Opioid modulation of T-type Ca2+ channel-dependent neuritogenesis/neurite outgrowth through the prostaglandin E2/EP4 receptor/protein kinase A pathway in mouse dorsal root ganglion neurons.

Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E2 (PGE2) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE2 in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP4, but not EP2, receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca2+ channels (T-channels), that are responsible for window currents involving the sustained low-level Ca2+ entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE2/IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl2 and ascorbic acid that block Cav3.2, but not Cav3.1 or Cav3.3, T-channels. Morphine and DAMGO, µ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE2/IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or ß-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP4 receptor/PKA/Cav3.2 pathway is involved in the PGE2-induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain.

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

The prostaglandin E2/EP4 receptor/cyclic AMP/T-type Ca(2+) channel pathway mediates neuritogenesis in sensory neuron-like ND7/23 cells.

We investigated mechanisms for the neuritogenesis caused by prostaglandin E2 (PGE2) or intracellular cyclic AMP (cAMP) in sensory neuron-like ND7/23 cells. PGE2 caused neuritogenesis, an effect abolished by an EP4 receptor antagonist or inhibitors of adenylyl cyclase (AC) or protein kinase A (PKA) and mimicked by the AC activator forskolin, dibutyryl cAMP (db-cAMP), and selective activators of PKA or Epac. ND7/23 cells expressed both Cav3.1 and Cav3.2 T-type Ca(2+) channels (T-channels). The neuritogenesis induced by db-cAMP or PGE2 was abolished by T-channel blockers. T-channels were functionally upregulated by db-cAMP. The PGE2/EP4/cAMP/T-channel pathway thus appears to mediate neuritogenesis in sensory neurons.

[Sternomyelitis caused by delayed tracheal necrosis after thyroidectomy;treatment using muscle flap of petoralis major].

We experienced a rare case of delayed tracheal rupture after thyroidectomy for papillary thyroid cancer, and the infection causing sternomyelitis. A 69-year-old man presented subcutaneous emphysema after 6 days of total thyroidectomy with bilateral cervical and mediastinal dissection for lymph node metastases by adverse T sternotomy. He underwent tracheostomy on 10th postoperative day (POD), debridement of sternum on 14th POD, and implantation of skin-muscle flap using pectolaris major on 43th POD. The flap showed good adaptation and no infectious complications recurred, so that he could consequently receive closing procedure of tracheostomy on 94th POD.

Atypical soft tissue perineurioma in the tongue of a young girl.

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.

Unilateral vestibular deafferentation-induced changes in calcium signaling-related molecules in the rat vestibular nuclear complex.

Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca(2+) from those neurons and perhaps prevent cell damage following UVD.

Effects of fluvoxamine on anxiety, depression, and subjective handicaps of chronic dizziness patients with or without neuro-otologic diseases.

A prospective, open-label clinical trial was conducted for two aims: first, to evaluate the role of fluvoxamine, one of selective serotonin reuptake inhibitors, in the treatment of dizziness for the first time and to investigate its effective mechanisms. Second, to test the hypothesis that dizziness in patients without abnormal neuro-otologic findings would be induced by psychiatric disorders rather than by unnoticed neuro-otologic diseases. Nineteen patients with neuro-otologic diseases (Group I) and 22 patients in whom standard vestibular tests revealed no abnormal findings (Group II) were treated by fluvoxamine (200 mg/day) for eight weeks. Subjective handicaps due to dizziness using a questionnaire, anxiety and depressive symptoms measured with the Hospital Anxiety and Depression Scale (HADS), and stress hormones (vasopressin and cortisol) were examined before and 8 weeks after treatment. Overall, fluvoxamine decreased subjective handicaps of both Groups I and II. Fluvoxamine decreased HADS of only patients whose subjective handicaps were reduced (=responders) in both groups, suggesting that fluvoxamine was effective for dizziness via psychiatric action rather than a recovery of vestibular function through serotonergic activation. In non-responders of Group II, pre-treatment HADS was higher than in Group I non-responders and it was not decreased by the treatment, suggesting that dizziness of Group II non-responders was due to severe psychiatric disorders rather than unnoticed neuro-otologic diseases. Anxiety and depression components of HADS showed a good correlation at both pre- and post-treatment periods. No post-therapeutic decrease was observed in either vasopressin or cortisol even in responders, suggesting that dizziness was not the sole cause of stress in chronic dizziness patients. In conclusion, patients with or without physical neuro-otologic deficits who report chronic dizziness accompanied by anxiety and depression (as measured by HADS) showed improvements across a full range of subjective handicaps and psychological distress, while patients with physical neuro-otologic defects and minimal anxiety or depression did not benefit. The main causes of dizziness in patients without physical neuro-otologic findings were psychiatric disorders.

