G2019S LRRK2 Mutation Enhances MPP+-Induced Inflammation of Human Induced Pluripotent Stem Cells-Differentiated Dopaminergic Neurons.

Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to mimic human diseases of related cell types, but it is unclear whether they can successfully mimic age-related diseases such as Parkinson's disease (PD). We generated iPSCs lines from three patients with familial PD associated with the G2019S mutation in the LRRK2 gene and one age-matched healthy individual (control). During long-term culture, dopaminergic (DA) neurons differentiated from iPSCs of G2019S LRRK2 PD patients exhibited morphological changes, including a reduced number of neurites and neurite arborization, which were not evident in DA neurons differentiated from control iPSCs. To mimic PD pathology in vitro, we used 1-methyl-4-phenylpyridium (MPP+) to damage DA neurons and found that DA neurons differentiated from patients with G2019S LRRK2 mutation significantly reduced the survival rate and increased apoptosis compared with the controls. We also found that the mRNA level of inflammatory factors [interleukin (IL)-1ß, tumor necrosis factor-α, cyclooxygenase-2, IL-6, and inducible NO synthase] with G2019S LRRK2 mutation were higher than control group after exposure to MPP+. Our study provides an in vitro model based on iPSCs that captures the patients' genetic complexity and investigates the pathogenesis of familial PD cases in a disease-associated cell type.

Echogenicity Changes in Brainstem Raphe Detected by Transcranial Parenchymal Sonography and Clinical Characteristics in Parkinson's Disease.

Background: Decreased brainstem raphe (BR) echogenicity detected by transcranial parenchymal sonography (TCS) is associated with depression in psychiatric and neurologic diseases. However, previous studies focusing on the relationship between motor and non-motor symptoms and echogenicity changes in BR in patients with PD yielded controversial results. Objectives: To investigate the relationship between echogenicity changes in BR detected by TCS and motor and a series of non-motor symptoms in patients with PD. Methods: Consecutive PD patients were recruited from the Second Affiliated Hospital of Soochow University. Demographic information and Motor and non-motor symptoms for all subjects were collected. TCS was used to detect the echogenicity changes in BR in PD patients. Results: One hundred and thirty-five consecutive patients with PD were enrolled in the study. The BR abnormal rate was significantly higher in PD patients with anxiety (p = 0.003) or depression (p = 0.022) than patients without. Spearman correlation analyses showed that Hamilton Rating Scale for Depression(HRSD) (r = 0.274, p = 0.002) and Parkinson's Disease Questionnaire 39-item(PDQ-39) (r = 0.208, p = 0.034) scores were positively correlated with abnormal BR echogenicity. Multivariate logistic regression analyses showed that HRSD and HAMA scores were associated with BR hypoechogenicity, the corresponding odds ratios (confidence intervals) were 1.07 (95% CI, 1.01-1.13) and 1.10(1.01-1.18), respectively. However, the PDQ-39 score was not associated with BR hypoechogenicity. Conclusion: The abnormal reduction in BR echogenicity detected by TCS is associated with depression and anxiety, but not motor symptoms in PD patients.

Analysis of nocturnal hypokinesia and sleep quality in Parkinson's disease.

Nocturnal hypokinesia/akinesia and sleep disorder are believed to be common in Parkinson's disease (PD), but are often underestimated. To date, only a few studies have focused on nocturnal symptoms related to motor function and sleep quality in PD patients, and the assessments were based mainly on the subjective descriptions of the patients. In this study, we assessed the relationships between motor symptoms and sleep quality in 29 PD patients (17 PD patients reporting impaired bed mobility (IBM) and 12 patients without IBM). All the participants were monitored using multisite inertial sensors and polysomnography in sleep-monitoring rooms for whole night. Compared with PD-IBM patients, PD+IBM patients tended to have fewer turning-over episodes and smaller degree turns. Meanwhile, PD+IBM patients had worse Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scale (PDSS) scores, and less total sleep time (TST) than PD-IBM patients. Spearman correlation analyses found that the number of turning-over events showed negative correlations with disease duration (r = -0.378, P < 0.05) and Unified Parkinson's Disease Rating Scale (UPDRS) axial scores (r = -0.370, P < 0.05). Moreover, TST (r = 0.505, p < 0.05) and sleep efficiency (SE) (r = 0.473, p < 0.05) positively correlated with the number of turns in bed. Multivariate linear regression analyses showed that UPDRS axial scores and the number of turns were significantly associated with TST (both p < 0.05). In conclusion, the number of turns in bed and UPDRS axial scores were two significant factors affecting sleep quality. Multisite inertial sensors can be used to quantitatively evaluate nocturnal motor functions in PD patients.