Molecular mechanisms of vestibular compensation and treatment strategy of vertigo

前庭补偿的神经化学机制的调查，损伤诱导的神经元可塑性的模型，揭示了电压门控钙通道（VGCC）和细胞内钙信号的参与。事实上，微阵列分析显示，在单侧前庭传入神经阻滞（UVD）后，同侧前庭核复合体（VNC）中的一些钙信号相关基因如L型钙通道α2亚基、钙调神经磷酸酶和质膜Ca 2 + ATP酶1（PMCA 1）表达上调。为了进一步阐明钙信号相关分子在前庭代偿中的作用，我们使用了定量实时聚合酶链反应（PCR）方法来确认微阵列结果，并研究了这些分子在不同代偿阶段（UVD后6小时至2周）的表达变化。我们还研究了Bechterew现象过程中基因表达的变化以及钙调神经磷酸酶抑制剂对前庭代偿的影响。 ...更多信息 Real-time PCR结果显示，UVD后6 h，同侧VNC中VGCC α2亚基、PMCA 2和钙调神经磷酸酶基因表达短暂上调。随后的UVD，诱导Bechterew现象，再现了在初始UVD中观察到的PMCA 2和钙调神经磷酸酶基因表达变化的完全镜像，而VGCC基因的α2亚基在第二次损伤同侧的VNC中有增加的趋势。预先给予钙调磷酸酶抑制剂FK 506，可使前庭代偿减慢，且呈剂量依赖性。虽然目前还不确定这些基因表达的变化是否与前庭代偿的分子机制有因果关系，但这一观察结果表明，在通过上调VGCC增加Ca 2+流入同侧VNC神经元后，钙调神经磷酸酶可能参与其突触可塑性。相反，PMCA 2（一种脑特异性钙泵）的上调将增加这些神经元的钙外流，并可能防止UVD后的细胞损伤。少

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