Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone
Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone
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DOI：
10.1016/j.brainres.2003.10.010
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发表时间：
2004-01-09
期刊：
影响因子：
2.9
通讯作者：
Estrada, C
中科院分区：
文献类型：
--
作者：
Matarredona, ER;Murillo-Carretero, M;Estrada, C
啮齿类动物的脑室下区(SVZ)在动物的整个生命过程中保持着产生新神经元的能力。SVZ的神经前体细胞在存在表皮生长因子(EGF)的情况下在体外存活和增殖。一氧化氮(NO)已被证明参与发育过程中神经组织的形成，并具有抗增殖作用，部分是通过抑制EGF受体介导的。基于这些发现，我们研究了内源性产生的和内源性添加的NO对SVZ细胞增殖和分化的可能影响。取出生后小鼠SVZ的外植体，在含有EGF的条件下培养。用溴脱氧尿嘧啶核苷(BrdU)掺入法检测细胞从外植体中迁移出来并在培养中增殖。在体外培养72 h后，外植体周围形成的集落由神经元或神经胶质细胞以及未分化的祖细胞组成。在有长精索静脉曲张突起的神经细胞中，观察到神经元型一氧化氮合酶的免疫反应。一氧化氮合酶抑制剂L精氨酸甲酯(L-NAME)可使BrdU免疫反应阳性细胞百分率增加，而NO供体二乙三胺-一氧化氮加合物(DETA-NO)可抑制细胞增殖，但不影响细胞凋亡。L的名字治疗也改变了分化模式，导致神经元数量的扩大。结果提示，内源性NO可能通过调节SVZ祖细胞的增殖和命运而参与生后神经发生。(C)2003爱思唯尔B.V.保留所有权利。
The subventricular zone (SVZ) of rodents retains the capacity to generate new neurons throughout the entire life of the animal. Neural progenitors of the SVZ survive and proliferate in vitro in the presence of epidermal growth factor (EGF). Nitric oxide (NO) has been shown to participate in neural tissue formation during development and to have antiproliferative actions, mediated in part by inhibition of the EGF receptor. Based on these findings, we have investigated the possible effects of endogenously produced and endogenously added NO on SVZ cell proliferation and differentiation. Explants were obtained from postnatal mouse SVZ and cultured in the presence of EGF. Cells migrated out of the explants and proliferated in culture, as assessed by bromodeoxyuridine (BrdU) incorporation. After 72 h in vitro, the colonies formed around the explants were constituted by cells of neuronal or glial lineages, as well as undifferentiated progenitors. Immunoreactivity for the neuronal isoform of NO synthase was observed in neuronal cells with long varicose processes. Cultures treated with the NOS inhibitor N-omega-nitro-(L)-arginine methyl ester (L-NAME) showed an increase in the percentage of BrdU-immunoreactive cells, whereas treatment with the NO donor diethylenetriamine-nitric oxide adduct (DETA-NO) led to a decrease in cell proliferation, without affecting apoptosis. The differentiation pattern was also altered by L-NAME treatment resulting in an enlargement of the neuronal population. The results suggest that endogenous NO may contribute to postnatal neurogenesis by modulating the proliferation and fate of SVZ progenitor cells. (C) 2003 Elsevier B.V. All rights reserved.