Reduction of NT-3 or TrkC results in fewer putative vagal mechanoreceptors in the mouse esophagus
Reduction of NT-3 or TrkC results in fewer putative vagal mechanoreceptors in the mouse esophagus
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DOI：
10.1016/j.autneu.2003.08.003
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发表时间：
2003-10-31
影响因子：
2.7
通讯作者：
Neuhuber, WL
中科院分区：
文献类型：
--
作者：
Raab, M;Wörl, R;Neuhuber, WL
神经节内层流末梢（IGLE）代表整个胃肠道的主要迷走神经传入结构。形态学和功能数据都表明机械感觉的作用。IGLE数量显著改变的动物模型的可用性将有助于阐明它们在特定器官中的功能意义。本研究采用结状神经节顺行麦胚凝集素-辣根过氧化物酶示踪法（WGA-HRP）标记神经营养素-3（NT-3）或酪氨酸激酶C受体（TrkC）缺陷小鼠和对照组小鼠食管IGLE。这种方法仅在可存活的杂合突变体中可行。使用标准化方案在四甲基联苯胺（TMB）处理的全血中计数IGLE。肌间神经元的定量在铜蛋白蓝染色的标本中进行。在用甲酚紫染色的冷冻切片中进行结状神经元计数。食管中IGLE的数量在杂合NT-3（NT-3+/-）和杂合TrkC（TrkC+/-）突变体中均显著减少（分别减少65%和40%）。NT-3+/-小鼠的结状神经元数量也显著减少（减少48%），而TrkC+/-突变体的减少不显著（减少11%）。两种突变株的食管肌间神经元均未减少，IGLE的数量不足不太可能继发于肌间神经元的减少。虽然只有杂合突变体可以研究，这些结果表明，食管IGLE共享神经营养依赖NT-3/TrkC与脊髓本体感受器和一些皮肤mechanosensors。这与它们作为迷走神经机械传感器的功能一致，迷走神经机械传感器对反射性麻痹至关重要。(C)2003 Elsevier B. V.保留所有权利。
Intraganglionic laminar endings (IGLEs) represent major vagal afferent structures throughout the gastrointestinal tract. Both morphological and functional data suggested a mechanosensory role. Elucidation of their functional significance in a particular organ would be facilitated by the availability of animal models with significantly altered numbers of IGLEs. The present study was aimed at searching for mouse strains fulfilling this criterion in the esophagus.Anterograde wheat germ agglutinin-horseradish peroxidase tracing (WGA-HRP) from nodose ganglion was used in order to label esophageal IGLEs in mice deficient for neurotrophin-3 (NT-3) or tyrosine kinase C-receptor (TrkC) and in control littermates. This approach was feasible only in heterozygous mutants which are viable. IGLEs were counted in tetramethylbenzidine (TMB) processed wholemounts using a standardised protocol. Quantification of myenteric neurons was done in cuprolinic blue-stained specimens. Nodose neuron counts were performed in cryostat sections stained with cresyl violet. Numbers of IGLEs in the esophagus were significantly reduced in both heterozygous NT-3 (NT-3+/-) and heterozygous TrkC (TrkC+/-) mutants (65% and 40% reduction, respectively). Numbers of nodose neurons were also significantly reduced in NT-3+/- mice (48% reduction), while their reduction in TrkC+/- mutants was insignificant (11% reduction). There was no reduction of myenteric neurons in the esophagus of either mutant strain.The numeric deficiency of IGLEs was unlikely to be secondary to reduction of myenteric neurons. Although only heterozygous mutants could be studied, these results suggest that esophageal IGLEs share neurotrophin dependence on NT-3/TrkC with spinal proprioceptors and some cutaneous mechanosensors. This concurs with their proposed function as vagal mechanosensors crucial for reflex peristalsis. (C) 2003 Elsevier B.V. All rights reserved.