Role of nitric oxide in subventricular zone neurogenesis

Role of nitric oxide in subventricular zone neurogenesis
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DOI:
10.1016/j.brainresrev.2005.01.001
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发表时间:
2005-09-01
影响因子:
--
通讯作者:
Estrada, C
Estrada, C
中科院分区:
其他
文献类型:
--
作者:
Matarredona, ER;Murillo-Carretero, M;Estrada, C

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根据解剖学发现,室下区 (SVZ) 神经母细胞位于 NO 产生细胞附近,并且 NO 在许多细胞类型中具有已知的抗增殖作用,有人提出一氧化氮 (NO) 在成人神经发生中的可能作用。已经在啮齿类动物中进行了全身和脑室内注射 NO 合酶 (NOS) 抑制剂 L-NAME 的实验。 NOS 抑制导致 SVZ 和嗅球 (OB) 中增殖细胞数量显着增加。 NO 优先对表达巢蛋白但不表达 β III-微管蛋白的细胞群发挥其细胞抑制作用,这可能对应于 SVZ 中描述的 C 型细胞。 NO 对 SVZ 细胞增殖的负面影响也在 SVZ 原代培养物中得到证实。表皮生长因子受体 (EGFR) 酪氨酸激酶活性的抑制被描述为 NO 在 SVZ 细胞中抗增殖作用的分子机制之一。使用内源表达 EGFR 的神经母细胞瘤细胞系 NB69 获得了支持这一结论的生化数据。在这些细胞中,NO 的抗有丝分裂作用发生在抑制 EGFR 酪氨酸磷酸化时,可能是通过受体的直接 S-亚硝基化。最新发表的关于 NO 和神经发生的报告表明,NO 通过调节 SVZ 祖细胞的增殖和命运,在生理上参与成体神经发生的控制。这些效应可能部分归因于 S-亚硝基化对 EGFR 的直接抑制。 (c) 2005 Elsevier B.V. 保留所有权利。
A possible role of nitric oxide (NO) in adult neurogenesis has been suggested based on anatomical findings showing that subventricular zone (SVZ) neuroblasts are located close to NO-producing cells, and on the known antiproliferative actions of NO in many cell types.Experiments have been performed in rodents with systemic and intracerebroventricular administrations of the NO synthase (NOS) inhibitor L-NAME. NOS inhibition leads to significant increases in the number of proliferating cells in the SVZ and olfactory bulb (OB). NO exerts its cytostatic action preferentially on the cell population expressing nestin but not beta III-tubulin, which may correspond to the type C cells described in the SVZ. The negative effect of NO on SVZ cell proliferation has also been confirmed in SVZ primary cultures.An inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is described as one of the molecular mechanisms responsible for the antiproliferative, effect of NO in SVZ cells. Biochemical data supporting this conclusion has been obtained using the neuroblastoma cell line NB69, which endogenously expresses the EGFR. In these cells, the antimitotic action of NO occurs upon inhibition of the EGFR tyrosine phosphorylation, probably by a direct S-nitrosylation of the receptor.The latest published reports on NO and neurogenesis indicate that NO physiologically participates in the control of adult neurogenesis by modulating the proliferation and fate of the SVZ progenitor cells. These effects might be partially due to a direct inhibition of the EGFR by S-nitrosylation. (c) 2005 Elsevier B.V. All rights reserved.