中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (7): 1033-1042.doi: 10.4103/1673-5374.187019

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

修复创伤性神经元质膜损害

  

  • 出版日期:2016-07-30 发布日期:2016-07-30
  • 基金资助:

    美国NIH基金

Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells

George D. Bittner*, Christopher S. Spaeth§, Andrew D. Poon, Zachary S. Burgess, Christopher H. McGill   

  1. Department of Neuroscience, The University of Texas at Austin, Austin, TX, USA
  • Online:2016-07-30 Published:2016-07-30
  • Contact: George D. Bittner, Ph.D., bittner@austin.utexas.edu.
  • Supported by:

    This study was supported by grants from the Lone Star Paralysis Foundation to GDB and by an NIH grant R01 NS081063 to GDB.

摘要:

现密封修复包括由小孔来完成横断质膜伤害,是细胞存活的关键,尤其是对神经元再生很少胞体。我们首先描述和评价细胞密封的不同措施。如形态/超微结构观察,膜电位和输入电阻等指标对质膜密封的评估很模糊。与此相反,如果能适当地使用,离子电流的流动和染料的障碍的措施可以提供更准确的评估。我们描述各种物质(钙,钙蛋白酶,细胞骨架蛋白,ESCRT蛋白,mUNC-13,美国国家科学基金会,PEG)和生化途径(PKA,PKC,PLC EPAC,胞质氧化)对质膜密封概率的影响,并表明与质膜密封相关物质、通路及细胞事件都发生了很大的进展。密封期间,钙离子以连续方式动员囊泡和其它膜结构(溶酶体,线粒体等)流入,几秒到几分钟形成囊状栓塞并逐渐限制越来越小分子和离子的扩散。文章描述了轴突横切后核周体钙水平的增加如何导致神经元胞体胞体存活的降低。最后,Bittner教授推测质膜密封,沃勒变性,和聚乙二醇(PEG)的密封细胞膜对切断轴突的再生能力之间的关系应成为创伤的周围神经将来的治疗一个重要的考虑因素。更好的认识参与质膜密封细胞质的生化途径和结构可能为制定创伤性神经损伤、卒中、肌肉萎缩症、以及其他疾病的治疗提供的新的见解。

Abstract:

The repair (sealing) of plasmalemmal damage, consisting of small holes to complete transections, is critical for cell survival, especially for neurons that rarely regenerate cell bodies. We first describe and evaluate different measures of cell sealing. Some measures, including morphological/ultra-structural observations, membrane potential, and input resistance, provide very ambiguous assessments of plasmalemmal sealing. In contrast, measures of ionic current flow and dye barriers can, if appropriately used, provide more accurate assessments. We describe the effects of various substances (calcium, calpains, cytoskeletal proteins, ESCRT proteins, mUNC-13, NSF, PEG) and biochemical pathways (PKA, PKC, PLC, Epac, cytosolic oxidation) on plasmalemmal sealing probability, and suggest that substances, pathways, and cellular events associated with plasmalemmal sealing have undergone a very conservative evolution. During sealing, calcium ion influx mobilizes vesicles and other membranous structures (lysosomes, mitochondria, etc.) in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to minutes. Furthermore, we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets, or in a single step involving the fusion of one large wound vesicle with the nearby, undamaged plasmalemma. We describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the perikaryon. Finally, we speculate on relationships between plasmalemmal sealing, Wallerian degeneration, and the ability of polyethylene glycol (PEG) to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves. A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develop treatments for traumatic nerve injuries, stroke, muscular dystrophy, and other pathologies.

Key words: membrane damage, plasmalemmal sealing, vesicle mediated repair, Ca2+, axon regeneration, neuron