Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons.
Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons.
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DOI：
10.1016/j.neuroscience.2014.10.043
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发表时间：
2015-01-22
期刊：
影响因子：
3.3
通讯作者：
Trapp, S.
中科院分区：
文献类型：
--
作者：
Llewellyn-Smith, I. J.;Marina, N.;Manton, R. N.;Reimann, F.;Gribble, F. M.;Trapp, S.
关键词：
脊髓 GLP-1 轴突主要靶向交感神经节前神经元。脊髓 GLP-1 轴突支配可调节交感神经流出的中间神经元。髓质中的许多 GLP-1 神经元是脊髓突出的。腰脊髓含有表达 YFP 的神经元，不支配大脑。胰高血糖素样肽-1 (GLP-1) 影响中枢自主神经元，包括控制心血管系统、产热和能量平衡的神经元。前胰高血糖素 (PPG) 神经元主要位于孤束核 (NTS) 和髓质网状结构中，产生 GLP-1。在表达胰高血糖素启动子驱动的黄色荧光蛋白 (YFP) 的转基因小鼠中，这些脑干 PPG 神经元投射到许多表达 GLP-1 受体的中央自主区域。脊髓也含有 GLP-1 受体 mRNA，但脊髓 PPG 轴突的分布尚不清楚。在这里，我们使用双色免疫过氧化物酶标记来检查 YFP-PPG 小鼠脊柱 T1-S4 节段的 PPG 神经支配。 YFP 的免疫反应性鉴定出脊髓 PPG 轴突和核周。我们根据从腹膜腔逆行转运的胆碱乙酰转移酶（ChAT）、一氧化氮合酶（NOS）和/或氟金（FG）的免疫反应性对接收 PPG 输入的脊髓神经元进行分类。在 T9 定义的细胞体处显微注射 FG，提供脊髓 PPG 神经支配。下腰脊髓的深部背角含有 YFP 免疫反应性神经元。非静脉曲张、YFP 免疫反应性轴突在外侧索、腹侧白连合和腹侧正中裂周围突出。在 T1-L2 中，曲张的、含有 YFP 的轴突与中间外侧细胞柱 (IML) 和背板 X 中的许多 ChAT 免疫反应性交感神经节前神经元 (SPN) 紧密并列。在骶副交感神经核中，约 10% 的 ChAT 免疫反应性节前神经元接受 YFP 并置，整个神经节中偶尔出现 ChAT 阳性运动神经元也是如此。腹角的吻尾范围。 YFP 并置也发生在 NOS 免疫反应性脊髓中间神经元和脊髓 YFP 免疫反应性神经元上。在 T9 处注射 FG 逆行标记髓质中的许多 YFP-PPG 细胞体，但没有标记脊髓 YFP 免疫反应性神经元。这些结果表明脑干 PPG 神经元支配脊髓自主神经和躯体运动神经元。脊髓 PPG 轴突和脊髓 GLP-1 受体的分布具有良好的相关性。 SPN 接受最密集的 PPG 神经支配。脑干 PPG 神经元可以通过其脊髓输入直接调节交感神经流出到 SPN 或中间神经元。
Spinal GLP-1 axons target primarily sympathetic preganglionic neurons. Spinal GLP-1 axons innervate interneurons that may regulate sympathetic outflow. Many GLP-1 neurons in the medulla are spinally-projecting. The lumbar cord contains YFP-expressing neurons that do not innervate the brain. Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons.
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DOI：
10.1523/jneurosci.3262-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dossat AM;Lilly N;Kay K;Williams DL
通讯作者：
Williams DL
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Llewellyn-Smith, I. J.;Gnanamanickam, G. J. E.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
影响因子：
3.3
作者：
Larsen, PJ;TangChristensen, M;Orskov, C
通讯作者：
Orskov, C
影响因子：
4.8
作者：
Hayes, Matthew R.;Skibicka, Karolina P.;Grill, Harvey J.
通讯作者：
Grill, Harvey J.