Sensory deafferentation modulates and redistributes neurocan in the rat auditory brainstem.

ABSTRACT: INTRODUCTION:Cochlear ablation causing sensory deafferentation (SD) of the cochlear nucleus triggers complex re-arrangements in the cellular and molecular communication networks of the adult mammalian central auditory system. Participation of the extracellular matrix (ECM) in these processes is not well understood. METHODS:We investigated consequences of unilateral SD for the expression and distribution of the chondroitin sulfate proteoglycans, neurocan (Ncan) and aggrecan (Agg), alongside various plasticity markers in the auditory brainstem of the adult rat using immunohistochemical techniques. RESULTS:In the deafferented ventral cochlear nucleus (VCN), Ncan expression increased massively within 3 postoperative days (POD), but rapidly decreased thereafter. Agg showed a similar but less pronounced progression. Decrease in Ncan was spatially and temporally related to the re-innervation of VCN documented by the emergence of growth-associated protein Gap43 contained in nerve fibers and presynaptic boutons. Concurrently, astrocytes grew and expressed matrix metalloproteinase-2 (MMP2), an enzyme known to emerge only under re-innervation of VCN. MMP2 is capable of cleaving both Ncan and Agg when released. A transient modulation of the ECM in the central inferior colliculus on the side opposite to SD occurred by POD1. Modulations of glutamatergic synapses and Gap43 expression were detected, reflecting state changes of the surrounding tissue induced by transsynaptic effects of SD. CONCLUSIONS:The ECM variously participates in adaptive responses to sudden deafness by SD on several levels along the central auditory pathway, with a striking spatial and temporal relationship of Ncan modulation to astrocytic activation and to synaptogenesis.

SUBMITTER: Heusinger J 

PROVIDER: S-EPMC6710208 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature