{"title":"The recruitment of mechanosensitive enteric neurons in the guinea pig gastric fundus is dependent on ganglionic stretch level.","authors":"Sophia Mayr, Kristin Elfers, Gemma Mazzuoli-Weber","doi":"10.1111/nmo.14858","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Serving as a reservoir, the gastric fundus can expand significantly, with an initial receptive and a following adaptive relaxation, controlled by extrinsic and intrinsic reflex circuits, respectively. We hypothesize that mechanosensitive enteric neurons (MEN) are involved in the adaptive relaxation, which is initiated when a particular gastric volume and a certain stretch of the stomach wall is reached. To investigate whether the responsiveness of MEN in the gastric fundus is dependent on tissue stretch, we performed mechanical stimulations in stretched versus ganglia \"at rest\".</p><p><strong>Methods: </strong>Responses of myenteric neurons in the guinea pig gastric fundus were recorded with membrane potential imaging using Di-8-ANEPPS. MEN were identified by small-volume intraganglionic injection in ganglia stretched to different degrees using a self-constructed stretching tool. Immunohistochemical staining identified the neurochemical phenotype of MEN. Hexamethonium and capsaicin were added to test their effect on recruited MEN.</p><p><strong>Key results: </strong>In stretched compared to \"at rest\" ganglia, significantly more MEN were activated. The change in the ganglionic area correlated significantly with the number of additional recruited MEN. The additional recruitment of MEN was independent from nicotinic transmission and the ratio of active MEN in stretched ganglia shifted towards a nitrergic phenotype.</p><p><strong>Conclusion and inferences: </strong>The higher number of active MEN with increasing stretch of the ganglia and their greater share of nitrergic phenotype might indicate their contribution to the adaptive relaxation. Further experiments are necessary to address the receptors involved in mechanotransduction.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurogastroenterology and Motility","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/nmo.14858","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Serving as a reservoir, the gastric fundus can expand significantly, with an initial receptive and a following adaptive relaxation, controlled by extrinsic and intrinsic reflex circuits, respectively. We hypothesize that mechanosensitive enteric neurons (MEN) are involved in the adaptive relaxation, which is initiated when a particular gastric volume and a certain stretch of the stomach wall is reached. To investigate whether the responsiveness of MEN in the gastric fundus is dependent on tissue stretch, we performed mechanical stimulations in stretched versus ganglia "at rest".
Methods: Responses of myenteric neurons in the guinea pig gastric fundus were recorded with membrane potential imaging using Di-8-ANEPPS. MEN were identified by small-volume intraganglionic injection in ganglia stretched to different degrees using a self-constructed stretching tool. Immunohistochemical staining identified the neurochemical phenotype of MEN. Hexamethonium and capsaicin were added to test their effect on recruited MEN.
Key results: In stretched compared to "at rest" ganglia, significantly more MEN were activated. The change in the ganglionic area correlated significantly with the number of additional recruited MEN. The additional recruitment of MEN was independent from nicotinic transmission and the ratio of active MEN in stretched ganglia shifted towards a nitrergic phenotype.
Conclusion and inferences: The higher number of active MEN with increasing stretch of the ganglia and their greater share of nitrergic phenotype might indicate their contribution to the adaptive relaxation. Further experiments are necessary to address the receptors involved in mechanotransduction.
背景:胃底作为一个蓄水池,可以显著扩张,最初的接受性松弛和随后的适应性松弛分别由外反射和内反射回路控制。我们假设机械敏感性肠神经元(MEN)参与了适应性松弛,当达到特定的胃容量和一定的胃壁伸展度时,适应性松弛就会启动。为了研究胃底肠肌神经元的反应性是否取决于组织的拉伸,我们对拉伸的神经节和 "静止 "的神经节进行了机械刺激:方法:使用 Di-8-ANEPPS 通过膜电位成像记录豚鼠胃底肠肌神经元的反应。在使用自制的拉伸工具拉伸到不同程度的神经节中,通过小容量节内注射确定 MEN。免疫组化染色确定了 MEN 的神经化学表型。加入六甲氧嗪和辣椒素以测试它们对招募的 MEN 的影响:主要结果:与 "静止 "神经节相比,拉伸神经节中被激活的 MEN 明显增多。神经节面积的变化与额外招募的 MEN 数量显著相关。额外招募的 MEN 与烟碱传导无关,拉伸神经节中活跃 MEN 的比例转向硝酸表型:结论和推论:随着神经节拉伸程度的增加,活性 MEN 的数量也随之增加,它们在能硝化表型中所占的比例也更大,这可能表明它们对适应性松弛做出了贡献。有必要进行进一步的实验来研究参与机械传导的受体。
期刊介绍:
Neurogastroenterology & Motility (NMO) is the official Journal of the European Society of Neurogastroenterology & Motility (ESNM) and the American Neurogastroenterology and Motility Society (ANMS). It is edited by James Galligan, Albert Bredenoord, and Stephen Vanner. The editorial and peer review process is independent of the societies affiliated to the journal and publisher: Neither the ANMS, the ESNM or the Publisher have editorial decision-making power. Whenever these are relevant to the content being considered or published, the editors, journal management committee and editorial board declare their interests and affiliations.