Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2.
Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2.
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DOI：
10.1101/gad.308270.117
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发表时间：
2018-03-01
影响因子：
10.5
通讯作者：
Jan YN
中科院分区：
文献类型：
--
作者：
DeVault L;Li T;Izabel S;Thompson-Peer KL;Jan LY;Jan YN
DeVault等人表明，成年神经元具有再生能力，但随着动物年龄的增长而减弱。再生的树突表现出优先排列与细胞外基质，和抑制基质金属蛋白酶2导致增加树突再生。树突具有独特的结构和功能特性，使神经元能够从环境以及其他神经元接收信息。尽管它们在神经元功能中起着关键作用，但目前对神经元再生树突的能力缺乏了解。本研究描述了成年动物体内树突再生的结构和功能能力，并研究了神经元成熟对树突再生的影响。我们专注于第四类树突状树枝化（c4da）神经元的果蝇感觉系统，它有一个树突状乔木，经历了戏剧性的重塑在第一个3天的成年生活，然后保持一个相对稳定的形态之后。使用激光切断范例，我们监测再生后，急性和空间限制性损伤。我们发现，再生能力存在于成年神经元中，但随着动物年龄的增长而减弱。再生的树突恢复了接受功能。此外，我们发现再生的树突与细胞外基质（ECM）优先排列。最后，通过抑制基质金属蛋白酶2（Mmp2）来抑制ECM降解，以保持年轻成人的细胞外环境特征，从而增加树突再生。这些结果表明，树突在整个成年期保持再生潜力，再生能力随着年龄的增长而下降。
DeVault et al. show that the capacity for regeneration was present in adult neurons but diminished as the animal aged. The regenerated dendrites showed preferential alignment with the extracellular matrix, and inhibition of matrix metalloproteinase 2 led to increased dendrite regeneration. Dendrites possess distinct structural and functional properties that enable neurons to receive information from the environment as well as other neurons. Despite their key role in neuronal function, current understanding of the ability of neurons to regenerate dendrites is lacking. This study characterizes the structural and functional capacity for dendrite regeneration in vivo in adult animals and examines the effect of neuronal maturation on dendrite regeneration. We focused on the class IV dendritic arborization (c4da) neuron of the Drosophila sensory system, which has a dendritic arbor that undergoes dramatic remodeling during the first 3 d of adult life and then maintains a relatively stable morphology thereafter. Using a laser severing paradigm, we monitored regeneration after acute and spatially restricted injury. We found that the capacity for regeneration was present in adult neurons but diminished as the animal aged. Regenerated dendrites recovered receptive function. Furthermore, we found that the regenerated dendrites show preferential alignment with the extracellular matrix (ECM). Finally, inhibition of ECM degradation by inhibition of matrix metalloproteinase 2 (Mmp2) to preserve the extracellular environment characteristics of young adults led to increased dendrite regeneration. These results demonstrate that dendrites retain regenerative potential throughout adulthood and that regenerative capacity decreases with aging.
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