Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation
Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation
复制标题
DOI：
10.1111/j.1471-4159.2006.03701.x
复制
发表时间：
2006-04-01
影响因子：
4.7
通讯作者：
Ethell, IM
中科院分区：
文献类型：
--
作者：
Bilousova, TV;Rusakov, DA;Ethell, IM
树突棘是树突轴的突起，树突轴是大脑中大多数兴奋性突触的所在地。尽管树突棘首先在神经元成熟期间出现，但树突棘在成年后仍保持可塑性，并且控制树突棘形态的分子机制的最新进展表明它们对微环境的变化极其敏感。影响脊柱形态的众多因素包括细胞外基质 (ECM) 的成分和调节因子。 ECM 的修改对于修复整个身体（包括中枢神经系统）的损伤至关重要。基质金属蛋白酶 (MMP)-7/基质溶素是病原体感染期间、神经挤压后和脑炎性疾病期间 ECM 的关键调节因子。我们研究了 MMP-7 对海马神经元培养物中树突棘的影响，发现它诱导成熟的短蘑菇状树突棘转化为长而细的丝状伪足，让人想起未成熟的树突棘。这些变化伴随着 F-肌动蛋白从脊柱头到树突轴中厚实的绳状结构的戏剧性重新分布。引人注目的是，MMP-7 对树突棘的作用与 NMDA 治疗的作用相似，并且两者都可以被通道特异性拮抗剂阻断。这些发现首次直接证明 MMP 可以影响成熟树突棘的形态，从而影响突触稳定性。
Dendritic spines are protrusions from the dendritic shaft that host most excitatory synapses in the brain. Although they first emerge during neuronal maturation, dendritic spines remain plastic through adulthood, and recent advances in the molecular mechanisms governing spine morphology have shown them to be exquisitely sensitive to changes in the micro-environment. Among the many factors affecting spine morphology are components and regulators of the extracellular matrix (ECM). Modification of the ECM is critical to the repair of injuries throughout the body, including the CNS. Matrix metalloproteinase (MMP)-7/matrilysin is a key regulator of the ECM during pathogen infection, after nerve crush and in encephalitogenic disorders. We have investigated the effects of MMP-7 on dendritic spines in hippocampal neuron cultures and found that it induces the transformation of mature, short mushroom-shaped spines into long, thin filopodia reminiscent of immature spines. These changes were accompanied by a dramatic redistribution of F-actin from spine heads into thick, rope-like structures in the dendritic shaft. Strikingly, MMP-7 effects on dendritic spines were similar to those of NMDA treatment, and both could be blocked by channel-specific antagonists. These findings are the first direct evidence that MMPs can influence the morphology of mature dendritic spines, and hence synaptic stability.