Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium.

Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium.
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DOI:
10.1016/j.neuroscience.2009.06.040
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发表时间:
2009-09-29
期刊:
影响因子:
3.3
通讯作者:
Hegg, C. C.
Hegg, C. C.
中科院分区:
医学3区
文献类型:
--
作者:
Jia, C.;Doherty, J. P.;Crudgington, S.;Hegg, C. C.

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在中枢神经系统中,ATP 诱导神经营养因子的合成和释放、细胞增殖和分化。嗅觉系统是多能祖细胞在一生中持续增殖并分化为神经元的部位之一。我们通过测量 5-溴-2-脱氧尿苷掺入来检验 ATP 启动嗅觉上皮细胞增殖的假设。在鼻腔滴注 ATP、UTP、ATPγS 或盐水(0 小时)前 30 分钟,用盐水或嘌呤能受体拮抗剂(吡哆醛-磷酸-6-偶氮苯基-2',4'-二磺酸盐 + 苏拉明)对成年小鼠进行腹膜内或鼻内预处理。小鼠在 42-46 小时内接受 3 次 5-溴-2-脱氧尿苷注射,并在 ATP 滴注后 2、9 或 16 天处死。在用盐水预处理的组中,与鼻内盐水对照相比,ATP、UTP或ATPγS显着增加了5-溴-2-脱氧尿苷掺入。在用嘌呤能受体拮抗剂预处理的组中,盐水、ATP、UTP或ATPγS滴注并没有显着增加5-溴-2-脱氧尿苷的掺入。在新生儿和培养切片制剂中观察到类似的结果。鼻内滴注 ATP 还增加了成人增殖细胞核抗原的蛋白质水平。用嘌呤能受体拮抗剂预处理抑制了 ATP 诱导的增殖细胞核抗原的增加。在成人中,掺入 5-溴-2-脱氧尿苷的细胞子集分别在第 2、9 和 16 天时对神经元标记物 MASH 1、GAP43 和 OMP 产生免疫反应。总的来说,这些数据表明嘌呤能受体激活诱导小鼠嗅上皮细胞的增殖和神经元分化。我们认为损伤时释放的细胞外 ATP 可以诱导增殖并促进嗅上皮的神经再生。
In the CNS, ATP induces the synthesis and release of neurotrophic factors, cell proliferation, and differentiation. The olfactory system is one site where multipotent progenitor cells continue to proliferate and differentiate into neurons throughout life. We tested the hypothesis that ATP initiates proliferation in olfactory epithelium by measuring 5-bromo-2-deoxyuridine incorporation. Adult mice were pre-treated intraperitoneally or intranasally with saline or purinergic receptor antagonists (pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate + suramin) 30 min prior to nasal instillation of ATP, UTP, ATPγS or saline (0 hr). Mice received three injections of 5-bromo-2-deoxyuridine between 42–46 hr, and were sacrificed at 2, 9 or 16 days post ATP instillation. ATP, UTP or ATPγS significantly increased 5-bromo-2-deoxyuridine incorporation compared to intranasal saline controls in groups pre-treated with saline. Saline, ATP, UTP or ATPγS instillation did not significantly increase 5-bromo-2-deoxyuridine incorporation in groups pre-treated with purinergic receptor antagonists. Similar results were observed in neonates and in a cultured slice preparation. Intranasal instillation of ATP also increased the protein levels of proliferating cell nuclear antigen in adults. Pre-treatment with purinergic receptor antagonists inhibited the ATP-induced increase in proliferating cell nuclear antigen. In adults, a subset of the cells that incorporated 5-bromo-2-deoxyuridine were immunoreactive to neuronal markers MASH 1, GAP43, and OMP at 2, 9, and 16 days, respectively. Collectively, these data indicate that purinergic receptor activation induces proliferation and neuronal differentiation in the mouse olfactory epithelium. We propose that extracellular ATP released upon injury could induce proliferation and promote the neuroregeneration of the olfactory epithelium.
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DOI: 10.1016/0306-9877(92)90190-n
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期刊: MEDICAL HYPOTHESES
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