Excessive Daytime Sleepiness in Parkinson's Disease is Related to Functional Abnormalities in the Left Angular Gyrus.

PURPOSE: Excessive daytime sleepiness (EDS) is a common non-motor symptom in Parkinson's disease (PD), but its neuropathology remains elusive. Our goal is to explore the potential neural substrates of EDS in a large sample of individuals with PD. METHODS: We recruited 48 PD patients with and 87 PD patients without EDS. We used resting-state functional magnetic resonance imaging to compare amplitudes of low-frequency fluctuations (ALFF) between the two groups. We also explored functional connectivity (FC) between the entire brain and regions where ALFF differed between the two groups as well as FC between selected regions of interest. Age, Part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) score and use of dopamine receptor agonists were treated as covariates in the comparisons. RESULTS: EDS was associated with significantly lower ALFF in the left angular gyrus, and ALFF in this region correlated negatively with score on the Epworth Sleepiness Scale in patients with PD. EDS was also associated with significantly lower FC between the left angular gyrus and right cerebellum, based on seed-to-voxel and inter-ROI analyses. CONCLUSION: Our results suggest that EDS in PD patients is associated with reduced spontaneous neural activity in the left angular gyrus and with reduced FC between the left angular gyrus and cerebellum. These findings may help understand and treat EDS in PD.

Correlation of matrix metalloproteinase 3 and matrix metalloproteinase 9 levels with non-motor symptoms in patients with Parkinson's disease.

Objective: Matrix metalloproteinases (MMPs) are essential for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. MMPs have been widely studied in acute brain diseases. However, the relationship with Parkinson's disease (PD) remains unclear. The purpose of this study was to evaluate the serum MMP3 and MMP9 levels of PD patients and analyze their correlation with non-motor symptoms. Methods: In this cross-sectional study, we recruited 73 patients with idiopathic PD and 64 healthy volunteers. Serum MMP3 and MMP9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with PD were assessed for non-motor symptoms using the Non-motor Symptoms Scale (NMSS) and Parkinson's disease sleep scale (PDSS) and Mini Mental State Examination (MMSE). Results: Serum MMP3 levels were significantly decreased in PD patients, predominantly those with early-stage PD, compared with controls [12.56 (9.30, 17.44) vs. 15.37 (11.33, 24.41) ng/ml; P = 0.004], and the serum MMP9 levels of PD patients were significantly higher than those of healthy controls [522 (419, 729) vs. 329 (229, 473) ng/ml; P < 0.001]. MMP3 levels were positively correlated with the NMSS total score (r = 0.271, P = 0.020) and the single-item scores for item six, assessing the gastrointestinal tract (r = 0.333, P = 0.004), and there was an inverse correlation between serum MMP3 levels and PDSS score (r = -0.246, P = 0.036); meanwhile, MMP9 levels were positively correlated with the NMSS total score (r = 0.234, P = 0.047), and higher serum MMP9 levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [658 (504, 877) vs. 502 (397, 608) ng/ml, P = 0.008]. Conclusion: The serum MMP3 level of PD patients (especially early-stage patients) was significantly lower than that of the healthy control group, and the MMP9 level was significantly higher than that of the healthy control group. MMP3 and MMP9 levels correlate with sleep disturbance and cognitive function in PD patients, respectively.

Differences in neuroanatomy and functional connectivity between motor subtypes of Parkinson's disease.

Background: The "postural instability/gait difficulty" (PIGD) and "tremor-dominant" (TD) motor subtypes of Parkinson's disease (PD) differ in their clinical manifestations. The neurological basis of these differences is unclear. Methods: We performed voxel-based morphometric analysis and measured amplitudes of low-frequency fluctuation (ALFF) on 87 PIGD patients and 51 TD patients. We complemented this neuroanatomical comparison with seed-to-voxel analysis to explore differences in functional connectivity. Results: The PIGD group showed significantly smaller gray matter volume in the medial frontal gyrus (mainly on the right side) than the TD group. Across all patients, gray matter volume in the medial frontal gyrus correlated negatively with severity of PIGD symptoms after controlling for age (r = -0.250, p = 0.003), but this correlation was not observed in separate analyses of only PIGD or TD patients. The PIGD group showed greater functional connectivity of the right superior frontal gyrus with the left lingual gyrus, right lateral occipital cortex, and right lingual gyrus. ALFF did not differ significantly between the two groups. Conclusion: Postural instability/gait difficulty may be associated with smaller gray matter volume in medial frontal gyrus than TD, as well as with greater functional connectivity between the right superior frontal gyrus and occipital cortex. These results may help explain the clinical differences between the two motor subtypes of PD.

Structural and functional abnormalities in Parkinson's disease based on voxel-based morphometry and resting-state functional magnetic resonance imaging.

