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

Abstract

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 and in 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.

Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When Compared with Other Brainstem Motor Systems

“…The presence of BDNF protein and the expression of the mRNA have been demonstrated in adult rat vestibular and prepositus neurons (Li et al, 2001). Since vestibular cells also project toward facial motoneurons (Shaw and Baker, 1983), they could also serve as an anterograde source of neurotrophins for these cells.…”

BDNF signaling in the rat cerebello‐vestibular pathway during vestibular compensation: BDNF signaling in vestibular compensation

“…Our results are also consistent with Li et al . , who found an increase in the BDNF mRNA level in the ipsi‐lesional MVN at 6 h after UL by performing quantitative real‐time PCR (qPCR) in rats. However, using immunohistochemistry, Smith et al .…”

“…However, Li et al . found asymmetric expression of BDNF mRNA in the MVN of rats after UL . Hence, it remains unclear how components of the BDNF signaling pathway are expressed in the cerebello‐vestibular pathway during vestibular compensation.…”

Plastic events in the vestibular nuclei during vestibular compensation: The brain orchestration of a "deafferentation" code

“…1D) BDNF up-regulation is found bilaterally in the lateral VN in the UL guinea pig (Smith et al, 1998), and blockade of BDNF expression in this nucleus delays postural compensation (Bolger et al, 1999). Moreover, BDNF contribution to vestibular compensation has been confirmed by in situ hybridization data: an increased expression of the mRNA coding for BDNF has been shown in the ipsilateral medial VN and in the contralateral inferior olive in the UL rat (Li et al, 2001). We have investigated BDNF, NGF, and NT-3 expression in our UVN cat model, and confirmed the bilateral up-regulation of BDNF along with its TrKB receptor, both of which appeared as early as 1 day after UVN and peaked at 3 days postlesion in the inferior and lateral VN and the inferior olive.…”