Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors.Current neurovascular research · 2018Review
- Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer.Current neurovascular research · 2017Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundParkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.
methodsThe rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days. Rotarod test, footprint test, and open-field test were carried out to evaluate the motor function. Striatum, suprachiasmatic nucleus (SCN), liver, and plasma were collected at 6:00, 12:00, 18:00, and 24:00. Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes. Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin. High-performance liquid chromatography was used to measure the neurotransmitters. Analysis of variance was used for data analysis.
resultsL-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test ( P < 0.01, P < 0.001, respectively). After L-DOPA treatment, Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 ( P < 0.01) and 24:00 ( P < 0.001). In the striatum, the expression of Bmal1, Rorα was lower than that in the 6-OHDA group at 18:00 (P < 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00. In liver, L-DOPA did not affect the rhythmicity and expression of these clock genes (P > 0.05). In addition, the cortisol secretion was increased (P > 0.05), but melatonin was further inhibited after L-DOPA treatment at 6:00 (P < 0.01).
conclusionsIn the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.
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