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

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• 作者：Chisako Masumura ; Arata Horii ; Kenji Mitani ; Tadashi Kitahara ; Atsuhiko Uno ; Takeshi Kubo
• 关键词：Vestibular compensation ; Calcium channel ; Calcineurin ; Plasma membrane Ca²⁺ ATPase (PMCA)
• 刊名：Brain Research
• 出版年：2007
• 出版时间：23 March 2007
• 年：2007
• 卷：1138
• 期：Complete
• 页码：129-135
• 全文大小：381 K

文摘

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, our previous 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. 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.