Regulation of NGF-family ligands and receptors in adulthood and senescence: correlation to degenerative and regenerative changes in cutaneous innervation
Regulation of NGF-family ligands and receptors in adulthood and senescence: correlation to degenerative and regenerative changes in cutaneous innervation
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DOI：
10.1046/j.1460-9568.2000.00149.x
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发表时间：
2000-08-01
影响因子：
3.4
通讯作者：
Fundin, BT
中科院分区：
文献类型：
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作者：
Bergman, E;Ulfhake, B;Fundin, BT
据报道，在发育过程中，胡须毛囊中各种类型的神经末梢对神经营养素的依赖性高度不同。这些依赖在多大程度上延伸并在成年过程中发挥作用，在很大程度上还没有解决。在这里，我们使用原位杂交和免疫组织化学方法显示，神经营养因子和trk/p75受体的表达在成年期持续存在。根据其表达谱，许多类别的皮肤神经末梢揭示了成年动物在发育过程中类似的配体-受体依赖关系，而其他种群似乎改变了它们的依赖关系。此外，我们的数据表明，由于机械磨损而具有高周转率的感觉末端，例如位于环窦水平的Merkel细胞-轴突复合体，比具有较少易损性位置的末端，例如网脊领处的Merkel细胞-轴突复合体，显示出更复杂的配体-受体表达表型。因此，神经营养因子-3(NT3)/TrkA信号通路对成年后Merkel细胞-轴突复合体在环窦水平的持续终末可塑性可能起重要作用。支持神经营养因子信号在维持成人皮肤神经支配中的作用的证据还来自配体受体表达改变(S)与衰老过程中轴突/终末异常之间的密切相关性。因此，随着年龄的增长，靶神经营养因子的表达减少，尤其是NT3和NT4，导致特定部位的感觉终末丢失，伴随着再生/萌发轴突进入新靶区的异常生长。皮肤神经的老化，表现为退行性和再生性事件，似乎与感觉神经元和靶组织之间的神经营养相互作用的变化密切相关。
During development, a highly differential neurotrophin dependency is reported for various types of nerve endings in the whisker follicle. To what extent these dependencies extend and play a role in adulthood is largely unresolved. We show here, using in situ hybridization and immunohistochemistry that the expression of neurotrophins and trk/p75 receptors persists in adulthood. As suggested by their expression profiles, many classes of cutaneous nerve endings disclose similar ligand-receptor dependencies in adult animals as during development, while other populations appear to switch their dependency. Furthermore, our data suggest that sensory endings that have a high turnover due to mechanical wear and tear, e.g. Merkel cell-neurite complexes at the level of ring sinus show a more complex ligand-receptor expression phenotype than do endings with a less vulnerable location, e.g. the Merkel cell-neurite complexes at the rete ridge collar. Thus, neurotrophin-3 (NT3)/trkA signalling is suggested to be important for a continuous terminal plasticity of Merkel cell-neurite complexes at the level of ring sinus in adulthood. Evidence supporting a role for neurotrophin signalling in maintaining the adult cutaneous innervation also comes from the close correlation between altered ligand-receptor expression(s) and axonal/terminal aberrations in senescence. Thus, an ageing-related decrease in target neurotrophin expression, notably NT3 and NT4, results in a site-specific loss of sensory terminals concomitant with an aberrant growth of regenerating/sprouting axons into new target fields. Ageing of the cutaneous innervation, manifested in degenerative and regenerative events, seems strongly associated with changes in neurotrophic interactions between sensory neurons and target tissues.