The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes
The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes
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DOI：
10.1523/jneurosci.5018-10.2011
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发表时间：
2011-06-22
影响因子：
5.3
通讯作者：
von Bartheld, Christopher S.
中科院分区：
文献类型：
--
作者：
Feng, Cheng-Yuan;Wiggins, Larisa M.;von Bartheld, Christopher S.
神经元可以通过两种主要途径获得信号分子：突触传递（“布线传递”）和非突触传递（“体积传递”）。布线传输通常被认为是更重要的神经元信号传导模式。使用胚胎鸡蓝斑（LoC）作为模型，我们量化和比较神经营养因子神经生长因子（NGF）的传递途径，无论是通过多突触轴突通路或通过CSF。我们现在表明，轴突通路从眼睛到LoC涉及轴突轴突传递的神经生长因子与受体转换（p75到trkA）在视顶盖。除了轴突途径，鸡胚的LoC通过一种专门的胶质细胞/室管膜细胞类型（延伸细胞）特权进入CSF。禽类LoC以高度特异性的方式从CSF内化NGF和激素尾加压素（促肾上腺皮质激素释放因子家族配体）。超微结构水平的定量放射自显影显示，伸长细胞transcytose和提供神经生长因子的LoC神经元通过突触接触。LoC相关的伸长细胞表达p75和trkA受体。从CSF中提取的NGF对LoC神经元具有生理作用，如在功能获得和功能丧失实验中显著改变的核直径所证明的。定量的神经生长因子提取表明，与多突触轴突的神经生长因子运输到LoC的路线相比，伸长细胞的路线是显着更有效的。我们的结论是，一些临床上重要的神经元群体，如LoC可以使用一个高效的“后门”接口的CSF，并可以通过这种tanycyte控制的途径接收信号。
Neurons can access signaling molecules through two principal pathways: synaptic transmission ("wiring transmission") and nonsynaptic transmission ("volume transmission"). Wiring transmission is usually considered the far more important mode of neuronal signaling. Using embryonic chick locus ceruleus (LoC) as a model, we quantified and compared routes of delivery of the neurotrophin nerve growth factor (NGF), either through a multisynaptic axonal pathway or via the CSF. We now show that the axonal pathway from the eye to the LoC involves axo-axonic transfer of NGF with receptor switching (p75 to trkA) in the optic tectum. In addition to the axonal pathway, the LoC of chick embryos has privileged access to the CSF through a specialized glial/ependymal cell type, the tanycyte. The avian LoC internalizes from the CSF in a highly specific fashion both NGF and the hormone urotensin (corticotropin-releasing factor family ligand). Quantitative autoradiography at the ultrastructural level shows that tanycytes transcytose and deliver NGF to LoC neurons via synaptoid contacts. The LoC-associated tanycytes express both p75 and trkA receptors. The NGF extracted by tanycytes from the CSF has physiological effects on LoC neurons, as evidenced by significantly altered nuclear diameters in both gain-of-function and loss-of-function experiments. Quantification of NGF extraction shows that, compared with multisynaptic axonal routes of NGF trafficking to LoC, the tanycyte route is significantly more effective. We conclude that some clinically important neuronal populations such as the LoC can use a highly efficient "back door" interface to the CSF and can receive signals via this tanycyte-controlled pathway.