Periglomerular afferent innervation of the mouse renal cortex.

Periglomerular afferent innervation of the mouse renal cortex.
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DOI:
10.3389/fnins.2023.974197
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发表时间:
2023
影响因子:
4.3
通讯作者:
Osborn, John W. W.
Osborn, John W. W.
中科院分区:
医学2区
文献类型:
--
作者:
Tyshynsky, Roman;Sensarma, Sulagna;Riedl, Maureen;Bukowy, John;Schramm, Lawrence P. P.;Vulchanova, Lucy;Osborn, John W. W.

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最近的研究使用一种新的方法来靶向消融肾传入神经,已经证明了它们在一些高血压动物模型的发展和维持中的重要性。然而,对于肾盂远端肾传入神经的解剖,我们所知相对较少。在这里,我们研究了肾小球和传入轴突之间的解剖关系,这些关系是基于瞬时受体电位香草碱样蛋白1通道(TRPV1)谱系或降钙素基因相关肽(CGRP)免疫标记来确定的。对来自野生型C57BL/6J小鼠和TRPV1谱系细胞中表达tdTomato的转基因小鼠的6000多个肾小球的分析表明,大约一半的肾小球与tdTomato+或CGRP+传入轴突密切相关。肾小球根据其在皮层内的深度分为浅表性、皮质中性或近髓性。近髓肾小球比浅表肾小球更可能与传入轴突亚型紧密相连。厚的、清晰的肾片的高分辨率成像和随后的距离转换显示,在肾小球足细胞nephrin+标记的2微米范围内,经常发现与肾小球密切相关的CGRP+轴突。此外,厚片成像显示CGRP+轴突束可以紧密靠近共享同一小叶间动脉的多个肾小球。基于CGRP或tdTomato的表达,肾小球附近的患病率,靠近肾小球结构,以及在一个模块内靠近多个肾小球,我们假设肾小球周围传入轴突可能具有监测肾小球压力的机械感受器功能。这些解剖学发现强调了进一步研究肾小球周围传入轴突在健康和疾病中肾脏功能的神经控制中的生理作用的重要性。
Recent studies using a novel method for targeted ablation of afferent renal nerves have demonstrated their importance in the development and maintenance of some animal models of hypertension. However, relatively little is known about the anatomy of renal afferent nerves distal to the renal pelvis. Here, we investigated the anatomical relationship between renal glomeruli and afferent axons identified based on transient receptor potential vanilloid 1 channel (TRPV1) lineage or calcitonin gene related peptide (CGRP) immunolabeling. Analysis of over 6,000 (10,000 was accurate prior to the removal of the TH data during the review process) glomeruli from wildtype C57BL/6J mice and transgenic mice expressing tdTomato in TRPV1 lineage cells indicated that approximately half of all glomeruli sampled were closely apposed to tdTomato+ or CGRP+ afferent axons. Glomeruli were categorized as superficial, midcortical, or juxtamedullary based on their depth within the cortex. Juxtamedullary glomeruli were more likely to be closely apposed by afferent axon subtypes than more superficial glomeruli. High-resolution imaging of thick, cleared renal slices and subsequent distance transformations revealed that CGRP+ axons closely apposed to glomeruli were often found within 2 microns of nephrin+ labeling of glomerular podocytes. Furthermore, imaging of thick slices suggested that CGRP+ axon bundles can closely appose multiple glomeruli that share the same interlobular artery. Based on their expression of CGRP or tdTomato, prevalence near glomeruli, proximity to glomerular structures, and close apposition to multiple glomeruli within a module, we hypothesize that periglomerular afferent axons may function as mechanoreceptors monitoring glomerular pressure. These anatomical findings highlight the importance of further studies investigating the physiological role of periglomerular afferent axons in neural control of renal function in health and disease.
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