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This study aimed to identify possible therapeutic targets involved in sleep deprivation (SD) risks. GSE77393 data set was acquired from Gene Expression Omnibus database. Functional analysis and protein-protein interaction (PPI) analysis were used to extract the differentially expressed genes (DEGs) between two SD samples and control samples. Moreover, submodule network with the same function was further extracted and the functional enrichment analysis of corresponding genes was carried out. Afterward, the transcriptional regulation analysis and drug-gene interaction were also carried out to identify the essential genes associated with SD susceptibility. Totally, 121 DEGs, including 90 consistently upregulated DEGs and 31 downregulated DEGs, were screened and the results of functional analysis indicated that upregulated genes were related to learning or memory and response to drug, whereas downregulated DEGs were mainly responsible for response to UV and cell differentiation. Moreover, PPI network and submodule analysis revealed that many key genes (FOS and BDNF) were hub genes and the KEGG enrichment analysis found that these genes such as FOS and BDNF were considerably enriched in pathways such as MAPK signaling pathway, HTLV-I infection, and Hepatitis B. In addition, two genes (FOS and BDNF) with a higher degree were found to be key regulators and play important roles in the transcriptional regulator network and drug-gene interactions, suggesting that these two genes were associated with SD development. FOS and BDNF might be served as the potential targets for SD treatment.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Marcadores Genéticos , Proteínas Proto-Oncogênicas c-fos/genética , Privação do Sono/genética , Biologia Computacional , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Mapas de Interação de ProteínasRESUMO
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.
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BACKGROUND: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. METHODS: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. RESULTS: No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (ß = 0.552, P < 0.001) and RBD (ß = 0.433, P < 0.001) as predictors of higher tonic EMG density. CONCLUSION: Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.
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Eletromiografia/métodos , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/fisiopatologia , Polissonografia , Estudos RetrospectivosRESUMO
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD. METHODS: The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis. RESULTS: Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results. CONCLUSIONS: When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.
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Disfunção Cognitiva/etiologia , Doença de Parkinson/complicações , Transtorno do Comportamento do Sono REM/complicações , Idoso , Idoso de 80 Anos ou mais , Humanos , Modelos Logísticos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The aim of the present study was to investigate the relationship between rapid eye movement (REM) sleep without atonia (RWA) and Parkinson's disease (PD) progression. METHODS: We quantified tonic and phasic RWA by performing polysomnography in 198 PD patients. We then correlated the extent of RWA with clinical patient characteristics. RESULTS: PD patients were categorized into quartiles of tonic and phasic RWA. We found that patients with more RWA tended to be older and have longer PD duration, a greater likelihood of REM sleep behavior disorder (RBD), more advanced Hoehn & Yahr (H&Y) stage, a higher dose of parkinsonian medication, poorer cognitive performance, worse quality of life, and more severe sleep disturbance. After adjusting for age, sex, and PD duration, patients in the highest two RWA quartile were more likely to have severe PD (H&Y stage ⩾ 3.0) than those in the lowest RWA quartile. CONCLUSIONS: These findings provide evidence that RWA, especially with regard to tonic muscle activity, is associated with PD severity. SIGNIFICANCE: Further studies are warranted to determine the importance and utility of assessing RWA to evaluate sleep in PD patients.