Project description:The aim of this study was to investigate the clinical characteristics and underlying pathogenesis of episodic vestibular syndrome (EVS) with hyperventilation-induced downbeat nystagmus (HV-DBN).
Project description:To investigate which miRNAs regulate the vestibular compensation after unilateral vestibular deafferentiation (UVD), we have performed microarray for miRNAs as a discovery platform. UVD induces breakdown of the activity of ipsilesional vestibular nuclei and an unbalance of activity between bilateral vestibular nuclei. Vestibular compensation is a course of rebalancing of activities of bilateral vestibular nuclei. It takes place mainly in medial vestibular nucleus. This study was performed using seven week-old-male Sprague–Dawley rats. Based on our previous experiment about vestibular compensation course, we set two time points for harvesting medial vestibular nuclei: 4hr and 4 days after unilateral vestibular deafferentiation. Twenty four animals were divided into two experimental groups: UVD group undergoing UVD at left side (n = 12); and SO group undergoing sham operation (SO) at left side (n=12). Six animals of each group were anesthetized deeply and euthanized at 4 hr or 4 days after surgery, respectively. Medial vestibular nucleus at left side was harvested. Medial vestibular nucleus from three animals became one sample for microarray. Sequentially two samples were obtained for each time point in one group. Microarray for miRNAs was performed using the Agilent Rat miRNA Microarray 8x15K platforms. Considering the fold change of normalized signal intensities between two time points in UVD group and between UVD and SO groups at the same time, miR-31a-5p, 133a-3p, 133b-3p, 204-5p, 206-3p, 218a-5p, 219a-5p, 221-3p and 497-5p were selected as the candidate miRNAs. This result was validated by quantitative reverse transcription-PCR.
Project description:Vestibular schwannomas are intracranial tumors that affects unilateral and sporadically or bilateral when is associated to Neurofibromatosis type 2 syndrome. The hallmark of the disease is the biallelic inactivation by NF2 gene mutation or LOH of chromosome 22q, where this gene harbors. In this work, we used Infinium HumanMethylation 450K BeadChip microarrays in a series of 36 vestibular schwannomas, 4 non-vestibular schwannomas and 5 healthy nerves. Our results shows a trend to hypomethylation in schwannomas. Furthermore, HOX genes, located at 4 clusters in the genome, displayed hypomethylation in numerous CpG sites in vestibular but not in non-vestibular schwannomas. Additionally, several microRNA and protein-coding genes were found hypomethylated at promoter regions and confirmed by expression analysis; including miRNA-199a1, miRNA-21, MET and PMEPA1. We also detected methylation patterns that might be involved in alternative transcripts of several genes such as NRXN1 or MBP; that would increase the complexity of methylation-expression. Overall, our results shows specific epigenetic signatures in several coding genes and microRNA that could be used in the finding of potential therapeutic targets.
Project description:Vestibular schwannomas are intracranial tumors that affects unilateral and sporadically or bilateral when is associated to Neurofibromatosis type 2 syndrome. The hallmark of the disease is the biallelic inactivation by NF2 gene mutation or LOH of chromosome 22q, where this gene harbors. In this work, we used Infinium HumanMethylation 450K BeadChip microarrays in a series of 36 vestibular schwannomas, 4 non-vestibular schwannomas and 5 healthy nerves. Our results shows a trend to hypomethylation in schwannomas. Furthermore, HOX genes, located at 4 clusters in the genome, displayed hypomethylation in numerous CpG sites in vestibular but not in non-vestibular schwannomas. Additionally, several microRNA and protein-coding genes were found hypomethylated at promoter regions and confirmed by expression analysis; including miRNA-199a1, miRNA-21, MET and PMEPA1. We also detected methylation patterns that might be involved in alternative transcripts of several genes such as NRXN1 or MBP; that would increase the complexity of methylation-expression. Overall, our results shows specific epigenetic signatures in several coding genes and microRNA that could be used in the finding of potential therapeutic targets.
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
Project description:Vestibular nuclei (VN) are critical for the processing of movement input, and motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify diferent markers of glutamatergic vestibular neuronal populations using the RiboTag apparoach.
Project description:Pooled Immunoflourescent guided laser capture microdisection of calyceal vestibular primary afferent neurons (calretinin positive) and dimorphic-bouton vestibular primary afferent neurons (calretinin negative) were used for microarray expression profiling. Transcription analysis of each of these biologically diverse pools was completed.
Project description:Microarray analysis was used to examine the expression of genes upregulated or downregulated in the ipsilateral vestibular nucleus at 1 and 7 days following unilateral labyrinthectomy. Changes in gene expression during the chronic phase of vestibular compensation following unilateral labyrinthectomy in rats Three conditioned experiment: nl:control with sham operation, 1day:1day after labyrninthectomy, 7day:7day after labyrinthectomy