Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice.
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ABSTRACT:
SUBMITTER: Ito T
PROVIDER: S-EPMC6896078 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL). Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0-4 via electrodes inserted subcutaneously next to both bony labyrinths. Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p < 0.001 in both amount of circling and total path length) and 7 (p < 0.01 in amount of circling and p < 0.001 in total path length, Mann-Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p < 0.001), 7 (p < 0.001), and 14 (p < 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p < 0.001 at POD 14). Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.
| S-EPMC8446527 | biostudies-literature
Project description:Prosaposin, a precursor of four glycoprotein activators (saposin A, B, C and D) for lysosomal hydrolases, has previously been shown to be important for normal adult cochlear innervation and the maintenance of normal hearing. In these studies, we now investigate prosaposin in normal vestibular epithelium and the functional impairment of balance caused by prosaposin ablation. In normal mice, prosaposin is localized to all 3 vestibular end-organs (ampullae, saccule, and utricle) and Scarpa's ganglion by RT-PCR, Western blot analysis and immunofluorescence. Ablation of prosaposin function caused severe vestibular dysfunction on a battery of behavioral tasks. Histologically, the KO mice demonstrated an exuberant cellular proliferation below the vestibular hair cells with disruption of the supporting cells. Electron microscopy further demonstrated inclusion bodies and cellular proliferation disturbing the normal neuroepithelial structure of the vestibular end-organs. Lastly, immunofluorescence (neurofilament 200 and synaptophysin) staining suggests that this cellular proliferation corresponds to afferent and efferent neuronal overgrowth. These data suggest that prosaposin plays a role not only in the maintenance of normal hearing but also an important role in the neuronal maturation processes of the vestibular sensory epithelium and the maintenance of normal vestibular system function.
| S-EPMC3312039 | biostudies-literature
Project description:Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design.White cases (n=137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n=126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes.Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p <or= 0.03). MDR analysis revealed a three-gene combination, consisting of NOS3 (p.Glu298Asp), GSTZ1 (p.Lys32Glu), and GSTP1 (p.Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p=0.009).The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction.
| S-EPMC2581796 | biostudies-literature
Project description:Mutations in the human cadherin 23 (CDH23) gene cause deafness, neurosensory, autosomal recessive 12 (DFNB12) nonsyndromic hearing loss or Usher syndrome, type 1D (characterized by hearing impairment, vestibular dysfunction, and visual impairment). Reported waltzer mouse strains each harbor a Cdh23-null mutation and present with hearing loss and vestibular dysfunction. Two additional Cdh23 mouse mutants, salsa and erlong, each carry a homozygous Cdh23 missense mutation and have progressive hearing loss. We report the identification of a novel mouse strain, jera, with inherited hearing loss caused by an N-ethyl-N-nitrosourea-induced c.7079T>A mutation in the Cdh23 gene. The mutation generates a missense change, p.V2360E, in Cdh23. Affected mice have profound sensorineural deafness, with no vestibular dysfunction. The p.V2360E mutation is semidominant because heterozygous mice have milder and more progressive hearing loss in advanced age. The mutation affects a highly conserved Ca(2+)-binding motif in extracellular domain 22, thought to be important for Cdh23 structure and dimerization. Molecular modeling suggests that the Cdh23(V2360E/V2360E) mutation alters the structural conformation of the protein and affects Ca(2+)-binding properties. Similar to salsa mice, but in contrast to waltzer mice, hair bundle development is normal in jera and hearing loss appears to be due to the loss of tip links. Thus, jera is a novel mouse model for DFNB12.
