中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 390-391.doi: 10.4103/1673-5374.179035

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

长度为76nt的RNA被轴突转运到再生轴突和生长锥:它们会做什么?

  

  • 收稿日期:2015-12-03 出版日期:2016-03-15 发布日期:2016-03-15

76nt RNAs are transported axonally into regenerating axons and growth cones. What are they doing there?

Nicholas A. Ingoglia, Binta Jalloh   

  1. Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers University, Newark, NJ, USA (retired) (Ingoglia NA)
    Department of Cell Biology, Emory University, Atlanta, GA, USA(Jalloh B)
  • Received:2015-12-03 Online:2016-03-15 Published:2016-03-15
  • Contact: Nicholas A. Ingoglia, ingoglia67@gmail.com.

摘要:

成功的神经再生不仅需要神经元重建远端损伤部位的新轴突,而且这些新生长的轴突必须通过神经纤维导航以与靶细胞形成适当的突触连接。虽然成千上万的轴突可能占据再生神经或中枢神经系统束会是一幅壮观的景象,然而发育中的数十亿大脑神经元却一定要做到达成连接的类似任务。神经元要如何做到这一点?研究人员研究这些问题的方法之一是在胚胎发育或神经再生过程中在麻醉的实验动物神经元细胞体中引入放射性标记氨基酸。这种体内方法可以在神经元中标记新合成的蛋白质,其中的一些被运入伸长轴突。另一种已被用于研究的类似方法是轴突运输RNA,可以取代氨基酸的放射性标记RNA前体。这些实验的最初目标是探索合成蛋白质在轴突局部发生的可能性,如果蛋白质在轴突内被合成,那么主要稳定的RNA(核糖体和转移RNA)就能够在神经元细胞中被输送到轴突。这些研究带来了令人惊奇的发现,脊椎动物神经元中只有一类单一RNA,4S RNA(即共迁移上SDS PAGE与76nt,tRNA标记物),可以证明能够进行轴突运输,并仅在轴突生长(在金鱼的再生视神经轴突和大鼠坐骨神经)以及发育大鼠和小鸡大脑视神经轴突的伸长中进行。因此,76nt长度的RNA的轴突运输与GAP-43平行。

Abstract:

Successful nerve regeneration requires not only that neurons reconstruct new axons distal to the site of injury, but also that those growing axons must navigate through the neuropil to make appropriate synaptic connections with target cells. While this is an imposing task for the thousands of axons that may occupy a regenerating nerve or central nervous system tract, the billions of neurons in the developing brain must accomplish similar tasks making connections that number in the trillions. How do neurons do this? One of the ways researchers have studied these questions is to introduce radiolabeled amino acids into cell bodies of neurons in anaesthetized, experimental animals during embryonic development or nerve regeneration. This in vivo approach labels newly synthesized proteins in the neuron, some of which are transported into the elongating axon. A similar approach has been used to investigate the possibility that RNA is transported axonally, substituting radiolabeled RNA precursors for amino acids. The original goal of these experiments was to explore the possibility that protein synthesis could occur locally in axons, the logic being that if proteins were being synthesized in axons, then the major stable RNAs (ribosomal and transfer RNAs) should be produced in the neuronal cell body and transported into the axon. These studies resulted in the surprising finding that in vertebrate neurons only a single species of RNA, 4S RNA (that co-migrated on SDS PAGE with 76nt, tRNA markers), could be demonstrated to be transported axonally, and only during axon growth (in regenerating optic axons of goldfish and sciatic nerves of rats), and during elongation of optic axons in developing rat and chick brains. Thus, the axonal transport of 76nt RNAs, parallels that of GAP-43.