LOCALIZATION AND REGULATION OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR EXPRESSION IN THE RAT OLFACTORY SYSTEM DURING DEVELOPMENT AND REGENERATION
LOCALIZATION AND REGULATION OF LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR EXPRESSION IN THE RAT OLFACTORY SYSTEM DURING DEVELOPMENT AND REGENERATION
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DOI：
10.1002/cne.903440303
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发表时间：
1994-06-15
影响因子：
2.5
通讯作者：
SHIPLEY, MT
中科院分区：
文献类型：
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作者：
GONG, QZ;BAILEY, MS;SHIPLEY, MT
神经生长因子(NGF)是一种经典的神经营养因子，在周围神经系统和部分中枢神经系统中促进神经元的存活、维持、再生和分化。NGF活性是由细胞表面受体介导的，包括低亲和力NGF受体(LNGFr)，它由一些外周和中枢神经元表达，存在于发育和再生的外周神经雪旺细胞上。嗅觉系统是研究LNGFr在神经元发育和再生中作用的有用模型。嗅觉轴突进入大脑的生长始于胚胎，并持续到出生后的最初几周。在成熟动物中，嗅觉感受器神经元(ON)持续更新和生成，新的轴突不断生长进入嗅球。这些新的轴突沿着先前存在的嗅觉通路生长。在成熟的嗅觉系统中，已观察到LNGFr位于嗅球的肾小球层，嗅球是Orns的靶标。然而，LNGFr的细胞定位和发育表达尚不清楚。在这里，我们验证了LNGFr在嗅神经中的表达在发育中受到调节的假设，并在成熟的嗅神经损伤后重新诱导。LNGFr免疫反应(IR)首先在胚胎第13天的嗅黏膜和胚胎第14天的嗅神经中被观察到。LNGFr-IR在胚胎发育过程中在神经中表达增加，在出生后第5天左右开始下降，在正常成人中几乎检测不到。染色结果表明LNGFr位于嗅神经雪旺细胞上。成年嗅神经内有LNGFr-IR条带。我们推测，这些条纹可能代表了LNGFr的瞬时重新表达，与正常嗅觉神经元的更新和替换有关。与这一假说一致，LNGFr在嗅觉上皮损伤后的成年嗅神经中强健地重新表达。在发育后期(E21)和成年，LNGFr-IR也观察到在嗅球深层的纤维上。在基底前脑斜角带核(NDB)的神经元中也观察到LNGFr-IR。NDB是嗅球胆碱能传入的唯一来源。因此，我们通过损毁NDB验证了嗅球深层的LNGFr位于NDB轴突上的假设。损伤后，LNGFr-IR在嗅球深层消失，但仍留在肾小球层。我们得出结论，LNGFr-IR与嗅觉系统中几个不同的细胞群有关。这表明LNGFr-IR在嗅觉系统中发挥着多种不同的功能，包括支持嗅球轴突的生长和再生，以及维持嗅球的胆碱能神经支配。(C)1994年Wiley-Liss，Inc.
Nerve growth factor (NGF), a classic neurotrophic factor, promotes neuronal survival, maintenance, regeneration and differentiation in the peripheral nervous system and parts of the central nervous system. NGF activity is mediated by cell surface bound receptors including the low affinity NGF receptor (LNGFr) which is expressed by some peripheral and central neurons and is present on peripheral nerve Schwann cells during development and regeneration.The olfactory system is a useful model for the study of the role of LNGFr in neuronal development and regeneration. The growth of olfactory axons into the brain begins in the embryo and continues through the first few postnatal weeks. In mature animals there is persistent turnover and generation of olfactory receptor neurons (ORNs) and continuous growth of new axons into the olfactory bulb. These new axons grow along the preexisting olfactory pathway. In the mature olfactory system, LNGFr has been observed in the glomerular layer of the olfactory bulb, the target of ORNs. However, neither the cellular localization nor the developmental expression of LNGFr has been characterized. Here, we tested the hypothesis that LNGFr expression is developmentally regulated in the olfactory nerve and is reinduced following injury to the mature olfactory nerve.LNGFr-immunoreactivity (IR) was first observed in the olfactory mucosa at embryonic day (E)13 and in the olfactory nerve at E14. LNGFr-IR increased in the nerve during embryonic development, began to decrease at around postnatal day (P)5 and was scarcely detectable in normal adults. The staining pattern suggests that LNGFr is located on the olfactory nerve Schwann cells. Streaks of LNGFr-IR were present in the adult olfactory nerve. We reasoned that these streaks might represent transient reexpression of LNGFr associated with normal olfactory neuron turnover and replacement. Consistent with this hypothesis, LNGFr was robustly reexpressed in the adult olfactory nerve following lesion of the olfactory epithelium.Starting late in development (E21) and in the adult, LNGFr-IR was also observed on fibers in deep layers of the olfactory bulb. LNGFr-IR was also observed in neurons of the nucleus of the diagonal band (NDB) in the basal forebrain. NDB is the sole source of cholinergic afferents of the olfactory bulb. Thus, we tested the hypothesis that LNGFr in the deep layers of the olfactory bulb is located on NDB axons by making lesions of NDB. Following the lesion, LNGFr-IR disappeared in the deep layers of the olfactory bulb but remained in the glomerular layer.We conclude that LNGFr-IR is associated with several distinct populations of cells in the olfactory system. This suggests that LNGFr-IR plays several distinct functional roles in the olfactory system, including support of olfactory axon growth and regeneration and maintenance of cholinergic innervation of the olfactory bulb. (C) 1994 Wiley-Liss, Inc.