APOPTOSIS IN THE NEURONAL LINEAGE OF THE MOUSE OLFACTORY EPITHELIUM - REGULATION IN-VIVO AND IN-VITRO
APOPTOSIS IN THE NEURONAL LINEAGE OF THE MOUSE OLFACTORY EPITHELIUM - REGULATION IN-VIVO AND IN-VITRO
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DOI：
10.1006/dbio.1995.0025
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发表时间：
1995-11-01
影响因子：
2.7
通讯作者：
CALOF, AL
中科院分区：
文献类型：
--
作者：
HOLCOMB, JD;MUMM, JS;CALOF, AL
小鼠的嗅觉上皮 (OE) 提供了一个独特的系统，用于了解细胞诞生和细胞死亡如何相互作用以调节发育和再生过程中的神经元数量。我们检查了正常成年小鼠 OE 中的细胞死亡情况；在接受单侧嗅球切除术的成年小鼠中（手术切除一个嗅球，即 OE 嗅觉受体神经元（ORN）的突触目标）；以及源自小鼠胚胎 OE 的原代细胞培养物。在体内，神经元谱系各个阶段的细胞——增殖的神经元前体、未成熟的ORN和成熟的ORN——都表现出细胞凋亡的死亡迹象；非神经元细胞没有。球茎切除术显着增加了球茎切除侧 OE 中凋亡细胞的数量。球茎切除术后不久，所有阶段的神经元细胞死亡增加。后来，细胞死亡持续升高，但这是由于成熟 ORN 单独导致细胞凋亡增加。在体外，ORN 及其前体的凋亡性死亡可以通过防止其他细胞凋亡的药物来抑制：金精三羧酸 (ATA)、环 AMP 的膜渗透类似物 (CPT-cAMP) 以及生长因子神经营养蛋白家族的某些成员（脑源性神经营养因子、神经营养蛋白 3 和神经营养蛋白 3）。 神经营养因子 5)，尽管没有任何神经营养因子能像 ATA 或 CPT-cAMP 那样有效地促进生存。与观察到的神经营养蛋白的作用一致，免疫组织化学将神经营养蛋白受体 trkB 和 trkC 定位于分散在新生儿 OE 中的 ORN 部分。这些结果表明，细胞凋亡可能在神经元谱系的多个阶段调节 OE 中的神经元数量，并且多种因素（可能包括某些神经营养素）可能参与此过程。 (C) 1995 学术出版社
The olfactory epithelium (OE) of the mouse provides a unique system for understanding how cell birth and cell death interact to regulate neuron number during development and regeneration. We have examined cell death in the OE in normal adult mice; in adult mice subjected to unilateral olfactory bulbectomy (surgical removal of one olfactory bulb, the synaptic target of olfactory receptor neurons (ORNs) of the OE); and in primary cell cultures derived from embryonic mouse OE. In vivo, cells at all stages in the neuronal lineage-proliferating neuronal precursors, immature ORNs, and mature ORNs-displayed signs of apoptotic cell death; nonneuronal cells did not. Bulbectomy dramatically increased the number of apoptotic cells in the OE on the bulbectomized side. Shortly following bulbectomy, increased cell death involved neuronal cells of all stages. Later, cell death remained persistently elevated, but this was due to increased apoptosis by mature ORNs alone. In vitro, apoptotic death of both ORNs and their precursors could be inhibited by agents that prevent apoptosis in other cells: aurintricarboxylic acid (ATA), a membrane-permeant analog of cyclic AMP (CPT-cAMP), and certain members of the neurotrophin family of growth factors (brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 5), although no neurotrophin was as effective at promoting survival as ATA or CPT-cAMP. Consistent with observed effects of neurotrophins, immunohistochemistry localized the neurotrophin receptors trkB and trkC to fractions of ORNs scattered throughout neonatal OE. These results suggest that apoptosis may regulate neuronal number in the OE at multiple stages in the neuronal lineage and that multiple factors-potentially including certain neurotrophins-may be involved in this process. (C) 1995 Academic Press, Inc.