Department of Integrative Biology, Michigan State University, East Lansing, MI 48824, USA.
Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Int J Mol Sci. 2022 Apr 27;23(9):4799. doi: 10.3390/ijms23094799.
The neural-crest-derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS disorders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed understanding of how regeneration is regulated on a cellular and molecular level in animal models with both high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.
神经嵴衍生的肠神经系统 (ENS) 是胃肠道的内在神经系统，控制所有肠道功能，包括运动。ENS 神经元的缺失会导致各种 ENS 疾病，如先天性巨结肠症。ENS 疾病的一种治疗选择包括激活固有干细胞来再生 ENS 神经元。ENS 的再生主要在哺乳动物物种中使用手术或化学诱导损伤方法进行研究。这些哺乳动物研究显示出各种再生反应，通常 ENS 神经元的再生有限，但神经纤维有（部分）再生和功能恢复。多种因素可能导致再生反应的多样性，包括损伤后的观察时间、物种和靶向的肠道区域。斑马鱼最近成为研究 ENS 再生的有前途的模型系统，因为幼虫在消融后有产生新神经元的能力。作为 ENS 再生研究的下一步，我们需要详细了解在具有高和低再生能力的动物模型中，细胞和分子水平上的再生是如何调节的。了解 ENS 再生所需的调节程序将为利用神经再生作为治疗 ENS 疾病的治疗方法铺平道路。
