Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia.

Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia.
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DOI:
10.1002/cne.22645
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发表时间:
2011-09-01
影响因子:
2.5
通讯作者:
Basbaum, Allan I.
Basbaum, Allan I.
中科院分区:
医学3区
文献类型:
--
作者:
Braz, Joao M.;Ackerman, Larry;Basbaum, Allan I.

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我们最近开发了一种遗传transneuronal追踪方法,可以研究神经损伤改变的电路。我们产生了转基因(ZW-X)小鼠,其中表达的transneuronal示踪剂,麦胚凝集素(WGA),诱导在初级感觉神经元,但只有在切断其外周轴突。通过跟踪示踪剂跨神经元转运进入中枢神经系统(CNS),我们可以标记表达WGA的受损神经元参与的回路。在这里,我们使用ZW-X小鼠系来分析背根神经节(DRG)的神经节内损伤的感觉神经元和它们的相邻的“完整”的神经元之间的连接。由于神经肽Y(NPY)的表达强烈诱导后,DRG神经元外周轴突切断,我们交叉ZW-X小鼠线与小鼠表达Cre重组酶的影响下,NPY启动子。正如预期的那样,坐骨神经横断触发了NPY阳性DRG神经元中的WGA表达,其中大多数是大直径的。正如预期的那样,ATF-3的双标记,一种轴突受损的细胞体的标记物,显示示踪剂在受损的(即,轴突切断的)神经元。然而,我们也发现了未受伤的感觉神经元的DRG细胞体中的WGA示踪剂。重要的是,在没有神经损伤的情况下,没有WGA的神经节内转移。我们的研究结果表明,神经节内,细胞与细胞的通信,通过大分子的转移,发生在受损和邻近的未受伤的初级传入神经元的细胞体之间。
We recently developed a genetic transneuronal tracing approach that allows for the study of circuits that are altered by nerve injury. We generated transgenic (ZW-X) mice in which expression of a transneuronal tracer, wheat germ agglutinin (WGA), is induced in primary sensory neurons, but only after transection of their peripheral axon. By following the transneuronal transport of the tracer into the central nervous system (CNS) we can label the circuits that are engaged by the WGA-expressing damaged neurons. Here we used the ZW-X mouse line to analyze dorsal root ganglia (DRG) for intraganglionic connections between injured sensory neurons and their neighboring “intact” neurons. Because neuropeptide Y (NPY) expression is strongly induced in DRG neurons after peripheral axotomy, we crossed the ZW-X mouse line with a mouse that expresses Cre recombinase under the influence of the NPY promoter. As expected, sciatic nerve transection triggered WGA expression in NPY-positive DRG neurons, most of which are of large diameter. As expected, double labeling for ATF-3, a marker of cell bodies with damaged axons, showed that the tracer predominated in injured (i.e., axotomized) neurons. However, we also found the WGA tracer in DRG cell bodies of uninjured sensory neurons. Importantly, in the absence of nerve injury there was no intraganglionic transfer of WGA. Our results demonstrate that intraganglionic, cell-to-cell communication, via transfer of large molecules, occurs between the cell bodies of injured and neighboring noninjured primary afferent neurons.
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发表时间: 2003-03-01
影响因子: 2.5
作者:
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期刊: PAIN
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