Paterson Janet M, Short Duncan, Flatman Peter W, Seckl Jonathan R, Aitken Alastair, Dutia Mayank B
Centre for Integrative Physiology, Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
J Physiol. 2006 Sep 15;575(Pt 3):777-88. doi: 10.1113/jphysiol.2006.112409. Epub 2006 Jul 6.
The molecular mechanisms of neural and synaptic plasticity in the vestibular nuclei during 'vestibular compensation', the behavioural recovery that follows deafferentation of one inner ear, are largely unknown. In this study we have used differential proteomics techniques to determine changes in protein expression in ipsi-lesional and contra-lesional medial vestibular nuclei (MVN) of rats, 1 week after either sham surgery or unilateral labyrinthectomy (UL). A systematic comparison of 634 protein spots in two-dimensional electrophoresis gels across five experimental conditions revealed 54 spots, containing 26 proteins whose level was significantly altered 1 week post-UL. The axon-guidance-associated proteins neuropilin-2 and dehydropyriminidase-related protein-2 were upregulated in the MVN after UL. Changes in levels of further specific proteins indicate a coordinated upregulation of mitochondrial function, ATP biosynthesis and phosphate metabolism in the vestibular nuclei 1 week post-UL. These may reflect the metabolic energy demands of processes such as gliosis, neuronal outgrowth and synaptic remodelling that occur after UL. Our findings suggest novel roles for axon elaboration and guidance molecules, as well as mitochondrial and metabolic regulatory proteins, in the post-lesional physiology of the MVN during vestibular system plasticity.
在“前庭代偿”过程中,即一侧内耳传入神经切断后出现的行为恢复过程中,前庭核内神经和突触可塑性的分子机制在很大程度上尚不清楚。在本研究中,我们使用差异蛋白质组学技术,来确定假手术或单侧迷路切除术(UL)1周后,大鼠患侧和健侧内侧前庭核(MVN)中蛋白质表达的变化。对五个实验条件下二维电泳凝胶中的634个蛋白质点进行系统比较,发现了54个点,包含26种蛋白质,其水平在UL后1周有显著变化。轴突导向相关蛋白神经纤毛蛋白-2和脱氢嘧啶酶相关蛋白-2在UL后的MVN中上调。其他特定蛋白质水平的变化表明,UL后1周前庭核中线粒体功能、ATP生物合成和磷酸盐代谢协同上调。这些可能反映了UL后发生的如神经胶质增生、神经元生长和突触重塑等过程对代谢能量的需求。我们的研究结果表明,轴突形成和导向分子以及线粒体和代谢调节蛋白在前庭系统可塑性过程中MVN损伤后的生理学中具有新的作用。