Hippocampal gene expression, serum cortisol level, and spatial memory in rats exposed to hypergravity.

BACKGROUND: Due to spatial disorientation reported in space, spatial memory and navigation performances could be more largely impaired by gravity changes. Hippocampus, a key structure for spatial memory, receives inputs from gravity-sensing otolith organs. OBJECTIVE: To determine the key molecules in the rat hippocampus that contribute to an adaptation to altered gravity in terms of spatial memory performance. METHODS: Gene expression of hippocampus and spatial memory after continuous two-weeks exposure to 2 G hypergravity (HG) were examined using a microarray analysis followed by real-time PCR methods and radial arm maze testing, respectively. Serum cortisol levels during HG load were measured as a stress marker. RESULTS: Accuracy to enter the correct arms in HG rats was significantly lower than that of controls, indicating an impaired spatial memory due to gravity changes. Microarray analysis followed by real-time PCR confirmed an upregulation of insulin like growth factor binding protein 2 (IGFBP2) gene. Serum cortisol level was the same level as controls at the last day of hypergravity, suggesting the adaptation to HG-induced stress. CONCLUSIONS: Given that the IGF systems are involved in neurotrophic and synaptic plasticity mechanisms, IGF system might contribute to the adaptation to altered gravity in terms of spatial memory.

Factors relating to the vertigo control and hearing changes following intratympanic gentamicin for intractable Ménière's disease.

OBJECTIVE: To look for factors relating to the vertigo control and hearing changes after intratympanic injections of gentamicin (GM). STUDY DESIGN: Prospective. SETTING: Tertiary referral medical center. PATIENTS: Twenty-eight patients with intractable Ménière's disease. INTERVENTIONS: Three intratympanic injections of GM (once per day for three consecutive days). MAIN OUTCOME MEASURES: Although five patients needed further GM injections or vestibular neurectomy because of poor control (Group I), 23 patients had their vertigo controlled for more than two years without further treatment (Group II). The number of vertigo spells per month, pure-tone audiometry, electrocochleography, caloric response, post-head shake nystagmus, and plasma vasopressin as a stress marker were examined. RESULTS: Before GM injections, there was no difference in the number of vertigo spells per month between Groups I and II. However, the hearing thresholds were higher in Group I. Hearing improvement, increase in percentage of canal paresis and induction of post-head shake nystagmus were observed after GM injections only in Group II. Even in the 11 patients who showed an improvement in hearing of more than 10 dB (hearing improvement group), percentage of canal paresis was increased after GM. More, premedication plasma vasopressin levels were lower in the hearing improvement group as compared with the hearing loss/no changes group. Four of eight patients became negative for dominant negative summating potential in electrocochleography after GM injections in the hearing improvement group. CONCLUSION: Our data indicate that the frequency of vertigo is not a key factor in the vertigo control after GM injections, that induction of vestibular damage in the injected ear is essential for the control of vertigo and this effect is mostly pronounced in patients with milder hearing loss, and that hearing improvement is not only a consequence of good vertigo control but also affected by the stress level before treatment.

Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

Factors predicting severe infections during chemotherapy in head and neck cancer patients.

CONCLUSIONS: The head and neck cancer patients with more co-morbidities and those dependent on tube feeding are at a high risk of severe infections during chemotherapy. Therefore, prophylaxis with colony-stimulating factors and/or antibiotics should be considered for those patients. OBJECTIVES: To investigate the risk factors for severe infection during chemotherapy in head and neck cancer patients. METHODS: A retrospective study was conducted of 129 patients with head and neck cancer who received taxane-based and platinum-based chemotherapy between 2008-2013. Logistic regression models were used to evaluate risk factors. RESULTS: Febrile neutropenia occurred in 50 patients out of the 129 (39%), severe infections occurred in 24 patients (19%), and bacteremia in two patients (2%). In univariate analysis, low serum albumin levels and tube feeding were significantly associated with severe infections (p = 0.015 and < 0.001, respectively). In multivariate analysis, the odds ratios for a higher modified Charlson co-morbidity index and tube feeding were 2.80 and 9.74, respectively. These two were independent predictive factors for severe infections (p = 0.020 and 0.001, respectively).

Impaired spatial learning after hypergravity exposure in rats.

