Molecular mechanisms of vestibular compensation and treatment strategy of vertigo
| Project/Area Number |
17591788
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Osaka University |
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Principal Investigator |
HORII Arata Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (30294060)
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| Co-Investigator(Kenkyū-buntansha) |
KITAHARA Tadashi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30343255)
三代 康雄 大阪大学, 医学系研究科, 講師 (00263260)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | vertigo / vestibular compensation / gene / molecular biology / labyrinthectomy / マイクロアレー / カルシニュリン / microarray / カルシウム |
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| Research Abstract |
Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca2+ channels (VGCC) and intracellular Ca2+ signaling. Indeed, microarray analysis showed an up-regulation of some calcium signaling-related genes such as the α2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca2+ 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.
… More
Real-time PCR showed that genes for the α2 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 α2 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 Ca2+ 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 Ca2+ pump, would increase an efflux of Ca2+ from those neurons and perhaps prevent cell damage following UVD. Less
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Factors relating to the vertigo control and hearing changes following intratympanic gentamicin for intractable Meniere's disease.2006
Author(s)
A.Horii, T.Saika, A.Uno, S.Nishiike, M.Nishimura, K.Mitani, T.Kitahara, M.Fukushima, A.Nakagawa, C.Masumura, T.Sasaki, K.Kizawa, T.Kuho
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Journal Title
Otology and Neurotology 27
Pages: 896-900
Related Report
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