| S-EPMC3157152 | biostudies-literature
Project description:The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM at each PLD compared to pre-lesion status were performed. After lesion, augmented metabolic activation by GVS was detected in cerebellum, mainly contralateral, and in contralateral subcortical structures such as superior colliculus, while diminished activation was observed in ipsilateral visual, entorhinal, and somatosensory cortices, indicating compensatory processes in the non-affected sensory systems of the unlesioned side. The changes in rCGM observed after lesion resembled alterations observed in patients suffering from unilateral thalamic infarction and may be interpreted as brain plasticity mechanisms associated with vestibular compensation and substitution. The second set of experiments aimed at the connections between cortical and subcortical vestibular regions and their neurotransmitter systems. Neuronal tracers were injected in regions processing vestibular and somatosensory information. Injections into the anterior cingulate cortex (ACC) or the primary somatosensory cortex (S1) retrogradely labeled neuronal somata in ventral posteromedial (VPM), posterolateral (VPL), ventrolateral (VL), posterior (Po), and laterodorsal nucleus, dorsomedial part (LDDM), locus coeruleus, and contralateral S1 area. Injections into the parafascicular nucleus (PaF), VPM/VPL, or LDDM anterogradely labeled terminal fields in S1, ACC, insular cortex, hippocampal CA1 region, and amygdala. Immunohistochemistry showed tracer-labeled terminal fields contacting cortical neurons expressing the ?-opioid receptor. Antibodies to tyrosine hydroxylase, serotonin, substance P, or neuronal nitric oxide-synthase did not label any of the traced structures. These findings provide evidence for opioidergic transmission in thalamo-cortical transduction.
| S-EPMC7256190 | biostudies-literature
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.
2018-02-27 | GSE93111 | GEO
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
2011-11-16 | E-GEOD-32437 | biostudies-arrayexpress
Project description:Mouse N-ethyl-N-nitrosourea (ENU) mutagenesis has generated many useful animal models for human diseases. Here we describe the identification of a novel ENU-induced mouse mutant strain Turner (Tur) that displays circling and headtossing behavior and progressive hearing loss. Tur/Tur homozygous animals lack Preyer and righting reflexes and display severe headtossing and reaching response defect. We mapped the Tur mutation to a critical region of 11 cM on chromosome 9 that includes myosin VI. Direct sequence analysis revealed a c.820A>T substitution in exon 8 of the Myo6 gene that changes amino acid Asn200 to Ile (p.N200I) in the motor domain. Analysis of inner ear hair cells by immunohistochemistry, scanning electron microscopy and histology revealed degeneration of hair cells in the inner ear and structural malformation of the stereocilia in the cochlea of Turner homozygous mutant mice. Our data indicate that this novel mouse strain provides a useful model for future studies on the function of myosin VI in mammalian auditory and non-auditory systems and in human syndromes.
| S-EPMC4865150 | biostudies-literature
Project description:Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2'-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h ~ 7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.
| S-EPMC8810063 | biostudies-literature
Project description:A/J mice develop progressive hearing loss that begins before 1 month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated that this strain also develops early onset vestibular dysfunction and has otoconial deficits. The purpose of this study was to characterize the vestibular dysfunction and macular structural pathology over the lifespan of A/J mice. Vestibular function was measured using linear vestibular evoked potentials (VsEPs). Macular structural pathology was evaluated using light microscopy, scanning electron microscopy, transmission electron microscopy, confocal microscopy and Western blotting. Individually, vestibular functional deficits in mice ranged from mild to profound. On average, A/J mice had significantly reduced vestibular sensitivity (elevated VsEP response thresholds and smaller amplitudes), whereas VsEP onset latency was prolonged compared to age-matched controls (C57BL/6). A limited age-related vestibular functional loss was also present. Structural analysis identified marked age-independent otoconial abnormalities in concert with some stereociliary bundle defects. Macular epithelia were incompletely covered by otoconial membranes with significantly reduced opacity and often contained abnormally large or giant otoconia as well as normal-appearing otoconia. Elevated expression of key otoconins (i.e., otoconin 90, otolin and keratin sulfate proteoglycan) ruled out the possibility of reduced levels contributing to otoconial dysgenesis. The phenotype of A/J was partially replicated in a consomic mouse strain (C57BL/6J-Chr 17(A/J)/NaJ), thus indicating that Chr 17(A/J) contained a trait locus for a new gene variant responsible to some extent for the A/J vestibular phenotype. Quantitative trait locus analysis identified additional epistatic influences associated with chromosomes 1, 4, 9 and X. Results indicate that the A/J phenotype represents a complex trait, and the A/J mouse strain presents a new model for the study of mechanisms underlying otoconial formation and maintenance.
| S-EPMC4374992 | biostudies-other