Sajjan S, Holsinger R M D, Fok S, Ebrahimkhani S, Rollo J L, Banati R B, Graeber M B
Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia.
Brain Tumor Research and Molecular Neuroscience & Neuropathology Laboratories, Brain and Mind Research Institute, Faculty of Medicine and Faculty of Health Sciences, The University of Sydney, Camperdown, NSW, Australia; Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
Neuroscience. 2014 Aug 22;274:331-40. doi: 10.1016/j.neuroscience.2014.05.052. Epub 2014 Jun 4.
Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic "synaptic stripping" was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions.
啮齿动物面神经切断术是一种公认的突触可塑性模型。创伤后“突触剥离”最初就是在这个系统中发现的。我们报告了小鼠和大鼠面神经核再生运动神经元中基质金属蛋白酶MMP12的上调。基质金属蛋白酶（matrix metallopeptidases，MMPs）是一类锌结合蛋白酶，能够降解细胞外基质成分并调节包括突触内信号网络在内的细胞外信号网络。轴突切断术后，面神经运动神经元中的MMP12蛋白表达增强，并在术后第3天达到峰值。神经元MMP12表达的峰值先于实验诱导的突触可塑性的峰值出现。与此同时，MMP12在细胞内重新分布，主要定位于神经元体细胞质膜下方。这两个发现都表明MMP12在突触剥离过程的神经元起始中发挥作用。MMP12是具有这种触发功能的首个候选分子，具有作为治疗靶点的潜力。此外，由于他汀类药物已被证明可增加MMP12的表达，干扰突触稳定性可能是这些广泛使用的药物对高级中枢神经系统功能产生副作用的一种机制。