Most astronauts experience spatial disorientation after exposure to weightlessness, indicating that constant gravity is utilized as a stable external reference during spatial cognition. We attempted to elucidate the role of constant gravity in spatial learning using a radial arm maze test on rats housed in a hypergravity environment (HG) produced by a centrifuge device. Male Wistar rats were kept in 2G linear acceleration for 2 weeks before the spatial learning task, which lasted for 10 days. The control rats were placed close to the centrifuge device but not exposed to hypergravity. Spatial learning was evaluated by the accuracy and the re-entry rate, which were the rate of correct arm entries and the rate of entries into the arms that they had already visited, respectively. Locomotor activity was measured by number of entries per minute. The number of baits the animal took per minute was also measured. The results showed that accuracy was significantly inferior and the re-entry rate was significantly higher in the HG rats than in the controls, suggesting that animals use a constant gravity as a stable external reference in spatial learning. However, these differences disappeared at 5 days later, indicating that the HG rats learned the spatial task more rapidly than the controls. Locomotor activity was higher in the HG rats and there was no difference in number of baits per minute between the HG and control animals. In conclusion, if one sensory cue necessary for spatial cognition is disturbed by gravity change, animals can subsidize with other sensory cues such as proprioceptive and motor efference copy signals through increased locomotor activities.

Paroxetine, a selective serotonin reuptake inhibitor, reduces depressive symptoms and subjective handicaps in patients with dizziness.

OBJECTIVE AND STUDY DESIGN: When treating dizzy patients, the psychiatric aspect should be carefully addressed regardless of whether a well-defined organic disease is present. In this prospective study, we aimed to elucidate the role of paroxetine, a selective serotonin reuptake inhibitor, in the treatment of dizziness. SETTING AND PATIENTS: Forty-seven patients who complained of dizziness were treated with 20 mg of paroxetine per day. The depressive state of the patient was evaluated by the Zung Self-Rating Depression Scale (SDS). Treatment outcomes were measured with self-assessment of subjective handicaps in daily life using a dizziness and unsteadiness questionnaire. The questionnaire consisted of five factors related to emotional or bodily dysfunction that could be affected by dizziness. Changes in Self-Rating Depression Scale scores and subjective handicaps were assessed at 4 and 8 weeks after the start of paroxetine. RESULTS: In patients having well-defined organic diseases with high Self-Rating Depression Scale scores, paroxetine improved all five subjective handicap factors as well as Self-Rating Depression Scale scores. The decline in Self-Rating Depression Scale scores showed a significant correlation with improvement of subjective handicaps, which was related to emotional problems but not factors related to bodily dysfunction. Paroxetine was also effective for an improvement of factors related to emotional problems and Self-Rating Depression Scale scores in patients not having organic diseases but with high Self-Rating Depression Scale scores. In patients either with or without organic diseases with low Self-Rating Depression Scale scores, paroxetine had no effect on any subjective handicap factors and Self-Rating Depression Scale scores. CONCLUSION: In the treatment of dizzy patients, paroxetine was effective at relieving subjective handicaps caused by dizziness, specifically, in patients with high Self-Rating Depression Scale scores.

Effect of intramammary injection of rboGM-CSF on milk levels of chemiluminescence activity, somatic cell count, and Staphylococcus aureus count in Holstein cows with S. aureus subclinical mastitis.

The effect of intramammary injection of recombinant bovine granulocyte-macrophage colony-stimulating factor (rboGM-CSF, 400 microg/10 mL) on quarter milk levels of chemiluminescence (CL) activity, and somatic cell count (SCC) and shedding pattern of Staphylococcus aureus was investigated. Ten Holstein cows, naturally infected with S. aureus were used, with either early-stage or late-stage subclinical mastitis. Injection of rboGM-CSF caused a remarkable increase in milk CL activity with a peak at 6 h after the cytokine injection in the early- and late-stage groups. In the early-stage group, milk SCC stayed around preinjection level at 6 h, rose significantly on days 1 and 2, and was followed by a smooth and significant decline to an under preinjection level (below 200 000 cells/mL) on day 7 postinjection. Alternatively, in the late-stage group, milk SCC rose significantly at 6 h after the cytokine injection and maintained high levels thereafter. The milk S. aureus count decreased drastically by the cytokine injection in the early-stage group. The bacterial count was moderately decreased in the late-stage group, but increased back to preinoculation levels on day 7 after the cytokine injection. The results suggest that the rboGM-CSF has a potential as a therapeutic agent for S. aureus infection causing subclinical mastitis of dairy cows, if the cytokine is applied at the initial stage of infection.

[A clinical study of 104 patients with tongue cancer and the relationship between DNA ploidy and prognosis in 41 cases].

