Article
Initiation of nervous reorganization following complete deafening by cochlear ablation depends on specific growth proteins in the cochlear nucleus of the adult rat
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Authors
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Michaela Fredrich
- Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, Freiburg, Germany
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Robert-Benjamin Illing
- Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, Freiburg, Germany
| Published: | August 3, 2011 |
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Outline
Text
Introduction: Unilateral removal of the spiral ganglion causes degeneration of the auditory nerve and leads to complete sensory deafferentation of the cochlear nucleus (CN). These degenerative processes are followed by a phase of CN re-innervation which can be recognized by the expression of the growth associated protein GAP-43 in numerous fibers and presynaptic terminals emerging in CN. The matrix metalloproteinases MMP-9 and MMP-2, modulators of the extracellular matrix, have key functions in degeneration as well as regeneration of nervous tissue.
Methods: We aimed to determine if the lesion-dependent emergence of GAP-43 positive axons and the dynamics of MMP-9 and MMP-2 in degeneration and re-innervation are functionally related. Prior to cochlear ablation, kainic acid (KA) was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB) of the auditory brainstem, killing the neurons that we knew deliver GAP-43 to CN as a consequence of its deafferentation.
Results: The response of MMP-9 to cochlear ablation was strongest one day after deafferentation (POD1). By contrast, MMP-2 distribution and amount were changed not before POD3 and developed further towards POD7. Suppressing re-innervation by a preceding injection of KA into VNTB, we found that redistribution of MMP-9 in CN in the early degenerative Phase was unaffected of the initiation of the re-innervative phase. However, changes in the distribution of MMP-2 normally seen after sensory deafferentation were reversed if GAP-43 positive axons were prevented from growing in CN.
Conclusions: Arrival of GAP-43 positive axons in CN is indicative for the initiation of re-innervation following sensory deafferentation. We found that a suppression of the growth of GAP-43 containing axons caused a return of changes in distribution and amount of MMP-2 to control levels, whereas MMP-9 remained unaffected by the failure of re-innervation. Knowledge of the causal dependencies in lesion-induced neuronal reorganization processes are essential to design therapies for future support of patients suffering from nerve cell loss in sense organs or brain.
