3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury
3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury
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DOI：
10.1007/s00125-012-2699-6
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发表时间：
2012-12-01
期刊：
影响因子：
8.2
通讯作者：
Tang, S. -C.
中科院分区：
文献类型：
--
作者：
Chiu, Y. -C.;Hua, T. -E.;Tang, S. -C.
交感神经影响循环中的胰岛激素水平。深入了解胰岛交感神经支配及其在糖尿病中的重塑可能会影响未来的治疗方法。然而，标准的免疫组织化学和基于切片的显微镜检查不能提供胰岛神经血管复合体的完整视图。制备透明胰岛标本，观察正常小鼠、链脲佐菌素注射小鼠和非肥胖糖尿病小鼠模型的交感神经、血管和胰岛细胞的空间关系，用荧光凝集素心脏灌注法标记胰腺血管。酪氨酸羟化酶染色和细胞核染色显示胰岛交感神经支配和显微结构。光学清除（即使用浸泡溶液，以减少散射），使三维共聚焦显微镜的胰岛可视化的交感神经血管复合体在space. Different以前报道的形态，我们观察到灌注内胰岛，血管周围的交感神经支配，除了胰岛周围的交感神经与α细胞和交感神经纤维环绕相邻的小动脉的接触。在注射链脲佐菌素的小鼠中，胰岛内轴突变得明显突出（注射后2周）。在非肥胖糖尿病小鼠中，淋巴细胞浸润在早期胰岛炎中重塑了胰岛周围的交感神经轴突。我们建立了一种成像方法来显示小鼠胰岛交感神经支配的空间特征。神经血管复合体和交感神经-α细胞接触表明，交感神经除了直接作用于α细胞外，还通过血管调节胰岛激素分泌。在胰岛损伤中，交感神经响应于不同的病理生理学线索而经历不同的重构。
Sympathetic nerves influence islet hormone levels in the circulation. Insights into islet sympathetic innervation and its remodelling in diabetes may impact future therapeutics. However, standard immunohistochemistry and microtome-based microscopy cannot provide an integral view of the islet neurovascular complex. We prepared transparent islet specimens to investigate the spatial relationship between sympathetic nerves, blood vessels and islet cells in normal, streptozotocin-injected and non-obese diabetic mouse models.Cardiac perfusion of fluorescent lectin was used to label pancreatic blood vessels. Tyrosine hydroxylase and nuclear staining were used to reveal islet sympathetic innervation and microstructure. Optical clearing (i.e. use of immersion solution to reduce scattering) was applied to enable 3-dimensional confocal microscopy of islets to visualise the sympathetic neurovascular complex in space.Unlike previously reported morphology, we observed perfusive intra-islet, perivascular sympathetic innervation, in addition to peri-islet contacts of sympathetic nerves with alpha cells and sympathetic fibres encircling the adjacent arterioles. The intra-islet axons became markedly prominent in streptozotocin-injected mice (2 weeks after injection). In non-obese diabetic mice, lymphocytic infiltration remodelled the peri-islet sympathetic axons in early insulitis.We have established an imaging approach to reveal the spatial features of mouse islet sympathetic innervation. The neurovascular complex and sympathetic nerve-alpha cell contact suggest that sympathetic nerves modulate islet hormone secretion through blood vessels, in addition to acting directly on alpha cells. In islet injuries, sympathetic nerves undergo different remodelling in response to different pathophysiological cues.