Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo
Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo
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DOI：
10.1016/s0736-5748(01)00012-0
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发表时间：
2001-06-01
影响因子：
1.8
通讯作者：
Schliebs, R
中科院分区：
文献类型：
--
作者：
Kirazov, E;Kirazov, L;Schliebs, R
为了阐明淀粉样前体蛋白（APP）在脑个体发育过程中的功能作用，APP水平在生长锥和突触体的发育变化进行了研究，从胚胎第14天到出生后（PD）400天，使用Western分析。在产前发育阶段，生长锥中的APP水平较低，但从PD 3到PD 10持续增加。在PD 7和10之间发现突触体中APP的最高浓度，随后在PD 30之前显著降低，并在PD 400之前持续该水平。原位杂交，以区分APP 695 mRNA，APP 751 mRNA和APP 770 mRNA显示不同的APP亚型的年龄相关的表达模式。在产前大脑发育期间，APP 695 mRNA在包含分化神经细胞的大脑结构中最大程度地表达。APP 751和APP 770 mRNA亚型在整个产前检查期间广泛分布于胚胎中，与脑相比，其在外周器官如皮肤、肺、肝脏和骨骼中的表达更高。在突触发生过程中APP水平的增加表明APP在神经突生长和细胞靶向过程中以及在成熟脑中维持突触功能完整性中的功能作用。APP 695亚型似乎是参与胚胎脑成熟的主要形式。(C)2001 ISDN。由爱思唯尔科技有限公司出版。保留所有权利。
To elucidate the functional role of the amyloid precursor protein (APP) during brain ontogeny, developmental changes of APP levels in growth cones and synaptosomes were studied from embryonic day 14 up to postnatal day (PD) 400 using Western analysis. APP level in growth cones was low during prenatal stages of development, but demonstrating a continuous increase from PD 3 up to PD 10. Highest concentration of APP in synaptosomes was found between PD 7 and 10, followed by a considerable decrease up to PD 30 and persisting at this level up to PD 400. In situ hybridization to differentiate between APP695 mRNA, APP751 mRNA and APP770 mRNA revealed distinct age-related expression pattern of various APP isoforms. During prenatal brain development APP695 mRNA is maximally expressed in brain structures, containing differentiating nerve cells. APP751 and APP770 mRNA isoforms are diffusely distributed in the embryo throughout the prenatal period examined and their expression is higher in peripheral organs such as skin, lung, liver and bones as compared to the brain. The increase of APP level during synaptogenesis suggests a functional role of APP in the processes of neurite outgrowth and cell targeting as well as in the maintenance of the functional integrity of synapses in the mature brain. The APP695 isoform seems to be the major form involved in embryonic brain maturation. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.