Cultured Vagal Afferent Neurons as Sensors for Intestinal Effector Molecules.
Cultured Vagal Afferent Neurons as Sensors for Intestinal Effector Molecules.
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DOI：
10.3390/bios13060601
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发表时间：
2023-05-31
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肠-脑轴体现了胃肠道和中枢神经系统（CNS）之间的双向通信，其中迷走传入神经元（VAN）充当各种肠源性信号的传感器。肠道由大量不同的微生物群体定殖，这些微生物群体通过小（效应）分子进行通信，这些小分子也作用于位于肠道内脏中的货车末端，从而影响许多CNS过程。然而，复杂的体内环境使得难以研究效应分子对货车激活或脱敏的因果影响。在这里，我们报告了一个货车文化和它的原理证明示范作为一个基于细胞的传感器，以监测胃肠效应分子对神经元行为的影响。我们最初比较了表面涂层（聚-L-赖氨酸与基质胶）和培养基组合物（血清与生长因子补充剂）对神经突生长的影响，作为组织收获后货车再生的替代物，其中基质胶涂层而不是培养基组合物在增加的神经突生长中起重要作用。然后，我们使用活细胞钙成像和细胞外电生理记录表明，VAN响应于经典的内源性和外源性来源的效应分子（胆囊收缩素5-羟色胺和辣椒素）在一个复杂的方式。我们希望这项研究能够筛选各种效应分子及其对货车活性的影响，通过其丰富的电生理指纹信息进行评估。
The gut–brain axis embodies the bi-directional communication between the gastrointestinal tract and the central nervous system (CNS), where vagal afferent neurons (VANs) serve as sensors for a variety of gut-derived signals. The gut is colonized by a large and diverse population of microorganisms that communicate via small (effector) molecules, which also act on the VAN terminals situated in the gut viscera and consequently influence many CNS processes. However, the convoluted in vivo environment makes it difficult to study the causative impact of the effector molecules on VAN activation or desensitization. Here, we report on a VAN culture and its proof-of-principle demonstration as a cell-based sensor to monitor the influence of gastrointestinal effector molecules on neuronal behavior. We initially compared the effect of surface coatings (poly-L-lysine vs. Matrigel) and culture media composition (serum vs. growth factor supplement) on neurite growth as a surrogate of VAN regeneration following tissue harvesting, where the Matrigel coating, but not the media composition, played a significant role in the increased neurite growth. We then used both live-cell calcium imaging and extracellular electrophysiological recordings to show that the VANs responded to classical effector molecules of endogenous and exogenous origin (cholecystokinin serotonin and capsaicin) in a complex fashion. We expect this study to enable platforms for screening various effector molecules and their influence on VAN activity, assessed by their information-rich electrophysiological fingerprints.
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影响因子：
4.3
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