Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room
Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room
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DOI：
10.1159/000447084
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
B. Beltz;Georg Brenneis;J. Benton
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文献类型：
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作者：
B. Beltz;Georg Brenneis;J. Benton
甲壳动物大脑中的第一代神经前体在功能上类似于哺乳动物中的神经干细胞。它们的缓慢循环、后代的迁移以及后代在数周内分化为神经元是小龙虾神经前体谱系的特征，也是哺乳动物成体神经发生的特征。然而，小龙虾中的第一代前体细胞不会自我更新，这与传统观点提出的成体神经干细胞的长期自我更新形成鲜明对比。尽管如此，小龙虾的神经原生态位，总共包含200-300个细胞，永远不会耗尽，神经元在动物的一生中继续在大脑中产生。因此，生态位中的神经前体池不可能是一个封闭的系统，必须从外部来源补充。我们的体外和体内数据表明，起源于先天免疫系统的细胞（而不是其他类型的细胞）被吸引到神经原性小生境中并被纳入其中，并且它们表达小生境特异性标记物谷氨酰胺合成酶。此外，经过过继转移到受体小龙虾的标记血细胞在成年大脑的嗅觉通路中产生神经元簇中的细胞。这些血细胞后代表达适当的神经递质，并投射到这些区域中典型的神经元靶向区域。这些研究表明，在自然条件下，免疫系统提供神经前体支持小龙虾大脑中的成年神经发生，挑战了产生胚胎神经系统的外胚层组织是成年大脑中神经元的唯一来源的经典观点。然而，这些并不是第一个直接涉及免疫系统作为神经前体细胞来源的研究。哺乳动物中的几种类型的数据，包括骨髓或干细胞的过继转移以及胎儿微嵌合体的存在，表明必须有一群细胞能够进入大脑并在这些物种中产生新的神经元。
The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.