中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 251-252.doi: 10.4103/1673-5374.265547

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

多能干细胞衍生的抑制性中间神经元 - 健康和疾病的原理与应用

  

  • 出版日期:2020-02-15 发布日期:2020-05-23

Pluripotent stem cell derived inhibitory interneurons – principles and applications in health and disease

Francesca Keefe, Meng Li   

  1. Neuroscience and Mental Health Research Institute, School of Medicine and School of Bioscience, Cardiff University, Cardiff, UK
  • Online:2020-02-15 Published:2020-05-23
  • Contact: Francesca Keefe, KeefeF@cardiff.ac.uk; Meng Li, PhD, lim26@cardiff.ac.uk.
  • Supported by:
    This work was supported by grant from the UK Medical Research Council and EU Framework Programme 7 Repair-HD, to ML; FK is a recipient of a Wellcome Trust PhD studentship.

摘要: orcid: 0000-0001-7262-5307 (Francesca Keefe)

Abstract: Inhibitory interneurons are gamma-aminobutyric acid-ergic (GABAergic) nerve cells that act to maintain the appropriate excitation-inhibition balance, and synchronise the output of principle cells to generate rhythmic patterns of firing (Kessaris et al., 2014). This critical role, along with their brain-wide distribution, has led to the implication of interneurons in many neuropathologies, including schizophrenia, autism, dystonia and epilepsies (Marín, 2012). This has in turn fuelled a growing interest into their investigation. The molecular and functional heterogeneities within this class of neurons have resulted in a complex multifactorial classification system to assign interneurons into multiple subtypes (Figure 1A). Our journey towards understanding the interneuron diversity behind the classification system has brought to light the following principles. First, the subtype reflects the birthplace of the interneuron. Within the developing brain, inhibitory interneurons are born within focal regions, including the caudal and medial ganglionic eminences (CGE and MGE, respectively). Fate-mapping experiments in rodents demonstrated that calretinin (CR), vasoactive intestinal peptide and reelin positive interneurons are predominantly derived from CGE progenitors. Whereas, somatostatin (SST) and parvalbumin (PV) subtypes are MGE-derived, with an apparent SST: PV ratio shift along the MGE dorsoventral gradient (Kessaris et al., 2014). Second, interneuron subtypes exhibit differential vulnerability in neurological diseases (Marín, 2012). Third, there are brain region-specific differences in interneuron subtype composition, which are also species-dependent (Wu and Parent, 2000). The significance of these findings is unclear, as the manner to which interneuron lineages are determined by intrinsic and extrinsic cues remains under investigation (Kessaris et al., 2014).