OBJECTIVE: To explore differences in gray matter volume (GMV) and white matter volume (WMV) between patients with Parkinson's disease (PD) and healthy controls, and to examine whether the structural abnormalities correlate with functional abnormalities. METHODS: T1-weighted magnetic resonance imaging and resting-state functional magnetic resonance imaging (fMRI) were performed on 180 patients with PD and 58 age- and sex-matched healthy controls. We used voxel-based morphometry (VBM) to compare GMV and WMV between groups, and resting-state fMRI to compare amplitudes of low-frequency fluctuations (ALFF) in the structurally abnormal brain regions. RESULTS: Structural neuroimaging showed smaller whole-brain GMV, but not WMV, in patients. Furthermore, VBM revealed smaller GMV in the right superior temporal gyrus (STG) and left frontotemporal space in patients, after correction for multiple comparisons. Patients also showed significantly higher ALFF in the right STG. GMV in the right STG and left frontotemporal space in patients correlated negatively with age and scores on Part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale, but not with PD duration. CONCLUSIONS: Structural atrophy in the frontotemporal lobe may be a useful imaging biomarker in PD, such as for detecting disease progression. Furthermore, this structural atrophy appears to correlate with enhanced spontaneous brain activity. This study associates particular structural and functional abnormalities with PD neuropathology.

Differences in Brain Activity Between Dopa-Responsive and -Unresponsive Pain in Parkinson's Disease.

INTRODUCTION: Pain in Parkinson's disease is poorly understood, and most patients with pain do not respond to dopaminergic drugs. We aimed to explore the mechanisms of dopa-responsive and -unresponsive pain by comparing such patients against patients without pain in terms of neural activity and functional connectivity in the brain. METHODS: We prospectively examined 31 Parkinson's patients with dopa-responsive pain, 51 with dopa-unresponsive pain and 93 without pain using resting-state functional magnetic resonance imaging. Neural activity was assessed in terms of the amplitude of low-frequency fluctuation, while functional connectivity was assessed based on analysis of regions of interest. RESULTS: Patients with dopa-unresponsive pain showed significantly higher amplitude of low-frequency fluctuation in the right parahippocampal/lingual region than patients with no pain. However, there was no amplitude difference between the dopa-responsive pain group and the no pain group. Patients with dopa-unresponsive pain also differed significantly from patients with no pain in their functional connections between the superior temporal gyrus and other areas of cerebral cortex, between amygdala and thalamus and between the amygdala and putamen. Patients with dopa-responsive pain differed significantly from patients with no pain in their functional connections between temporal fusiform cortex and cerebellum, between precentral gyrus and temporal fusiform cortex and between precentral gyrus and cerebellum. CONCLUSIONS: Regional neural activity and functional connectivity in the brain differ substantially among Parkinson's patients with dopa-unresponsive pain, dopa-responsive pain or no pain. Our results suggest that dopa-responsive and -unresponsive pain may arise through different mechanisms, which may help guide the development of targeted therapies.

Resting-state functional magnetic resonance imaging in patients with Parkinson's disease with and without constipation: a prospective study.

PURPOSE: The etiology of constipation in Parkinson's disease is largely unknown. The aim of this study was to explore changes in regional neural activity and functional connections associated with constipation in a large cohort of individuals with Parkinson's disease. METHODS: We prospectively recruited 106 patients with Parkinson's disease with constipation and 73 patients with Parkinson's disease without constipation. We used resting-state functional magnetic resonance imaging for the first time to measure differences in regional neural activity and functional connections between the two patient groups. RESULTS: Patients with constipation showed significantly higher amplitude of low-frequency fluctuation than patients without constipation in the right dorsal pons extending into the cerebellum and in the right insula. The two types of patients also showed substantial differences in functional connections linking the superior temporal gyrus, particularly the right superior temporal gyrus, with multiple brain regions. CONCLUSION: Regional neural activity and functional connectivity in the brain differ substantially between patients with Parkinson's disease with or without constipation. These findings provide a foundation for understanding the pathophysiology of constipation in Parkinson's disease and for identifying therapeutic targets.

LncRNA PVT1 promotes proliferation and invasion through enhancing Smad3 expression by sponging miR-140-5p in cervical cancer.

Background Cervical cancer is one of the most frequent malignancies among females worldwide. Increasing evidence have indicated the participation of long noncoding RNAs (lncRNAs) in the progression and metastasis of cervical cancer. Our present study was conducted to explore the effects of lncRNA plasmacytoma variant translocation 1 (PVT1) on the progression of cervical cancer and the underlying mechanisms. Materials and methods Expressions of PVT1, miR-140-5p and Smad3 in cervical cancer cell lines were detected by qRT-PCR and western blotting. Bioinformatics analysis and luciferase assays were used to elucidate the potential correlations between PVT1, miR-140-5p and Smad3. The roles of PVT1 on the progression of cervical cancer cells were determined by transfecting sh-RNA through series function assays such as colony formation assay, wound healing assay, transwell assay. Results PVT1 and Smad3 were upregulated, and miR-140-5p was downregulated in cervical cancer cells. PVT1 could bind directly with miR-140-5p, and Smad3 was a downstream target of miR-140-5p. Inhibition of PVT1 could enhance expression of miR-140-5p, inhibit the expression of Smad3, significantly inhibited the proliferation, migration, invasion in cervical cancer cells. While transfection of miR-140-5p inhibitor could partially reverse the above changes in cervical cancer cells. Conclusions The results revealed that PVT1 could promote the proliferation and metastasis via increasing the Smad3 expression by sponging miR-140-5p, which might be a promising prognostic and therapeutic target for cervical cancer.