RESUMO
OBJECTIVE: Perivascular spaces (PVS), components of the glymphatic system in the brain, have been known to be important conduits for clearing metabolic waste, and this process mainly increases during sleep. Sleep disruption might result in PVS dysfunction and cognitive impairment. In this study, we aim to explore whether MRI-visible enlarged perivascular spaces (EPVS) could be imaging markers to predict cognitive impairment in chronic insomnia patients. METHOD: We obtained data from 156 patients with chronic insomnia and 79 age-matched healthy individuals. Using T2-weighted MRI images, visible EPVS in various brain regions were measured and analyzed. The associations between EPVS numbers and cerebrospinal fluid (CSF) ß-amyloid 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) level in chronic insomnia patients were evaluated. RESULT: Our results showed that MRI-visible EPVS in the frontal cortex, centrum semiovale, basal ganglia, and hippocampus of chronic insomnia patients with impaired cognition (ICG) significantly increased than that in normal cognition (NCG) patients. The increased MRI-visible EPVS in the frontal cortex, centrum semiovale, and basal ganglia were also associated with the increased CSF Aß42, t-tau, and p-tau level in ICG patients. MRI-visible EPVS in the basal ganglia and centrum semiovale had high sensitivity and specificity in distinguishing ICG chronic insomnia patients from those with NCG. CONCLUSION: Our study indicated that MRI-visible EPVS in the basal ganglia and centrum semiovale might be valuable imaging markers to predict cognitive impairment in chronic insomnia patients. It will be meaningful to discern those cognitive decline patients in preclinical stage and take some measures to prevent disease progression. KEY POINTS: ⢠Increased MRI-visible EPVS were associated with the increased CSF Aß42, t-tau, and p-tau level in older chronic insomnia patients with impaired cognition.
Assuntos
Disfunção Cognitiva , Distúrbios do Início e da Manutenção do Sono , Idoso , Gânglios da Base , Biomarcadores , Cognição , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagemRESUMO
To explore the possible mechanism of weight loss in Parkinson's disease (PD). Bilateral injections of 6-hydroxydopamine (6-OHDA) into substantia nigra (SN) were performed to induce the PD model rats. The rotarod test, food intake, body weight, and interscapular brown adipose tissue (IBAT) weight were recorded 6 weeks postoperation. HE staining was performed to observe the morphology of multilocular adipose cells in IBAT. Immunohistochemistry and western blot were used to determine the protein levels of tyrosine hydroxylase (TH) in the SN, and the levels of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), phosphorylated-hormone sensitive lipase (p-HSL), HSL, TH, ß3-adrenergic receptor (ß3-AR), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in IBAT. After treatment with 6-OHDA for 6 weeks, 6-OHDA rats exhibited decreased TH expression in SN accompanied with shortened staying time on the rotating rod. This motor impairment paralleled with no significant alteration in body mass, IBAT weight, and food intake until the end of the experimental protocol. However, the decreasing diameter of the single fat vesicle in IBAT was observed in the 6-OHDA group. Meanwhile, compared with the control group, the protein expression of UCP1, PGC-1α, p-HSL, TH, ß3-AR, cAMP, and PKA in IBAT were increased significantly in the 6-OHDA group, whereas no obvious change in the expression of HSL. The present study suggested an increased energy expenditure and activation of the ß3-AR-cAMP-PKA signaling pathway in the IBAT after the destruction of the dopamine system in the SN of the rat.
Assuntos
Tecido Adiposo Marrom/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Metabolismo Energético/fisiologia , Doença de Parkinson Secundária/metabolismo , Receptores Adrenérgicos beta 3/metabolismo , Transdução de Sinais/fisiologia , Animais , Masculino , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Ratos , Ratos Sprague-DawleyRESUMO
MicroRNA375 (miR375) serves an important role in cancer development and growth. However, little is known about the role of miR375 in the regulation of oral squamous cell carcinoma (OSCC) metastasis and invasion. The present study measured the expression levels of miR375 in Tca8113, UM2, UM1 and CAL27 cell lines, using reverse transcriptionquantitative polymerase chain reaction. The results demonstrated that miR375 expression levels were significantly reduced in UM1 and CAL27 (highly metastatic) compared with Tca8113 and UM2 (less aggressive) OSCC cell lines. Furthermore, it was revealed that overexpression of miR375 suppressed the migration and invasion of UM1 cells. Based on a luciferase reporter assay, plateletderived growth factorA (PDGFA) was identified as a direct target gene of miR375. Additionally, overexpression of PDGFA significantly reversed the effect of miR375 on cell migration and invasion in UM1 cells. These data demonstrated that miR375 suppressed OSCC cell migration and invasion by targeting PDGFA, which may be a potential therapeutic target for the treatment of OSCC.