Buckland M E, Cunningham A M
Sensory Neurobiology Group, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Ann N Y Acad Sci. 1998 Nov 30;855:260-5. doi: 10.1111/j.1749-6632.1998.tb10579.x.
Neurogenesis, axonal outgrowth and synapse formation are usually restricted to specific stages during central nervous system development, but the mature olfactory system maintains these capacities. The cycle of neuronal turnover can be experimentally induced by surgical ablation of the olfactory bulb (OB). We are interested in the growth factor regulation of these processes and the trophic role played by the target tissue, the OB. We studied the immunohistochemical expression of three neurotrophic factors, brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the rat olfactory neuroepithelium (ON) and OB and in target-deprived ON at 1, 3 and 12 weeks post unilateral bulbectomy. We found BDNF immunoreactivity (IR) was restricted to the basal cells and did not alter postbulbectomy. GDNF-IR was expressed by mature olfactory receptor neurons (ORNs), their axons and target cells in the OB in controls, but was absent from the ON postbulbectomy. Hence, the expression of GDNF by ORNs was found to be target-dependent. CNTF-IR was present in ORNs and their target cells in the OB, in basal cells and in some immature ORNs. Postbulbectomy, CNTF-IR was unaltered in the basal cells, and very low levels were detectable in maturing ORNs in the ON. Our results indicate that these three factors may contribute to the trophic regulation of this neuronal pathway in a coordinated fashion. Previous work has shown that BDNF promotes survival of ORNs in vitro, and TrkB expression has been found in both immature and mature ORNs. Hence, BDNF produced by basal cells may be acting locally on neurons expressing TrkB. Expression of CNTF by both the basal cells and the ORNs suggests that it may play an integral role in this neuronal differentiation pathway. Finally, the expression of GDNF exclusively by mature ORNs in the ON, its presence in the target cells in the OB and abolition of expression by bulbectomy, suggests that it may be target-derived. This provides a major mechanism by which the bulb could exert trophic influences on ORNs.
神经发生、轴突生长和突触形成通常局限于中枢神经系统发育的特定阶段，但成熟的嗅觉系统保留了这些能力。通过手术切除嗅球（OB）可实验性诱导神经元更替周期。我们对这些过程的生长因子调节以及靶组织OB所起的营养作用感兴趣。我们研究了三种神经营养因子，即脑源性神经营养因子（BDNF）、胶质细胞系源性神经营养因子（GDNF）和睫状神经营养因子（CNTF）在大鼠嗅觉神经上皮（ON）和OB以及单侧球切除术后1、3和12周靶剥夺ON中的免疫组化表达。我们发现BDNF免疫反应性（IR）局限于基底细胞，球切除术后无变化。在对照组中，GDNF-IR由成熟的嗅觉受体神经元（ORN）、其轴突和OB中的靶细胞表达，但球切除术后ON中不存在。因此，发现ORN对GDNF的表达是靶依赖性的。CNTF-IR存在于ORN及其在OB中的靶细胞、基底细胞和一些未成熟的ORN中。球切除术后，基底细胞中的CNTF-IR无变化，ON中成熟ORN中可检测到极低水平。我们的结果表明，这三种因子可能以协调的方式对该神经元通路的营养调节起作用。先前的研究表明，BDNF在体外促进ORN的存活，并且在未成熟和成熟的ORN中均发现了TrkB表达。因此，基底细胞产生的BDNF可能在局部作用于表达TrkB的神经元。基底细胞和ORN均表达CNTF表明它可能在该神经元分化途径中起不可或缺的作用。最后，GDNF仅由ON中的成熟ORN表达，其存在于OB中的靶细胞中且球切除后表达消失，表明它可能源自靶组织。这提供了球对ORN发挥营养影响的主要机制。
