NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium.

NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium.
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DOI:
10.1016/j.nbd.2010.02.013
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发表时间:
2010-06
影响因子:
6.1
通讯作者:
Hegg CC
Hegg CC
中科院分区:
医学1区
文献类型:
--
作者:
Jia C;Hegg CC

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在CNS中,ATP在损伤时释放并通过嘌呤能受体促进神经增殖。在嗅上皮中,ATP促进新生小鼠神经营养因子NPY的合成和释放,并诱导新生小鼠和成年小鼠的神经增殖。我们测试的假设,NPY参与ATP诱导的神经增殖在成年小鼠嗅上皮。鼻内滴注ATP显著增加蛋白水平和NPY+细胞数量。鼻内滴注嘌呤能受体拮抗剂PPADS可显著降低ATP诱导的NPY上调。在ATP滴注后鼻内滴注NPY-Y1受体拮抗剂BIBP 3226显著抑制ATP诱导的BrdU掺入增加,表明在ATP滴注后释放NPY并激活Y1受体以促进神经增殖。这些数据表明,ATP通过上调NPY,释放NPY,和Y1受体激活启动神经增殖,并表明嗅上皮是很好的模型,研究在中枢神经系统的神经再生机制。
In the CNS, ATP is released upon injury and promotes neuroproliferation via purinergic receptors. In the olfactory epithelium, ATP promotes the synthesis and release of neurotrophic factor NPY in neonates and induces neuroproliferation in neonatal and adult mice. We tested the hypothesis that NPY is involved in ATP-induced neuroproliferation in adult mice olfactory epithelium. Intranasal instillation of ATP significantly increased protein levels and number of NPY+ cells. Pre-intranasal instillation of purinergic receptor antagonist PPADS significantly reduced ATP-induced upregulation of NPY. Intranasal instillation of NPY-Y1 receptor antagonist BIBP3226 following ATP instillation significantly inhibited the ATP-induced increase in BrdU incorporation, suggesting that NPY is released after ATP instillation and activates Y1 receptors to promote neuroproliferation. These data indicate that ATP initiates neuroproliferation via NPY upregulation, NPY release, and Y1 receptor activation, and suggests that the olfactory epithelium is good model to study neuroregenerative mechanisms in the CNS.
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