Stucky C L, DeChiara T, Lindsay R M, Yancopoulos G D, Koltzenburg M
Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
J Neurosci. 1998 Sep 1;18(17):7040-6. doi: 10.1523/JNEUROSCI.18-17-07040.1998.
Neurotrophin-4 (NT4) is the most recently discovered neurotrophic factor in mammals and, functionally, the least well understood. Here, we used mice that lack NT4 to determine whether NT4 is required for the survival of functionally identified subclasses of cutaneous sensory neurons. By using three independent methods of histological and electrophysiological analysis, we show that NT4 is specifically required for the survival of down hair (D-hair) receptors that innervate a subpopulation of hair follicles. All other functionally distinct types of afferents neurons innervating hairy skin were not affected in their survival or in their function. Previous studies have shown that BDNF is required for the mechanical sensitivity of slowly adapting (SA) mechanoreceptors but not for the postnatal survival of myelinated cutaneous afferent fibers. In contrast, the receptive properties of SA mechanoreceptors were not impaired in animals lacking NT4. Consequently, these data show that the two trkB ligands, NT4 and BDNF, have distinct and nonoverlapping roles in supporting cutaneous sensory neurons. Whereas NT4 is required for the survival of D-hair receptors, BDNF supports the mechanical function of SA fibers.
神经营养因子4（NT4）是哺乳动物中最近发现的神经营养因子，在功能方面，人们对其了解最少。在此，我们使用缺乏NT4的小鼠来确定功能性确定的皮肤感觉神经元亚类的存活是否需要NT4。通过使用三种独立的组织学和电生理分析方法，我们表明NT4是支配毛囊亚群的下毛（D毛）感受器存活所特需的。支配多毛皮肤的所有其他功能不同类型的传入神经元的存活或功能均未受到影响。先前的研究表明，BDNF是慢适应性（SA）机械感受器的机械敏感性所必需的，但不是有髓皮肤传入纤维出生后存活所必需的。相比之下，缺乏NT4的动物中SA机械感受器的感受特性并未受损。因此，这些数据表明，两种trkB配体NT4和BDNF在支持皮肤感觉神经元方面具有不同且不重叠的作用。NT4是D毛感受器存活所必需的，而BDNF则支持SA纤维的机械功能。
