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.

SIRT2 Is Critical for Sheep Oocyte Maturation through Regulating Function of Surrounding Granulosa Cells.

Oocyte in vitro maturation is crucial for in vitro embryo production technology, which provides oocytes resources for in vitro fertilization and somatic cell nuclear transfer. Previous studies proved that SIRT2, a member of the sirtuin family, plays a role in oocyte meiosis, but its role in sheep oocyte maturation and its regulating mechanism remains unknown. Firstly, we confirmed the role of Sirt2 in sheep oocytes maturation by supplementation of SIRT2 inhibitor and activator. To further explore the specific mechanism, we performed knockdown of Sirt2 in granulosa cells and then cocultured them with oocytes. Moreover, we determined the effects of Sirt2 on granulosa cell oxidative apoptosis, cell migration, and diffusion, and examined its effects on granulosa cell mitochondrial function, mitophagy, and steroid hormone levels. The results showed that supplementation of SIRT2 inhibitor decreased the oocytes maturation rate (69.28% ± 1.28 vs. 45.74% ± 4.74, p < 0.05), while resveratrol, a SIRT2 activator, increased its maturation rate (67.44% ± 1.68 vs. 78.52 ± 1.28, p < 0.05). Knockdown of Sirt2 in sheep granulosa cells also reduced the oocytes maturation rate (47.98% ± 1.43 vs. 33.60% ± 1.77, p < 0.05), and led to decreased cell migration and expansion ability, oxidative apoptosis, abnormal mitochondrial gene expression, decreased mitochondrial membrane potential and ATP level, and increased mitophagy level. Overexpression of Sirt2 improved mitochondrial membrane potential and ATP level and improved mitochondrial function. Furthermore, we found that Sirt2 knockdown in granulosa cells promotes the secretion of P4 through regulating p-ERK1/2. In conclusion the present study showed that SIRT2 is critical for sheep oocyte maturation through regulating the function of ovarian granulosa cells, especially affecting its mitochondrial function.

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.