中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 388-389.doi: 10.4103/1673-5374.179037

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

我们通过预处理可以保护脑神经元吗?

  

  • 收稿日期:2015-12-29 出版日期:2016-03-15 发布日期:2016-03-15

Can we protect the brain via preconditioning? Role of microRNAs in neuroprotection

Sean Quinlan, Eva M. Jimenez-Mateos   

  1. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland
  • Received:2015-12-29 Online:2016-03-15 Published:2016-03-15
  • Contact: Eva M. Jimenez-Mateos, Ph.D.,evajimenez@rcsi.ie.

摘要:

预处理是一种适应性反应,即少量有害物质保护大脑免受随后的破坏性损伤。预处理诱导神经保护有两个阶段:第一阶段,快速耐受,这一阶段发生周期很短,有独立蛋白质生产,并且与突触重塑有关。第二阶段,延迟(经典)耐受,这一演变过程通常为1-3天。文章主要展示了微小RNA:一种小非编码RNA(长度在20-22个核苷酸),可以调节特异性方式转录后水平后的基因表达序列。微小RNA在中枢神经系统中有着大量表达并参与多种功能,包括神经细胞迁移和分化,突触可塑性以及功能维护。微小RNA在脑组织预处理中的作用已经在几个实验模型,包括缺血性癫痫小鼠模型中进行了分析。在这些研究中,几个微小RNA已被确定为是预处理刺激神经保护作用的介体。微小RNA调控通路与从头-蛋白合成调节相关,支持从头-蛋白质合成和大脑中预处理处理效率及预处理关联的原始发现。现在亟需解决的一个主要问题是如何还原中枢神经系统原始生物情况的周边轮廓。并且更深入的研究应该是必要的,以评估循环微小RNA和神经生理状况之间的相关性。

Abstract:

Preconditioning is an adaptive response, whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult. Consequently, several preconditioning treatment paradigms are used in the clinic to protect patients against an ischemic insult in heart pathologies. This data shows the importance of understanding the underlying mechanism to preconditioning, and its translation in the clinic in brain disorders. In concordance, any injury to the brain applied below the threshold of cell damage, including seizures, will induce preconditioning and neuro-protection to the brain. Preconditioning can induce neuroprotection over two phases: Phase one, rapid tolerance, this occurs in a short period of time and is independent of protein production and associated with synapse remodelling. Phase two, delayed (classical) tolerance, this evolves over 1-3 days and requires de novo protein production with a peak at 3 days and diminishes over the course of 1 week. MicroRNAs are defined as small non-coding RNAs (~ 20-22 nucleotides) that regulate gene expression at a post-transcriptional level in a sequence-specific manner. MiRNAs are abundantly expressed in the central nervous system, being involved in diverse functions, including neuronal migration and differentiation, synaptic plasticity and maintenance of functions. The role of microRNAs in preconditioning in brain has been analysed in several experimental models, including ischemic and epileptic murine models. In these studies several microRNAs have been identified as mediators of the neuro-protected effect of the preconditioning stimulus. Both microRNAs regulated pathways are associated with de novo-protein synthesis regulation, supporting the original findings of the association of preconditioning with the de novo-protein synthesis and the efficiency of the preconditioning treatment in the brain. One major question is how faithful is the peripheral profile to the original biological situation in the CNS. However, the same microRNA will not be used as a biomarker and therapeutics target. But still, more deep studies should be necessary to evaluate the correlation between the circulating microRNAs and the neuro-physiological condition.