Schwob J E, Szumowski K E, Stasky A A
Department of Anatomy and Cell Biology, SUNY Health Science Center, Syracuse 13210.
J Neurosci. 1992 Oct;12(10):3896-919. doi: 10.1523/JNEUROSCI.12-10-03896.1992.
In most neural systems, developing neurons are trophically dependent on contact with their synaptic target for their survival and for some features of their differentiation. However, in the olfactory system, it is unclear whether or not the survival and differentiation of olfactory sensory neurons depend on contact with the olfactory bulb (normally the sole synaptic target for these neurons). In order to address this issue, we examined neuronal life-span and differentiation in adult rats subjected to unilateral olfactory bulb ablation at least 1 month prior to use. Life-span of a newly generated cohort of olfactory neurons was determined by labeling them at their "birth" via the incorporation of 3H-thymidine. In the absence of the bulb, neurons are continually produced at a twofold greater rate. However, the epithelium on the ablated side is thinner, indicating that average neuronal life-span must be reduced in the targetless epithelium. Indeed, nearly 90% of the labeled neurons disappear from the bulbectomized side between 5 d and 2 weeks of neuronal age. Moreover, on electron microscopic examination, olfactory axons are degenerating in large numbers on the ablated side. Since labeled neurons migrate apically through the width of the epithelium during this same period, it appears that most, if not all, neurons on the ablated side have a life-span on the order of 2 weeks or less. In contrast, there is a more moderate degree of neuronal loss on the unoperated side of the same animals during the first 2 weeks after tracer injection, and that occurs while the neurons are concentrated in the deeper half of the epithelium, suggesting that there is a preexisting population of neurons in the control epithelium that does not die during this period. Likewise, degenerating axons are much less frequent on the unoperated side. We conclude that life-span is significantly shorter for olfactory neurons born in the targetless epithelium and that olfactory neurons are trophically dependent on the presence of the bulb for their prolonged survival. Neuronal differentiation in the absence of the bulb was assessed according to ultrastructural criteria and the pattern of protein expression using antisera to the growth associated protein GAP-43 and the olfactory marker protein. By both measures, most neurons in the epithelium on the bulbectomized side, but not all, are immature.(ABSTRACT TRUNCATED AT 400 WORDS)
在大多数神经系统中，发育中的神经元在营养上依赖于与它们的突触靶点接触以维持生存并实现某些分化特征。然而，在嗅觉系统中，嗅觉感觉神经元的生存和分化是否依赖于与嗅球（通常是这些神经元唯一的突触靶点）的接触尚不清楚。为了解决这个问题，我们检查了至少在使用前1个月接受单侧嗅球切除的成年大鼠的神经元寿命和分化情况。通过在新生成的一群嗅觉神经元“诞生”时通过掺入3H-胸腺嘧啶对它们进行标记，来确定其寿命。在没有嗅球的情况下，神经元的产生速度持续快两倍。然而，切除侧的上皮更薄，这表明无靶点上皮中神经元的平均寿命必定缩短。实际上，在神经元年龄的5天至2周之间，近90% 的标记神经元从切除嗅球的一侧消失。此外，电子显微镜检查显示，切除侧大量嗅觉轴突正在退化。由于在此期间标记神经元从上皮宽度的基部向顶部迁移，看来切除侧的大多数（如果不是全部）神经元的寿命约为2周或更短。相比之下，在同一动物未手术侧，在注射示踪剂后的前2周内神经元损失程度较为适中，而且这种损失发生在神经元集中在上皮较深的一半时，这表明对照上皮中存在一群预先存在的神经元在此期间不会死亡。同样，未手术侧退化轴突的频率要低得多。我们得出结论，在无靶点上皮中诞生的嗅觉神经元寿命明显较短，并且嗅觉神经元在营养上依赖于嗅球的存在以实现其长期存活。根据超微结构标准以及使用针对生长相关蛋白GAP-43和嗅觉标记蛋白的抗血清的蛋白质表达模式，评估了无嗅球情况下的神经元分化。通过这两种测量方法，切除嗅球侧上皮中的大多数神经元（但不是全部）是不成熟的。（摘要截短至400字）
