Travo Cécile, Gaboyard-Niay Sophie, Chabbert Christian
INSERM U1051, Institute for Neurosciences Montpellier, France.
Front Neurol. 2012 Jun 6;3:91. doi: 10.3389/fneur.2012.00091. eCollection 2012.
In a previous study, we observed spontaneous restoration of vestibular function in young adult rodents following excitotoxic injury of the neuronal connections within vestibular endorgans. The functional restoration was supported by a repair of synaptic contacts between hair cells and primary vestibular neurons. This process was observed in 2/3 of the animals studied and occurred within 5 days following the synaptic damage. To assess whether repair capacity is a fundamental trait of vestibular endorgans and to decipher the cellular mechanisms supporting such a repair process, we studied the neuronal regeneration and synaptogenesis in co-cultures of vestibular epithelia and Scarpa's ganglion from young and adult rodents. We demonstrate that, under specific culture conditions, primary vestibular neurons from young mice or rats exhibit robust ability to regenerate nervous processes. When co-cultured with vestibular epithelia, primary vestibular neurons were able to establish de novo contacts with hair cells. Under the present paradigm, these contacts displayed morphological features of immature synaptic contacts. Preliminary observations using co-cultures of adult rodents suggest that this reparative capacity remained in older mice although to a lesser extent. Identifying the basic mechanisms underlying the repair process may provide a basis for novel therapeutic strategies to restore mature and functional vestibular synaptic contacts following damage or loss.
在先前的一项研究中,我们观察到年轻成年啮齿动物在前庭终器内神经元连接发生兴奋性毒性损伤后,前庭功能会自发恢复。这种功能恢复得到了毛细胞与前庭初级神经元之间突触联系修复的支持。在三分之二的研究动物中观察到了这一过程,且发生在突触损伤后的5天内。为了评估修复能力是否是前庭终器的一个基本特征,并解读支持这种修复过程的细胞机制,我们研究了来自年轻和成年啮齿动物的前庭上皮与斯卡帕神经节共培养物中的神经元再生和突触形成。我们证明,在特定培养条件下,来自年轻小鼠或大鼠的前庭初级神经元表现出强大的神经突起再生能力。当前庭初级神经元与前庭上皮共培养时,它们能够与毛细胞重新建立联系。在当前模式下,这些联系呈现出不成熟突触联系的形态特征。使用成年啮齿动物共培养物的初步观察表明,这种修复能力在老年小鼠中仍然存在,尽管程度较低。确定修复过程的基本机制可能为损伤或丧失后恢复成熟且功能性前庭突触联系的新型治疗策略提供基础。