The fusogen AFF-1 can rejuvenate the regenerative potential of adult dendritic trees by self-fusion
The fusogen AFF-1 can rejuvenate the regenerative potential of adult dendritic trees by self-fusion
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DOI：
10.1242/dev.150037
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发表时间：
2017-07-01
期刊：
影响因子：
4.6
通讯作者：
Podbilewicz, Benjamin
中科院分区：
文献类型：
--
作者：
Kravtsov, Veronika;Oren-Suissa, Meital;Podbilewicz, Benjamin
衰老的大脑经历影响大脑稳态、神经元功能和认知的结构变化。树突状乔木的复杂结构对理解脑损伤后的年龄依赖性形态学改变、行为可塑性和重塑提出了挑战。在这里，我们使用的PVD多模态神经元C。elegans作为研究衰老如何影响神经元可塑性的模型。利用共聚焦活体成像技术对C. elegans PVD神经元，我们证明了复杂的树突状乔木的年龄相关的渐进形态学改变。我们发现，daf-2基因的突变，它编码胰岛素样生长因子受体的直系同源物，不能抑制树突的进行性形态老化，也不能防止老化过程中对粗糙触摸的反应轻微下降。我们发现，PVD老化的特点是实验性激光树突切除术后树突再生潜力的大幅度下降。此外，AFF-1介导的自我融合的横切树突状树的重塑可以通过daf-2突变在老年动物中恢复，并且可以通过融合蛋白AFF-1的异位表达差异地重建。因此，异位表达的融合因子AFF-1的PVD和突变的daf-2差异再生的一些方面的树突状细胞损伤后再生。
The aging brain undergoes structural changes that affect brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors. We show that mutations in daf-2, which encodes an insulin-like growth factor receptor ortholog, fail to inhibit the progressive morphological aging of dendrites and do not prevent the minor decline in response to harsh touch during aging. We uncovered that PVD aging is characterized by a major decline in the regenerative potential of dendrites following experimental laser dendrotomy. Furthermore, the remodeling of transected dendritic trees by AFF-1-mediated self-fusion can be restored in old animals by daf-2 mutations, and can be differentially re-established by ectopic expression of the fusion protein AFF-1. Thus, ectopic expression of the fusogen AFF-1 in the PVD and mutations in daf-2 differentially rejuvenate some aspects of dendritic regeneration following injury.