Making 'sense' of what happens on the inside: il'LUMEN'ating the effects of intestinal distention on calcium activity in enteric neurons.
Making 'sense' of what happens on the inside: il'LUMEN'ating the effects of intestinal distention on calcium activity in enteric neurons.
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DOI：
10.1113/jp284397
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发表时间：
2023-04
影响因子：
5.5
通讯作者：
Cobine, Caroline A.
中科院分区：
文献类型：
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作者：
Cobine, Caroline A.
胃肠道（GI）负责食物的运动和消化，营养物质和水的吸收以及废物的排出。为了完成其功能，肠道受到外在和内在（肠）神经输入、间质细胞、巨噬细胞和神经胶质的影响。当食物被消化并通过肠道移动时，各种GI器官经历机械扭曲。包括Cajal间质细胞（ICC）、平滑肌细胞（SMC）、肠嗜铬细胞以及外源性和肠神经元在内的几种细胞类型响应于胃肠道扭曲（Alcaino等人，2017年）。在位于肌间神经丛和粘膜下神经丛内的神经元中，已经充分研究了拉伸和扩张的影响。已经描述或推断了内在初级传入神经元（IPAN）以及中间神经元（Spencer & Hu，2020）和运动神经元（Drokhlyansky等人，2020).以前的研究检查了机械变化对胃，小肠和结肠神经回路的影响。虽然这些研究为IPAN和中间神经元在拉伸诱导的变化中的作用提供了证据，但他们利用平板制备，其中粘膜或纵向肌肉被去除，分别用于专门检查粘膜下或肌间神经元群体。因此，有人可能会认为这可能并不能真实地反映体内发生的情况。遗传编码的Ca 2+指示剂如GCaMP和细胞特异性Cre系的可用性使得可以在包括肠神经元和神经胶质的多种细胞中成像Ca 2+信号（Boesmans等人，2018年）。在最新一期的生理学杂志上，Cavin和他的同事们（Cavin等人，2023）已经开发了一种方法来检查来自在所有肠神经元中表达GCaMP 6的小鼠（Wnt 1-GCaMP 6）的完整肠制备物的肠神经元内的Ca 2+信号传导和传播。这种方法有利于更好地再现肠神经元的自然环境。应该注意的是，尽管Wnt 1也在神经胶质中表达，但作者利用了复杂的实时3D成像方法，
The gastrointestinal (GI) tract is responsible for movement and digestion of food, absorption of nutrients and water and expulsion of waste. To accomplish its functions, the gut is influenced by extrinsic and intrinsic (enteric) neural inputs, interstitial cells, macrophages and glia. As food is digested and moved through the gut, the various GI organs undergo mechanical distortions. Several cell types including interstitial cells of Cajal (ICC), smooth muscle cells (SMCs), enterochromaffin cells and extrinsic and enteric neurons respond to GI tract distortions (Alcaino et al., 2017). The effects of stretch and distention have been well studied in neurons located within the myenteric and submucosal plexuses. Mechanosensitive properties have been described or inferred for intrinsic primary afferent neurons (IPANs) as well as interneurons (Spencer & Hu, 2020) and motor neurons (Drokhlyansky et al., 2020).Previous studies examined the effects of mechanical changes on the neural circuitry of the stomach, small intestine and colon. While these studies provided evidence for a role of IPANs and interneurons in stretch-induced changes, they utilized flat-sheet preparations in which either the mucosa or longitudinal muscle was removed for the purposes of specifically examining the submucosal or myenteric neuronal populations, respectively. Thus, one could argue that this may not truly reflect what occurs in vivo. The availability of genetically encoded Ca2+ indicators like GCaMP and cell-specific Cre lines have made it possible to image Ca2+ signals in a variety of cells including enteric neurons and glia (Boesmans et al., 2018). In the current issue of The Journal of Physiology, Cavin and colleagues (Cavin et al., 2023) have developed a method to examine Ca2+ signaling and propagation within enteric neurons of an intact intestinal preparation from mice expressing GCaMP6s in all enteric neurons (Wnt1-GCaMP6s). This approach is advantageous in better recapitulating the natural environment of enteric neurons. It should be noted that although Wnt1 is also expressed in glia, the authors utilized sophisticated live 3D imaging approaches, allowing