Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.

Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

REM sleep without atonia and vestibular-evoked myogenic potentials: clinical brainstem dysfunction in early-stage Parkinson's disease and isolated REM sleep behavior disorder.

OBJECTIVE: To determine whether the onset of rapid eye movement (REM) sleep behavior disorder (RBD) is associated with changes in brainstem neuronal pathway dysfunction as reflected by vestibular-evoked myogenic potentials (VEMPs) and to evaluate associations between VEMPs and REM sleep without atonia (RSWA) in patients with early-stage Parkinson's disease (PD) and isolated RBD (iRBD). METHODS: Eighty-two early-stage PD patients, 40 iRBD patients, and 41 healthy control individuals underwent one-night video-polysomnography (vPSG) and VEMPs examination. We compared cervical (cVEMP), ocular (oVEMP), and masseter (mVEMP) VEMP parameters among PD with RBD (PD + RBD), PD without RBD (PD-RBD), iRBD, and control groups and analyzed correlations between VEMPs and RSWA in PD and iRBD groups. RESULTS: The PD + RBD group showed delays in bilateral cVEMP (Lp13, Ln23, Rn23: all p < 0.05) and oVEMP (Ln10, Rn10, Rp15: all p < 0.05) peak latencies compared with the PD-RBD group. Total cVEMP scores were higher in the PD + RBD group than in the iRBD group (p = 0.033). In PD patients, phasic RSWA was correlated with total cVEMP scores (p = 0.003), and tonic RSWA was correlated with left oVEMP scores (p = 0.013). CONCLUSIONS: Brainstem neurophysiology as evidenced by altered VEMPs in patients with PD and iRBD could reflect disease evolvement. Moreover, VEMPs alterations may vary depending on the presence of RBD in PD patients. The associations between altered RSWA and VEMP parameters highlight the meaningfulness of detecting brainstem dysfunction in early-stage PD.