Shinder Michael E, Ramanathan Murugappan, Kaufman Galen D
Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77555-1063, USA.
J Vestib Res. 2006;16(4-5):147-69.
Commercial microarrays were used to identify transcriptome expression within vestibular related brain regions (vestibular brainstem and cerebellum, and caudotemporal cortical regions) during the acute period of recovery following unilateral surgical vestibular labyrinth ablation in the gerbil. As a representative model of vestibular compensation, vestibular lesions in the gerbil produced activation in a common set of genes related to vestibular compensation. The total RNA was prepared and amplified using Affymetrix Gene Chip probes from the Rat U34 Neurobiology and R230, and Mouse M430 gene sets, resulting in GCRMA summarized data from S+AA software. Matched rat and mouse genes from gerbil hybridization produced good interspecies synteny. Multiple gene target trends supported global increases in neuron excitability throughout the vestibular brainstem and cerebellum. We focused further on gene expression with anatomically asymmetric activation relative to the lesion, indicative of involvement in rebalancing central vestibular tone during the vestibular compensation process. Cluster analysis revealed distinct spatial (regional and ipsi-contra) and temporal patterns. The asymmetric genes were part of well-defined neuron-related networks and included multiple members of the glutamate and GABA neurotransmitter systems. Transcripts for D3 dopamine, glycine, and some GABA receptor signals increased quickly in the ipsilesional vestibular complex and then increased gradually in the contralateral region, restoring the expression symmetry. Alternatively, the NMDA binding subunit decreased gradually over the acute compensation period in the contralateral vestibular complex. There was evidence for numerous associations between signaling systems with PKC as one possible mediator between early changes in GABA and progressive changes in NMDA signaling. These data begin to define the compensatory response at the level of molecular cascades.
在沙鼠单侧手术性前庭迷路切除术后的急性恢复期，使用商业微阵列来鉴定前庭相关脑区（前庭脑干、小脑以及颞叶尾侧皮质区域）内的转录组表达。作为前庭代偿的代表性模型，沙鼠的前庭损伤激活了一组与前庭代偿相关的常见基因。使用来自大鼠U34神经生物学和R230以及小鼠M430基因集的Affymetrix基因芯片探针制备并扩增总RNA，从而得到来自S + AA软件的GCRMA汇总数据。沙鼠杂交产生的匹配大鼠和小鼠基因具有良好的种间同线性。多个基因靶点趋势支持前庭脑干和小脑整体神经元兴奋性的增加。我们进一步关注相对于损伤具有解剖学不对称激活的基因表达，这表明其参与了前庭代偿过程中中枢前庭张力的重新平衡。聚类分析揭示了不同的空间（区域和同侧 - 对侧）和时间模式。不对称基因是明确的神经元相关网络的一部分，包括谷氨酸和GABA神经递质系统的多个成员。D3多巴胺、甘氨酸和一些GABA受体信号的转录本在同侧前庭复合体中迅速增加，然后在对侧区域逐渐增加，恢复表达对称性。另外，NMDA结合亚基在对侧前庭复合体的急性代偿期逐渐减少。有证据表明信号系统之间存在众多关联，PKC可能是GABA早期变化与NMDA信号渐进变化之间的一种可能介质。这些数据开始在分子级联水平上定义代偿反应。
