Polysialic Acid Regulates the Clustering, Migration, and Neuronal Differentiation of Progenitor Cells in the Adult Hippocampus
Polysialic Acid Regulates the Clustering, Migration, and Neuronal Differentiation of Progenitor Cells in the Adult Hippocampus
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DOI：
10.1002/dneu.20681
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发表时间：
2008-12-01
影响因子：
3
通讯作者：
Aubert, Isabelle
中科院分区：
文献类型：
--
作者：
Burgess, Alison;Wainwright, Steven R.;Aubert, Isabelle
海马成体齿状回新生细胞的特点是大量表达聚唾液酸（PSA），这是一种附着在神经细胞粘附分子（NCAM）上的碳水化合物。齿状回的PSA+新生细胞与增殖的神经祖细胞形成集群，并从这些集群中迁移，最终分化。为了确定PSA在齿状回成年祖细胞发育中的作用，我们在成年大鼠海马中注射内神经氨酸酶N （endoN）特异性地从NCAM中分离PSA。两天后，我们给予有丝分裂标记物5-溴-2'-脱氧尿苷（BrdU）。注射BrdU 3 d后，新生细胞簇内外均可见BrdU+细胞。在endon处理的动物中，BrdU+细胞的总数没有改变，但簇内存在明显更多的BrdU+细胞，这表明PSA通常促进祖细胞远离簇的迁移。注射BrdU 7天后，与对照组相比，endon处理动物的BrdU+细胞数量明显增加，且成熟神经元核标记物NeuN呈阳性，表明祖细胞中PSA的缺失增加了神经元的分化。本报告首次证实PSA参与控制正常大脑成年海马祖细胞的时空神经元成熟。在体外实验中，从成人来源的神经祖细胞中去除PSA显著增强了神经元分化，强化了我们在体内的研究结果，表明去除分离的祖细胞上的PSA，除了复杂的体内环境外，还会诱导神经元成熟。(c) 2008 Wiley期刊。公司。中国生物医学工程学报，38 (2):559 - 559
Newborn cells of the adult dentate gyros in the hippocampus are characterized by their abundant expression of polysialic acid (PSA), a carbohydrate attached to the neural cell adhesion molecule (NCAM). PSA+ newborn cells of the dentate gyros form clusters with proliferating neural progenitor cells, migrate away from these clusters, and terminally differentiate. To identify the roles of PSA in the development of adult progenitors of the dentate gyrus, we injected endoneuraminidase N (endoN) into the hippocampus of adult rats to specifically cleave PSA from NCAM. Two days later, we administered the mitotic marker, 5-bromo-2'-deoxyuridine (BrdU). Three days after BrdU injection, BrdU+ cells were found inside and outside the clusters of newborn cells. In endoN-treated animals', the total number of BrdU+ cells was not changed but significantly more BrdU+ cells were present within clusters, suggesting that PSA normally facilitates the migration of progenitors away from the clusters. Seven days post-BrdU injection, endoN-treated animals had significantly more BrdU+ cells which were also positive for the mature neuronal nuclear marker NeuN compared with controls, indicating that the loss of PSA from progenitor cells increases neuronal differentiation. This report is the first demonstration that PSA is involved in controlling the spatio-temporal neuronal maturation of adult hippocampal progenitors in the normal brain. In vitro, the removal of PSA from adult-derived neural progenitors significantly enhanced neuronal differentiation, strengthening our in vivo findings and indicating that PSA removal on isolated progenitor cells, apart from a complex in vivo environment, induces neuronal maturation. (c) 2008 Wiley Periodicals. Inc. Develop Neurobiol 68: 1580-1590.2008