Acute Levodopa Dosing Around-the-clock Ameliorates REM Sleep Without Atonia in Hemiparkinsonian rats
Document Type
Article
Publication Date
2019
College/Unit
School of Medicine
Department/Program/Center
Neurology
Abstract
- Article
- Open Access
- Published: 29 November 2019
Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats
- Vishakh Iyer,
- Quynh Vo,
- Anthony Mell,
- Siven Chinniah,
- Ashley Zenerovitz,
- Kala Venkiteswaran,
- Allen R. Kunselman,
- Jidong Fang &
- Thyagarajan Subramanian
npj Parkinson's Disease volume 5, Article number: 27 (2019) Cite this article
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Abstract
Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.
Digital Commons Citation
Iyer, Vishakh; Vo, Quynh; Mell, Anthony; Chinniah, Siven; Zenerovitz, Ashley; Venkiteswaran, Kala; Kunselman, Allen R.; Fang, Jidong; and Subramanian, Thyagarajan, "Acute Levodopa Dosing Around-the-clock Ameliorates REM Sleep Without Atonia in Hemiparkinsonian rats" (2019). Faculty & Staff Scholarship. 1386.
https://researchrepository.wvu.edu/faculty_publications/1386
Source Citation
Iyer, V., Vo, Q., Mell, A., Chinniah, S., Zenerovitz, A., Venkiteswaran, K., Kunselman, A. R., Fang, J., & Subramanian, T. (2019). Acute levodopa dosing around-the-clock ameliorates REM sleep without atonia in hemiparkinsonian rats. Npj Parkinson’s Disease, 5(1). https://doi.org/10.1038/s41531-019-0096-2
Comments
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