中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (11): 2198-2200.doi: 10.4103/1673-5374.310683

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

寻找替代大脑再生的方法

  

  • 出版日期:2021-11-15 发布日期:2021-04-13

Searching for alternatives to brain regeneration

Chiara La Rosa, Luca Bonfanti   

  1. Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, Italy (La Rosa C, Bonfanti L) 
    Department of Veterinary Sciences, University of Turin, Grugliasco, Italy (Bonfanti L)
  • Online:2021-11-15 Published:2021-04-13
  • Contact: Luca Bonfanti, DVM, PhD, luca.bonfanti@unito.it.
  • Supported by:
    We thank Richard Vernell for overall English revision. 

摘要:

Neural Regen Res:干细胞驱动成年哺乳动物的神经发生和脑可塑性

    成人神经发生自最初发现以来,一直被认为是我们理解大脑再生的一个转折点。大多数哺乳动物的大脑至少有两个活跃的神经发生部位,其中多能神经干细胞产生新的神经元,能够在有限的大脑区域内成熟和进行功能整合。很明显哺乳动物的神经干细胞龛只产生少数类型的神经元,这些神经元选择性地整合在非常特殊的神经回路中。此外,宿主干细胞的神经源性部位在动物的整个生命周期中数量和活性逐渐减少。这种减少发生在包括人类在内的大脑哺乳动物的早期,在那里它导致干细胞龛在青春期大量耗尽。尽管大多数科学家仍然认为成人神经发生是大脑修复的潜在神经元来源,但它似乎是一种生理“工具”,使参与生存相关任务(食物搜索/识别、识别捕食者、学习、记忆、繁殖)的神经回路能够适应不断变化的环境。哺乳动物的成年神经发生似乎属于“结构可塑性”而不是“脑再生”,因此,属于生理可塑性而不是脑修复机制。大脑袋长寿命的物种似乎保持着不同的结构可塑性,以提供渐进的大脑成熟,而不是再生,随着年龄和大脑区域的不同而有很大的变化。

    来自意大利都灵大学的Luca Bonfanti团队认为真正的大脑再生发生在某些非哺乳动物脊椎动物的神经系统,在哺乳动物的大脑中,特别是在成人中,这种再生大大减少。成年哺乳动物神经干细胞的发生仅限于特定区域,主要与嗅球和海马在出生后发育过程中的逐渐完成有关。在大脑袋物种中,新皮质的显著扩张与非新生的未成熟神经元(也在皮质下区域)的增加似乎是平行的,这些神经元在胚胎发生期间形成,不能在出生后分裂,但随着时间的推移保留未分化的特征。关于哺乳动物大脑中这种新形式的可塑性,仍有许多问题,特别是关于这些细胞的生理作用、它们的最终命运,以及它们“静止”和诱导它们成熟的机制。目前还不知道它们是否能对病变/病理学做出反应,或是受到外部线索的调节,仍然不知道它们在人脑中的丰富程度。如果类似的细胞在人类中广泛存在,就像它们在其他大脑袋物种中一样,它们可能代表了所谓的“大脑储备”或“认知储备”的基底,以抵御痴呆症和神经退行性疾病的发生/影响。

    文章《中国神经再生研究(英文版)》杂志202111 月  11 期发表。

https://orcid.org/0000-0002-1469-8898 (Luca Bonfanti)

Abstract: Brain regeneration from an evolutionary perspective: Brain regeneration (the full restoration of tissue after loss from injury or disease) is the most sought after goal for researchers working in developmental neurobiology. It also appears to be the most challenging to achieve when considering the mammalian brain. Whereas remarkable regenerative capacities can be present in the central nervous systems of many non-mammalian vertebrates (e.g., fish, amphibians), these kinds of processes appear to be dramatically reduced in mammals (Bonfanti, 2011). The reasons for such differences across animal classes are not completely understood, yet, some clear aspects have emerged from the study of well-established models like the teleost fish brain (Lange and Brand, 2020), which has: i) multiple, widespread stem cell niches that provide continuous, physiological cell renewal, as well as regeneration after lesioning; ii) additional neural elements that can de-differentiate after injury and re-acquire stem cell properties; iii) the ability to re-activate developmental programs in order to provide regenerative capacity. Studies on regeneration in various tissues and organs across animal species indicate that physiological and lesion-induced regeneration requires the coexistence of some (if not all) of the above-mentioned aspects, which, in the mammalian brain, are either absent or restricted to very small neurogenic niches. The most intuitive explanation for differences in brain regeneration across animal classes, apart from causal reasons, is the need for more neuroanatomical complexity linked to increased computational capabilities that often occurs in parallel with increased brain size. The “complexity” of large brains appears to be incompatible with substantial cell renewal/regeneration, a process that would be biologically expensive and somehow in contrast with the requirement for “stability” of the neural circuits (e.g., to retain long-term memories related to multiple previous experiences in long-living organisms). The current state of knowledge is still a mix of evidence and theories that are blurred by the frequently irregular patterns of evolution, but it does point to an important, underestimated issue: phylogenetic variations in the location, amount, rate, and type of brain plasticity in mammals.