Long-term survival of olfactory sensory neurons after target depletion.

Long-term survival of olfactory sensory neurons after target depletion.
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目标耗尽后嗅觉感觉神经元的长期存活。

DOI:
10.1002/cne.22084
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发表时间:
2009
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Guthrie,KathleenM
Guthrie,KathleenM
中科院分区:
--
文献类型:
--
作者:
Sultan-Styne,Krista;Toledo,Rafael;Walker,Christine;Kallkopf,Anna;Ribak,CharlesE;Guthrie,KathleenM

文献摘要

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成年嗅上皮和嗅球内神经元的终身添加和消除允许对感觉体验、学习和损伤后恢复的适应性结构反应。这两种结构的相互依赖性突出了被剥夺灯泡接触的感觉神经元的寿命缩短,并促使了灯泡的营养线索有助于其生存的假设。这些信号的具体身份和来源仍然未知。为了研究靶神经元在这种支持中的潜在作用,我们采用了神经毒性损伤来选择性地去除它们,同时保留剩余的神经投射通路,并检查了感觉神经元增殖和存活的动力学。用溴脱氧尿苷对祖细胞进行脉冲标记表明,与手术切除球一样,上皮细胞凋亡的增加在靶细胞的化学耗竭后触发了新神经元的加速产生。这些神经元的一个大的亚群没有经历过早死亡,而是长期存活。增加的增殖和延长的存活期的组合导致基本上正常数量的新感觉神经元存活长达5周,伴随嗅觉标记蛋白表达的恢复。通过定量聚合酶链反应(Q-PCR)测量的神经营养因子表达水平的变化,以及在损伤的球中观察到球细胞群的变化,包括在室管膜下区产生的新神经元的增加。这些数据表明,嗅觉感觉神经元可以通过从剩余或替代细胞来源获得足够的支持来适应其正常靶区的减少,以存活并维持其投射。J. Comp.神经元515:696-710,2009.© 2009 Wiley利斯公司
Life‐long addition and elimination of neurons within the adult olfactory epithelium and olfactory bulb allows for adaptive structural responses to sensory experience, learning, and recovery after injury. The interdependence of the two structures is highlighted by the shortened life span of sensory neurons deprived of bulb contact, and has prompted the hypothesis that trophic cues from the bulb contribute to their survival. The specific identity and source of these signals remain unknown. To investigate the potential role of target neurons in this support, we employed a neurotoxic lesion to selectively remove them while preserving the remaining nerve projection pathway, and examined the dynamics of sensory neuron proliferation and survival. Pulse‐labeling of progenitors with bromodeoxyuridine showed that, as with surgical bulb removal, increased apoptosis in the epithelium triggered accelerated production of new neurons after chemical depletion of target cells. Rather than undergoing premature death, a large subpopulation of these neurons survived long term. The combination of increased proliferation and extended survival resulted in essentially normal numbers of new sensory neurons surviving for as long as 5 weeks, with an accompanying restoration of olfactory marker protein expression. Changes in neurotrophic factor expression levels as measured by quantitative polymerase chain reaction (Q‐PCR), and in bulb cell populations, including the addition of new neurons generated in the subventricular zone, were observed in the injured bulb. These data indicate that olfactory sensory neurons can adapt to reductions in their normal target field by obtaining sufficient support from remaining or alternative cell sources to survive and maintain their projections. J. Comp. Neurol. 515:696–710, 2009. © 2009 Wiley‐Liss, Inc.