Campos-Torres A, Touret M, Vidal P P, Barnum S, de Waele C
Department of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB/842, Birmingham, AL 35294, USA.
Neuroscience. 2005;130(4):853-65. doi: 10.1016/j.neuroscience.2004.08.052.
In this study, we investigated whether changes in the vestibular neuronal activity per se influence the pattern of astrocytes morphology, glial fibrillary acidic protein (GFAP) expression and ultimately their activation within the vestibular nuclei after unilateral transtympanic tetrodotoxin (TTX) injections and after unilateral inner ear lesion. The rationale was that, theoretically the noninvasive pharmacological functional blockade of peripheral vestibular inputs with TTX, allowed us to dissociate the signals exclusively related to the shutdown of the resting activity of the first-order vestibular neurons and from neuronal signals associated with trans-ganglionic changes in first order vestibular neurons induced by unilateral labyrinthectomy (UL). Since the cochlea was removed during the surgical procedure, we also studied the astrocytic reaction within the deafferented cochlear nuclei. No significant changes in the distribution or relative levels of GFAP mRNA expression, relative levels of GFAP protein or immunoreactivity for GFAP were found in the ipsilateral vestibular nuclei at any post-TTX injection times studied. In addition, no sign of microglia activation was observed. In contrast, a robust increase of the distribution and relative levels of GFAP mRNA expression, protein levels and immunoreactivity was observed in the deafferented vestibular and cochlear nuclei beginning at 1 day after inner ear lesion. GFAP mRNA expression and immunoreactivity in the cochlear nucleus was qualitatively stronger than in the ipsilateral vestibular nuclei. The results suggest that astrocyte activation in the vestibular nuclei is not related to drastic changes of vestibular nuclei neuronal activity per se. Early trans-ganglionic changes due to vestibular nerve dendrites lesion provoked by the mechanical destruction of vestibular receptors, most probably induced the glial reaction. Its functional role in the vestibular compensation process remains to be elucidated.
在本研究中,我们调查了单侧经鼓膜注射河豚毒素(TTX)以及单侧内耳损伤后,前庭神经元活动本身的变化是否会影响星形胶质细胞形态模式、胶质纤维酸性蛋白(GFAP)表达,以及最终它们在前庭核内的激活情况。理论依据是,从理论上讲,用TTX对外周前庭输入进行无创药理学功能阻断,使我们能够将仅与一级前庭神经元静息活动停止相关的信号,与由单侧迷路切除术(UL)诱导的一级前庭神经元跨神经节变化相关的神经元信号区分开来。由于在手术过程中切除了耳蜗,我们还研究了去传入耳蜗核内的星形胶质细胞反应。在所研究的任何TTX注射后时间点,同侧前庭核内GFAP mRNA表达的分布或相对水平、GFAP蛋白的相对水平或GFAP免疫反应性均未发现显著变化。此外,未观察到小胶质细胞激活的迹象。相比之下,在内耳损伤后第1天开始,去传入前庭核和耳蜗核内GFAP mRNA表达的分布和相对水平、蛋白水平及免疫反应性均显著增加。耳蜗核内的GFAP mRNA表达和免疫反应性在质量上比同侧前庭核更强。结果表明,前庭核内星形胶质细胞的激活与前庭核神经元活动本身的剧烈变化无关。前庭感受器机械破坏引发的前庭神经树突损伤导致的早期跨神经节变化,很可能诱发了胶质细胞反应。其在前庭代偿过程中的功能作用仍有待阐明。