中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (12): 1940-1942.doi: 10.4103/1673-5374.169625

• 观点:脊髓损伤修复保护与再生 • 上一篇    下一篇

脊髓运动的代谢补充:示踪胺及其受体的细胞内神经调节 

  

  • 收稿日期:2015-09-25 出版日期:2015-12-30 发布日期:2015-12-30
  • 基金资助:

    这项工作是由美国国家科学基金会IOS-0745164;美国瘫痪退伍军人中心;克雷格?尼尔森基金会; NINDS F31 NS057911-02支持

Metabolic recruitment of spinal locomotion: intracellular neuromodulation by trace amines and their receptors

Shawn Hochman*   

  1. Department of Physiology Department, Emory University, Atlanta, GA, USA
  • Received:2015-09-25 Online:2015-12-30 Published:2015-12-30
  • Contact: Shawn Hochman, Ph.D., shawn.hochman@gmail.com.
  • Supported by:

    This work was supported by NSF IOS-0745164; Paralyzed Veterans of America; Craig H Neilsen Foundation.

摘要:

示踪胺,包括一类由相同前体氨基酸和必需合成酶组成的系列合成神经活性单胺,是经典的单胺调节递质。经典神经递质是人们长期研究的一些小分子化合物,已经明确的有乙酰胆碱;单胺类、氨基酸类。这些神经递质通过传递各种信息而实现调节机体生理功能的作用。
文章重新评估了示踪胺与脊髓损伤后运动功能恢复作用的关系,Shawn Hochman教授首先对示踪胺进行了简单的概述:由于缺乏存储空间,示踪胺的示踪探测能力不仅导致它们很难归因于中枢神经系统功能,也容易因为作用表达不稳而成为废弃的代谢产物。2001年发现的G-蛋白偶联示量胺相关受体由示踪胺优先激活,因此建立了示踪胺自身的效果机制,并引发针对G-蛋白偶联示量胺相关受体作为脑单胺能信令一个组成部分的新研究。尽管如此,如果不能识别胺能神经元回路离散痕迹,它们在中枢神经系统中的调节作用就仍然不明朗;在新生大鼠脊髓中示踪胺能够促进脊髓运动模式的独立表达。其他的研究结果表明,示踪胺作为一类独特的内在神经调节单胺类元素可进行细胞内活动。在肌肉紧张的脊髓电路兴奋条件下,示踪胺对行为的功能相关性可以作为自适应胞内代谢效应器。最后作者强调的是,需要有更多的实验来验证示踪胺的作用,包括继发性调节成人脊髓损伤的运动电路,例如,其后表达可促进脊髓功能的可能神经治疗方法。

Abstract:

The trace amines (TAs) comprise a class of neuroactive monoamines that are synthesized from the same precursor amino acids and essential synthesis enzyme as the classical monoamine modulatory transmitters [Figure 1]. This perspective report re-appraises their role in relation to our recent findings on their unique motor facilitatory actions. (1) I first provide an overview of the TAs. Their detectability in trace amounts due to lack of storage led not only to their name but also to an expression lability that made it difficult to ascribe a role in CNS function but easy to dismiss as metabolic byproducts. The 2001 discovery of G-protein coupled trace amine-associated receptors (TAARs) preferentially activated by TAs established a mechanisms by which TAs can produce effects of their own, and inspired new investigations that placed the TAAR1 receptor as a component of brain monoaminergic signaling. Still, without identification of discrete trace aminergic neuronal circuits, their role in CNS modulation remains uncertain.(2) I then describe our results in the neonatal rat spinal cord showing that the TAs can facilitate expression of spinal locomotor patterns independent of, but with comparable ability to, descending monoamines. Additional results support the TAs as a distinct class intrinsic monoaminergic neuromodulators acting intracellularly, putatively on TAARs. (3)The functional relevance of the TAs to behavior is then explored as an adaptive intracellular metabolic effector, and in tonically setting spinal circuit excitability. (4) Finally, emphasis on the need for additional experiments including in the adult segues into possible neurotherapeutic approaches that modulate spinal cord function with facilitated expression of locomotor circuits after spinal cord injury as an example.