MMP-2 is involved in synaptic remodeling after cochlear lesion

Abstract

Lesion-induced neuroplasticity, including fiber degeneration, axonal growth, and synaptogenesis, involves dynamical changes of the extracellular matrix. We discovered that the matrix metalloprotease-2 (MMP-2), a major actor in extracellular matrix recomposition, is changed in distribution and increased in amount in the ventral cochlear nucleus after unilateral cochlear ablation. There was a remarkable coincidence of MMP-2 accumulation and GAP-43 expression in time and space. We obtained evidence indicating that MMP-2 is delivered to regions of emerging GAP-43 positive synaptic endings by postsynaptic neurons as well as by adjoining astrocytes. These results indicate a major role of MMP-2 in lesion-induced remodeling of central auditory networks and suggest a cooperativity with GAP-43-directed axonal outgrowth and synaptogenesis.