Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3-deficient mice

Abstract

Matrix metalloproteinases (MMPs) are Zn(2+)-dependent endopeptidases considered to be essential for normal brain development and neuroplasticity by modulating extracellular matrix proteins, receptors, adhesion molecules, growth factors and cytoskeletal proteins. Specifically, MMP-3 has recently been implicated in synaptic plasticity, hippocampus-dependent learning and neuronal development and migration in the cerebellum. However, the function(s) of this enzyme in the neocortex is understudied. Therefore, we explored the phenotypical characteristics of the neuronal architecture and the capacity for experience-dependent cortical plasticity in the visual cortex of adult MMP-3-deficient (MMP-3(-/-)) mice. Golgi-Cox stainings revealed a significant reduction in apical dendritic length and an increased number of apical obliques for layer V pyramidal neurons in the visual cortex of adult MMP-3(-/-) mice compared to wild-type (WT) animals. In addition, a significant upregulation of both phosphorylated and non-phosphorylated neurofilament protein (NF)-high, phosphorylated NF-medium, NF-low and α-internexin was detected in the visual cortex of MMP-3(-/-) mice. To assess the effect of MMP-3 deficiency on cortical plasticity, we monocularly enucleated adult MMP-3(-/-) mice and analyzed the reactivation of the contralateral visual cortex 7 weeks post-enucleation. In contrast to previous results in C57Bl/6J adult mice, activity remained confined to the binocular zone and did not expand into the monocular regions indicative for an aberrant open-eye potentiation. Permanent hypoactivity in the monocular cortex lateral and medial to V1 also indicated a lack of cross-modal plasticity. These observations demonstrate that genetic inactivation of MMP-3 has profound effects on the structural integrity and plasticity response of the visual cortex of adult mice.

A Tool for Brain-Wide Quantitative Analysis of Molecular Data upon Projection into a Planar View of Choice

“…We performed in situ hybridization for zif268 as described before (van Brussel et al, 2009; Van Brussel et al, 2011; Nys et al, 2014; Aerts et al, 2014b; Smolders et al, 2015). A series of coronal sections between Bregma levels −2.0 and −4.4 mm were selected to span the striate and extrastriate areas.…”

A proteomic approach to understand MMP‐3‐driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors

“…This observation perfectly fits our previous findings on Purkinje cell morphology in MMP‐3 −/− mice, where we also noticed a reduced dendritic tree size, but no changes in soma size, in postnatal and adult MMP‐3 −/− cerebella (Van Hove et al, ). Of note, also a clear reduction in apical dendritic length of pyramidal neurons has recently been demonstrated in the visual cortex of adult MMP‐3 −/− mice (Aerts et al, ).…”

Matrix metalloproteinase-3 in brain physiology and neurodegeneration

“…The Golgi-stained MMP-3 -/pyramidal cells from layer V of the visual cortex exhibit significantly shorter apical dendrites compared to the wild-type controls. 35 On the contrary, Nowak et al have shown that there are no significant differences between morphology of MMP-3 -/pyramidal neurons in the CA1 hippocampal field in comparison to the wild-type group. 36 Collectively, these studies suggest that the functioning of the MMP-3 in developing CNS is more complex and may depend on the region of the brain.…”