Horton A R, Barlett P F, Pennica D, Davies A M
School of Biological and Medical Sciences, Bute Medical Buildings, University of St Andrews, Fife, Scotland.
Eur J Neurosci. 1998 Feb;10(2):673-9. doi: 10.1046/j.1460-9568.1998.00079.x.
To investigate when the neurotrophic cytokines ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin-M (OSM), interleukin-6 (IL-6) and cardiotrophin-1 (CT-1) act on developing sensory neurones and whether they co-operate with neurotrophins in regulating neuronal survival, we studied the in vitro trophic effects of these factors on two well-characterized populations of cranial sensory neurones at closely staged intervals throughout embryonic development. The cutaneous sensory neurones of the trigeminal ganglion, which show an early, transient survival response to BDNF and NT3 before becoming NGF-dependent, were supported by CNTF, LIF, OSM and CT-1 during the late fetal period, several days after the neurones become NGF-dependent. At this stage of development, these cytokines promoted the survival of a subset of NGF-responsive neurones. The enteroceptive neurones of the nodose ganglion, which retain dependence on BDNF throughout fetal development, were supported throughout their development by CNTF, LIF, OSM and CT-1, and displayed an additional survival response to IL-6 in the late fetal period. These findings indicate that populations of sensory neurones display different developmental patterns of cytokine responsiveness and show that embryonic trigeminal neurones pass through several phases of differing neurotrophic factor survival requirements.
为了研究神经营养细胞因子睫状神经营养因子(CNTF)、白血病抑制因子(LIF)、抑瘤素-M(OSM)、白细胞介素-6(IL-6)和心肌营养素-1(CT-1)何时作用于发育中的感觉神经元,以及它们在调节神经元存活方面是否与神经营养因子协同作用,我们在胚胎发育的各个紧密阶段,研究了这些因子对两个特征明确的颅神经感觉神经元群体的体外营养作用。三叉神经节的皮肤感觉神经元在对脑源性神经营养因子(BDNF)和神经营养因子-3(NT3)产生早期短暂的存活反应后,会转变为依赖神经生长因子(NGF),在胎儿后期,即神经元变得依赖NGF几天后,CNTF、LIF、OSM和CT-1对其起到支持作用。在这个发育阶段,这些细胞因子促进了一部分对NGF有反应的神经元的存活。结状神经节的内脏感觉神经元在整个胎儿发育过程中一直依赖BDNF,在其整个发育过程中都受到CNTF、LIF、OSM和CT-1的支持,并且在胎儿后期对IL-6表现出额外的存活反应。这些发现表明,感觉神经元群体表现出不同的细胞因子反应发育模式,并表明胚胎三叉神经元经历了几个不同神经营养因子存活需求的阶段。