Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Behavioral Neurogenetics Laboratory, Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Auton Neurosci. 2021 Jul;233:102811. doi: 10.1016/j.autneu.2021.102811. Epub 2021 Apr 19.
Vagal afferents form the primary gut-to-brain neural axis, communicating signals that regulate gastrointestinal (GI) function and promote satiation, appetition and reward. Neurotrophin-4 (NT-4) is essential for the survival of vagal smooth muscle afferents of the small intestine, but not the stomach. Here we took advantage of near-complete labeling of GI vagal mucosal afferents in Nav1.8cre-Rosa26tdTomato transgenic mice to determine whether these afferents depend on NT-4 for survival. We quantified the density and distribution of vagal afferent terminals in the stomach and small intestine mucosa and their central terminals in the solitary tract nucleus (NTS) and area postrema in NT-4 knockout (KO) and control mice. NT-4KO mice exhibited a 75% reduction in vagal afferent terminals in proximal duodenal villi and a 55% decrease in the distal ileum, whereas, those in the stomach glands remained intact. Vagal crypt afferents were also reduced in some regions of the small intestine, but to a lesser degree. Surprisingly, NT-4KO mice exhibited an increase in labeled terminals in the medial NTS. These findings, combined with previous results, suggest NT-4 is essential for survival of a large proportion of all classes of vagal afferents that innervate the small intestine, but not those that supply the stomach. Thus, NT-4KO mice could be valuable for distinguishing gastric and intestinal vagal afferent regulation of GI function and feeding. The apparent plasticity of central vagal afferent terminals - an increase in their density - could have compensated for loss of peripheral terminals by maintaining near-normal levels of satiety signaling.
迷走传入神经构成了主要的肠-脑神经轴，传递调节胃肠道 (GI) 功能和促进饱腹感、食欲和奖励的信号。神经生长因子-4 (NT-4) 对于小肠迷走平滑肌传入神经的存活是必不可少的，但对于胃则不是。在这里，我们利用 Nav1.8cre-Rosa26tdTomato 转基因小鼠中几乎完全标记的 GI 迷走黏膜传入神经，来确定这些传入神经是否依赖于 NT-4 来存活。我们定量了 NT-4 敲除 (KO) 和对照小鼠胃和小肠黏膜中的迷走传入神经末梢及其在孤束核 (NTS) 和最后区的中枢末端的密度和分布。NT-4KO 小鼠在近端十二指肠绒毛中的迷走传入神经末梢减少了 75%，在远端回肠中的减少了 55%，而胃腺中的迷走传入神经末梢则保持完整。迷走隐窝传入神经在小肠的一些区域也减少了，但程度较小。令人惊讶的是，NT-4KO 小鼠的中 NTS 中的标记末端增加了。这些发现，结合以前的结果，表明 NT-4 对于支配小肠的所有类型迷走传入神经的大部分存活是必不可少的，但对于供应胃的迷走传入神经则不是。因此，NT-4KO 小鼠可能对于区分胃和肠道迷走传入神经对 GI 功能和进食的调节非常有价值。中枢迷走传入神经末梢的明显可塑性——其密度增加——可能通过维持接近正常的饱腹感信号水平来补偿外周末梢的丧失。
