Spatiotemporal Dynamics of Brain-Derived Neurotrophic Factor mRNA Induction in the Vestibulo-Olivary Network during Vestibular Compensation

摘要

Vestibular compensation, which is the behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL), is attributed to functional and structural reorganization of neural networks in the central vestibular system. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to this recovery process, we investigated changes in mRNA expression levels in the central vestibular system after UL. We evaluated BDNF mRNA expression levels by quantitative reverse transcription-PCR andin situ hybridization. We found that BDNF mRNA is differentially induced in the medial vestibular nucleus ipsilateral to UL and in the prepositus hypoglossi and inferior olive on the contralateral side. The BDNF mRNA induction lasted for at least 24 hr and returned to the basal expression level within 72 hr after UL. In contrast to BDNF mRNA induction, the expression of an immediate-early gene, c-fos, quickly reached the maximum level at 3 hr and decreased to the basal level within 24 hr after UL. Neither BDNF or c-fos induction was observed in sham-operated animals. The persistent induction of BDNF after UL temporally corresponded to early behavioral manifestations of vestibular compensation. We further found that trkB mRNA was expressed in the central vestibular network at high levels, although its expression levels did not change over time after UL. Because BDNF is implicated in regulating synaptic structure and function, these results provide support for the hypothesis that BDNF is involved in neuronal reorganization that allows vestibular compensation.