Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

Michaela Fredrich,Robert-Benjamin Illing

doi:10.1155/2011/859359

Michaela Fredrich, Robert-Benjamin Illing

Open Access

https://doi.org/10.1155/2011/859359

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Journal: Neural Plasticity	Publication Date: Jan 1, 2011
Citations: 4	License type: CC BY 3.0

Affiliation: University of Freiburg

Abstract

The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM), were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN) following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB) prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43) into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

Highlights

Cochlear ablation entails Wallerian degeneration of the auditory nerve fibers and loss of their synaptic terminals in the cochlear nucleus (CN) [1]
These fibers originate from neurons of the medial olivocochlear (MOC) system arising in the ventral nucleus of the trapezoid body (VNTB), a rhombencephalic region characterized by conspicuously large cholinergic neurons [10, 12]
Whereas these effects were strong by POD1 and POD3 (Figures 1(b) and 1(c)), the pattern of Matrix metalloproteinases (MMPs)-9 staining almost returned to the preoperative condition by POD7 (Figure 1(d))

Summary

Introduction

Cochlear ablation entails Wallerian degeneration of the auditory nerve fibers and loss of their synaptic terminals in the cochlear nucleus (CN) [1]. GAP-43 reemerges in fibers and presynaptic terminals growing into the anteroventral CN (AVCN) [10, 11] These fibers originate from neurons of the medial olivocochlear (MOC) system arising in the ventral nucleus of the trapezoid body (VNTB), a rhombencephalic region characterized by conspicuously large cholinergic neurons [10, 12]. On their way to the inner ear, MOC neurons give off axon collaterals into the cochlear nucleus [13,14,15], terminating in the marginally located granule cell layer of AVCN in normal animals [16, 17]. In the present study GAP-43 was used as a marker for axonal growth and reactive synaptogenesis

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