The gut-brain axis: spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon
The gut-brain axis: spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon
复制标题
DOI：
10.1152/ajpgi.00019.2022
复制
发表时间：
2022-05-01
影响因子：
4.5
通讯作者：
Spencer, Nick J.
中科院分区：
文献类型：
--
作者：
Dodds, Kelsi N.;Travis, Lee;Spencer, Nick J.
胃肠道和大脑之间的串扰对人类的健康和疾病具有重要的意义。然而，我们对肠道和大脑如何沟通的理解一直受到缺乏技术的限制，无法确定外部神经末梢之间的精确空间关系，以及它们与胃肠道内表面特定细胞类型的接近程度。我们使用我们实验室以前开发的体内顺行追踪技术，选择性地标记小鼠结肠粘膜中的单个脊髓传入轴突及其神经末梢。然后测量脊髓传入神经末梢和轴索静脉曲张到含有5-羟色胺(5-羟色胺；5-羟色胺)的肠嗜铬(EC)细胞之间的最近三维距离。脊髓传入轴索或神经末梢的静脉曲张与EC细胞之间的平均距离(+/-标准差)分别为5.7+/-6.0微米(中位数：3.6微米)和26.9+/-18.6微米(中位数：24.1微米)。EC细胞的空间位置的随机化显示了与实际数据相似的结果。这些距离大约是脊椎动物神经系统突触传递的突触前膜和突触后膜(15-25 nm)之间距离的200-1000倍。我们的发现表明，结肠内含5-羟色胺的EC细胞释放物质，可能通过扩散激活中枢投射的脊髓传入神经，因为这种信号不太可能在突触的空间保真度下发生。新和值得注意的是，在小鼠结肠粘膜中，脊髓传入神经和含5-羟色胺的EC细胞之间没有密切的物理接触。与实际数据相比，随机的EC细胞和脊髓传入细胞之间的相对距离相似。这种空间关系表明，含有5-羟色胺的结肠EC细胞释放的物质不太可能通过突触传递到邻近的脊髓传入，后者将感觉信息从肠腔传递到大脑。
Cross talk between the gastrointestinal tract and brain is of significant relevance for human health and disease. However, our understanding of how the gut and brain communicate has been limited by a lack of techniques to identify the precise spatial relationship between extrinsic nerve endings and their proximity to specific cell types that line the inner surface of the gastrointestinal tract. We used an in vivo anterograde tracing technique, previously developed in our laboratory, to selectively label single spinal afferent axons and their nerve endings in mouse colonic mucosa. The closest three-dimensional distances between spinal afferent nerve endings and axonal varicosities to enterochromaffin (EC) cells, which contain serotonin (5-hydroxytryptamine; 5-HT), were then measured. The mean distances (+/- standard deviation) between any varicosity along a spinal afferent axon or its nerve ending, and the nearest EC cell, were 5.7 +/- 6.0 mu m (median: 3.6 mu m) and 26.9 +/- 18.6 mu m (median: 24.1 mu m), respectively. Randomization of the spatial location of EC cells revealed similar results to this actual data. These distances are similar to 200-1,000 times greater than those between pre- and postsynaptic membranes (15-25 nm) that underlie synaptic transmission in the vertebrate nervous system. Our findings suggest that colonic 5-HT-containing EC cells release substances to activate centrally projecting spinal afferent nerves likely via diffusion, as such signaling is unlikely to occur with the spatial fidelity of a synapse.NEW & NOTEWORTHY We show an absence of close physical contact between spinal afferent nerves and 5-HT-containing EC cells in mouse colonic mucosa. Similar relative distances were observed between randomized EC cells and spinal afferents compared with actual data. This spatial relationship suggests that substances released from colonic 5-HT-containing EC cells are unlikely to act via synaptic transmission to neighboring spinal afferents that relay sensory information from the gut lumen to the brain.