One-hundred and four patients with previously untreated tongue cancer seen in our department between 1986 and 1998 were enrolled in a clinical study. The DNA ploidy patterns observed in fresh frozen specimens obtained from 41 patients were analyzed, and prognostic factors were investigated. According to the TNM classification (UICC 1997), 43 patients had stage I tumors, 29 had stage II tumors, 17 had stage III tumors, and 15 had stage IV tumors. The 5-year cause-specific survival rates for each stage were 94.7%, 64.4%, 50.0% and 45.7%, respectively. The most frequent cause of death associated with the original disease was the recurrence of the disease in cervical lymph nodes (19/27, 70.4%). The occurrence of late cervical metastasis was high among patients with a T2N0 disease. Patients with stage II disease should undergo elective neck dissection or be carefully monitored using ultrasonography. Among the 41 cases in which the DNA ploidy pattern was analyzed, diploid patterns were found in 30 cases and aneuploid patterns were found in 11. The 5-year cause-specific survival rate and the 5-year locoregional control rate were significantly lower for the aneuploid cases (18.2%, 38.9%) than for the diploid cases (66.5%, 69.8%) (p = 0.0003, p = 0.0339). The incidence of distant metastasis was significantly higher among the aneuploid cases (6/11, 54.5%) than among the diploid cases (3/30, 10.0%) (p = 0.0058). The ploidy pattern, as determined by flow cytometric DNA analysis, may reflect the malignancy grade of tongue cancers.

Upregulation of Ca(v)3.2 T-type calcium channels targeted by endogenous hydrogen sulfide contributes to maintenance of neuropathic pain.

Hydrogen sulfide (H(2)S) formed from l-cysteine by multiple enzymes including cystathionine-gamma-lyase (CSE) is now considered a gasotransmitter in the mammalian body. Our previous studies have shown that H(2)S activates/sensitizes Ca(v)3.2 T-type Ca(2+) channels, leading to facilitation of somatic and visceral nociception, and that CSE-derived endogenous H(2)S participates in inflammatory pain. Here, we show novel evidence for involvement of the endogenous H(2)S-Ca(v)3.2 pathway in neuropathic pain. In the rat subjected to the right L5 spinal nerve cutting (L5SNC), a neuropathic pain model, i.p. administration of dl-propargylglycine (PPG) and beta-cyanoalanine, irreversible and reversible CSE inhibitors, respectively, strongly suppressed the neuropathic hyperalgesia/allodynia. The anti-hyperalgesic effect of PPG was reversed by intraplantar administration of NaHS, a donor for H(2)S, in the L5SNC rat. Intraplantar administration or topical application of mibefradil, a T-type Ca(2+) channel blocker, reversed hyperalgesia in the L5SNC rat. The protein levels of Ca(v)3.2, but not CSE, in the ipsilateral L4, L5 and L6 dorsal root ganglia were dramatically upregulated in the L5SNC rat. Finally, silencing of Ca(v)3.2 in DRG by repeated intrathecal administration of Ca(v)3.2-targeting siRNA significantly attenuated the neuropathic hyperalgesia in the L5SNC rat. In conclusion, our data suggest that Ca(v)3.2 T-type Ca(2+) channels in sensory neurons are upregulated and activated/sensitized by CSE-derived endogenous H(2)S after spinal nerve injury, contributing to the maintenance of neuropathic pain. We thus propose that Ca(v)3.2 and CSE could be targets for the development of therapeutic drugs for the treatment of neuropathic pain.

Horizontal canal type BPPV: bilaterally affected case treated with canal plugging and Lempert's maneuver.

A 54-year-old woman complained of positional vertigo. During 3 months' observation, the patient showed mostly geotropic or apogeotropic nystagmus due to right canalolithiasis or cupulolithiasis, however, she sometimes showed nystagmus which suggested left horizontal canalolithiasis. We suspected that she suffered from bilateral horizontal canal type benign paroxysmal positional vertigo (BPPV) and performed Lempert's maneuver for both directions, however, they were ineffective. She underwent canal plugging for right horizontal canal. After surgery she showed no positional nystagmus of right horizontal canal origin. However, apogeotropic nystagmus of the left horizontal canal origin was still observed. This nystagmus changed to geotropic nystagmus and finally disappeared following Lempert's maneuver for the left side. Bilateral horizontal canal BPPV is difficult to be resolved, probably because physical treatment for one side would move debris to the cupula in the other canal. Canal plugging combined with Lempert's maneuver to the other side is one treatment option for intractable bilateral horizontal canal BPPV.

Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation.

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA(A) receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel alpha2/delta subunit 1, calcineurin subunit Abeta and Ca(2+) pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.