Subject(s)
Ascorbic Acid , Parkinson Disease , Diet , Humans , Parkinson Disease/epidemiology , Vitamin E , VitaminsABSTRACT
Multiple microRNAs (miRs) have also been implicated in ischemic brain injury. This research intended to probe the regulatory function and the mechanism of miR-15a on the ischemic brain injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in neurons of rats. The OGD/R model was established with the cortical neurons separated from rats. After transfection with miR-15a mimic negative control (NC), miR-15a mimic, miR-15a inhibitor NC and miR-15a inhibitor, the OGD/R-induced apoptosis were detected. Using bioinformatic softwares including TargetScan, miRanda, and miRWalk to predict the underlying targets of miR-15a, and the binding of miR-15a with brain-derived neurotrophic factor (BDNF) were validated with double-fluorescein reporter assay system. The expression levels of BDNF mRNA and protein were detected with qRT-PCR and western blot. The effect of miR-15a on PI3K/AKT pathway in neurons submitted to OGD/R was also investigated. The findings showed that miR-15a may mediate the apoptosis of neurons submitted to OGD/R, and lower expression of Bcl-2 and higher expression of Bax and cleaved caspase-3 were observed. BDNF was screened as the candidate target, and the direct binding of miR-15a with 3'-UTR of BDNF were verified. Further research showed that miR-15a downregulated the expression of BDNF mRNA and protein, thus exerted negative regulatory effect on the OGD/R injury. PI3K/AKT pathway may be related to the regulatory effect of miR-15a. Our findings contribute to uncovering novel pathogenesis for ischemic brain injury.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Glucose/metabolism , MicroRNAs/metabolism , Neurons/metabolism , Oxygen/metabolism , Animals , Apoptosis/genetics , Apoptosis/physiology , Blotting, Western , Cell Survival/genetics , Cell Survival/physiology , Computational Biology , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
Objective: We aimed to assess the possible relations between serum levels of macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory response, and benign paroxysmal positional vertigo (BPPV) risk and BPPV recurrence events.Methods: In the present study, 154 patients with BPPV, and 100 age-and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio-vestibular test battery including the Dix-Hallpike maneuver and supine roll test. In the BPPV group, measurements of MIF levels were repeated 1â month after the vertigo attack. The patients were also divided into the recurrence group and the nonrecurrence group in the 1-year follow-up.Results: The serum levels of MIF in patients with BPPV were higher than in those controls (13.9[interquartile range {IQR}, 8.9-18.4] ng/ml vs. 9.8[7.8-11.8]; P<0.001). As a continuous variable, MIF was associated with increased risk of BPPV (odds ratio [OR] 1.21, 95% confidence interval [CI]: 1.11-1.39; P=0.004) in multiple regression analyses. Recurrent attacks of BPPV were reported in 35 patients, and those patients had higher levels of MIF than those patients were not recurrence (18.0[IQR, 13.6-22.2] ng/ml vs. 12.6[9.3-16.8] ng/ml). In multivariate models comparing the second (Q2), third (Q3) and fourth(Q4) quartiles against the first (Q1) quartile of MIF, levels of MIF in Q4 were associated with recurrent BPPV, and the odds were increased by approximately 305% (OR = 4.05; 95%CI: 1.65-15.44; P=0.009).Conclusions: Elevated MIF is positively correlated with BPPV risk and BPPV recurrence events, requiring further efforts to clarify the exact mechanism.
