中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1253-1254.doi: 10.4103/1673-5374.327337

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

5-羟色胺在调节成年出生的嗅球神经元发育和功能中的作用

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Role of serotonin in modulating the development and function of adult-born neurons in the olfactory bulb

Natalie Fomin-Thunemann, Olga Garaschuk*   

  1. Department of Biomedical Engineering, Boston University, Boston, MA, USA (Fomin-Thunemann N) 
    Institute of Physiology, Department Neurophysiology, Eberhard Karls University of Tübingen, Tübingen, Germany (Garaschuk O)
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Olga Garaschuk, PhD, olga.garaschuk@uni-tuebingen.de.
  • Supported by:
    The present work was supported by the German Research Foundation (DFG) grant GA 654/14-1 to OG.

摘要: Neural Regen Res:5-羟色胺信号对成人神经发生的区域特异性影响 
神经调节递质5-羟色胺由位于脑干中的神经元合成,这些神经元密集地投射到整个中枢神经系统。5-羟色胺调节多种生理功能,包括食物摄入、奖赏、繁殖、睡眠-觉醒周期、记忆、认知和情绪。5-羟色胺能系统的功能障碍与精神障碍的发生或进展有关,包括自闭症、失眠、焦虑、抑郁、精神分裂症、帕金森病或阿尔茨海默病。前期研究表明成人神经发生和嗅觉记忆受到氟西汀(一种抗抑郁药和选择性血清素再摄取抑制剂)的正向调节。5-羟色胺在成人神经发生中具有特定作用,因为5-羟色胺在整个生命过程中调节成人出生细胞的命运和功能状态。5-羟色胺能投射支配海马体和嗅球以及它们各自的神经源性生态位,颗粒下区和脑室下区。支配嗅球的 5-羟色胺能纤维源自背侧和中缝核,主要支配嗅球的浅表肾小球层,颗粒和二尖瓣细胞层的神经支配较稀疏。球茎的肾小球层的 5-羟色胺神经支配并不均匀,因为相邻肾小球之间支配 5-羟色胺的纤维密度和厚度不同。在脑室下区的神经源性生态位内,5-羟色胺输入沿着侧脑室壁运行。在这里,放射状胶质细胞(B 细胞)产生瞬时放大细胞(C 细胞),然后产生成神经细胞。5-羟色胺促进脑室下区中 B 和 C 细胞的增殖。
来自美国波士顿大学的Olga Garaschuk团队认为, 5-羟色胺能末端的损伤或5-羟色胺合成的抑制导致脑室下区中BrdU阳性(BrdU+)成人出生细胞的数量显着减少,同时将释放5-羟色胺的药物芬氟拉明输注到成年小鼠侧脑室显着增加了脑室下区中BrdU+ 成年出生细胞和双皮质素阳性神经母细胞的数量。5-HT1A 和 5-HT2C 受体激动剂增加,而 5-HT2C 受体拮抗剂降低成年小鼠脑室下区中的细胞增殖。5-羟色胺的应用会在 B 细胞中诱导去极化内向电流,该电流被 5-HT2C 或 5-HT5A 受体拮抗剂部分阻断。 5-HT2C 和 5-HT5A 受体拮抗剂的共同应用完全消除了B细胞中血清素诱导的电流。这些数据强调了5-羟色胺在控制脑室下区增殖和神经发生方面的重要性。总之,5-羟色胺能输入支持哺乳动物大脑的两个神经源性生态位中成体神经发生的主要步骤,包括细胞增殖、迁移和存活。即使在成人出生的细胞完全整合到周围的神经回路并在其中成熟之后,5-羟色胺输入也会向成人细胞传递独特的功能特性,使它们能够以大脑特异性方式在整合环境刺激方面发挥独特的作用 .
    文章在《中国神经再生研究(英文版)》杂志2022年 6 月  6 期发表。 

Abstract: The neuromodulatory transmitter serotonin (5-hydroxytryptamine, 5-HT) is synthesized by neurons located in the brainstem, which project more or less densely to the entire central nervous system (Charnay and Leger, 2010). Serotonin regulates a variety of physiological functions, including food intake, reward, reproduction, sleep-wake cycle, memory, cognition, emotion, and mood (Charnay and Leger, 2010). Consistently, dysfunctions of the serotonergic system are involved in the development or progression of mental disorders including autism, insomnia, anxiety, depression, schizophrenia, Parkinson’s disease, or Alzheimer’s disease (Charnay and Leger 2010). Many of these diseases (e.g., autism, schizophrenia, depression, Parkinson’s disease, Alzheimer’s disease) present with concomitant impairment of olfaction (and memory), often accompanied by a reduced volume of the olfactory bulb (OB; Figure 1A) and hippocampus. These functional impairments may result from distorted adult neurogenesis in the respective neurogenic niches, as OB and hippocampal dentate gyrus are the two major areas of the adult mammalian brain where adult-born cells are generated throughout life. A wide range of studies documents the involvement of adult-born cells in short- and long-term olfactory memory; perceptual, associative, and fear learning, etc. (summarized in Lepousez et al., 2015; Fomin-Thunemann et al., 2020).