Plasticity associated reorganization of the extracellular matrix in the rat's auditory brainstem after unilateral cochleotomy

Introduction:

Plasticity enables the central auditory system to adapt to changes in the sensory-evoked activity such as sudden deafness. We investigated how plastic processes induced in the adult auditory brainstem by unilateral cochleotomy correlate with changes of the extracellular matrix (ECM). We focused on the expression of the plasticity associated protein Gap43 and the lectican neurocan in the rat's cochlear nucleus (AVCN) and inferior colliculus (CIC).

Methods:

Adult Wistar rats were deafened by unilateral cochlear ablation. After surgery, animals survived for 1 (n = 5), 3 (n = 18), 7 (n = 6) or 14 (n = 3) days before their brains were removed for immunhistochemical staining. Age matched rats of the control group (n = 2) did not undergo cochlear ablation.

Results:

With an onset before postoperative day (POD) 3, Gap43 positive fibers appeared in the AVCN. We found a strong upregulation of neurocan locally corresponding to Gap43. While newly forming synapses organize around neurons, neurocan is removed from their surfaces by POD7. Simultaneously, astrocytic processes began expressing the matrix metalloproteinase MMP-2 known to cleave ECM. Former studies indicate that astrocytic expression of this enzyme only occurs if reinnervation of AVCN is not prevented. We also noted a transient, but significant rise of neurocan in the contralateral CIC by POD1.

Conclusion:

The auditory brainstem is a suitable model to study central nervous plasticity as it includes synaptogenesis. We found specific components of the ECM upregulated on the deafferented side. The enzymatic degradation of these molecules by MMP-2 seems essential for the reinnervation to succeed. We conclude that a dynamic regulation of the ECM is part of the lesion-induced reorganization of the central auditory system.

Publikationsverlauf

Publikationsdatum:
18. April 2018 (online)