Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3-deficient mice
Altered neuronal architecture and plasticity in the visual cortex of adult MMP-3-deficient mice
复制标题
DOI：
10.1007/s00429-014-0819-4
复制
发表时间：
2015-09-01
影响因子：
3.1
通讯作者：
Arckens, Lutgarde
中科院分区：
文献类型：
--
作者：
Aerts, Jeroen;Nys, Julie;Arckens, Lutgarde
基质金属蛋白酶（MMPs）是一种锌离子依赖性内肽酶，通过调节细胞外基质蛋白、受体、粘附分子、生长因子和细胞骨架蛋白，对正常脑发育和神经可塑性起重要作用。具体地说，MMP-3最近被牵连在突触可塑性，视丘依赖性学习和神经元的发育和迁移在小脑。然而，这种酶在新皮质中的功能尚未得到充分研究。因此，我们探讨了成年MMP-3缺陷（MMP-3（-/-））小鼠视皮层神经元结构的表型特征和经验依赖性皮层可塑性的能力。Golgi-Cox染色显示，与野生型（WT）动物相比，成年MMP-3（-/-）小鼠视皮层中第V层锥体神经元的顶端树突长度显著减少，顶端树突数量增加。此外，在MMP-3（-/-）小鼠的视皮层中检测到磷酸化和非磷酸化神经丝蛋白（NF）-高、磷酸化NF-中、NF-低和α-内连接蛋白的显著上调。为了评估MMP-3缺乏对皮质可塑性的影响，我们单眼摘除成年MMP-3（-/-）小鼠，并分析摘除后7周对侧视觉皮质的再激活。与先前在C57 Bl/6 J成年小鼠中的结果相反，活动仍然局限于双眼区，并且没有扩展到指示异常睁眼增强的单眼区域。V1外侧和内侧单眼皮质的永久性活动减退也表明缺乏跨模态可塑性。这些观察结果表明，MMP-3的遗传失活对成年小鼠视皮层的结构完整性和可塑性反应具有深远的影响。
Matrix metalloproteinases (MMPs) are Zn2+-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 alpha-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.