REGIONAL DISTRIBUTION OF NEURAL CELL-ADHESION MOLECULE (N-CAM) AND L1 IN HUMAN AND RODENT HIPPOCAMPUS

REGIONAL DISTRIBUTION OF NEURAL CELL-ADHESION MOLECULE (N-CAM) AND L1 IN HUMAN AND RODENT HIPPOCAMPUS
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DOI:
10.1002/cne.903270303
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发表时间:
1993-01-15
影响因子:
2.5
通讯作者:
DEKOSKY, ST
DEKOSKY, ST
中科院分区:
医学3区
文献类型:
--
作者:
MILLER, PD;CHUNG, WW;DEKOSKY, ST

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在体外和体内发育研究中,细胞表面粘附分子N-CAM和L1涉及中枢神经系统(CNS)细胞迁移和轴突生长。这些分子在中枢神经系统发育过程中表现出不同的分布,从而表明它们在过程生长和组织中发挥不同的作用。已知多种N-CAM同种型,并且单个N-CAM经历翻译后修饰。这种变化和产生许多分子的潜力可能介导特定神经细胞接触和电路的发展。我们评估了针对L1和N-CAM的多克隆抗体以及针对胚胎N-CAM和人、大鼠和小鼠海马中的140和180 kDa种类的N-CAM的单克隆抗体的免疫组织化学染色。在这三个物种的染色模式是定性相似的,但在小鼠海马染色的定量更大的一些表位。发现了一种独特的染色模式,与已知的结构解剖相对应。总N-CAM染色在齿状回门和内分子层(ML)中较强,在齿状回外ML中染色较轻。苔藓纤维束(MFT),包括从齿状颗粒细胞到CA 3锥体细胞的轴突,强烈的N-CAM的多克隆抗体染色。CA 1的放射层(SR)和起始层(SO)染色丰富,而分子陷窝层(LM)染色很少。识别140和180 kDa形式的N-CAM的单克隆抗体12 F11强烈染色MFT、门和内ML。使用12 F11,SO和SR在整个CA 1中均匀染色,在CA 2和CA 3中染色大大减少。光镜下可见少量染色。L1染色在整个海马和齿状回分布较均匀,门和MFT染色较浅,SR和SO染色均匀。LM层L1染色强烈,SR和LM之间有一个狭窄的透明区。齿状回的ML用抗L1强烈染色,内部和外部ML之间有一个分离的透明区。胚胎N-CAM在CA 1中几乎没有染色,但在肺门和MFT中有很强的染色;因此,这种“胚胎"决定簇继续在成人的有限区域中表达。与成年啮齿动物海马相反,人类海马在ML的外三分之二处显示出胚胎N-CAM,但在门区显示出非常少的染色。这些独特的模式表明,N-CAM和L1分子种类的分布在海马的分层电路中具有明确的结构和功能作用。
Cell surface adhesion molecules N-CAM and Ll are implicated in central nervous system (CNS) cell migration and axon outgrowth in in vitro and in vivo developmental studies. These molecules show a differential distribution during CNS development, thus suggesting that they subserve different roles in process outgrowth and tissue organization. A variety of N-CAM isoforms are known, and individual N-CAMs undergo posttranslational modification. Such changes and the potential for generating numerous molecules may mediate development of specific neural cell contacts and circuitry. We evaluated immunohistochemical staining of polyclonal antibodies to Ll and N-CAM, as well as monoclonal antibodies directed against embryonic N-CAM and the 140 and 180 kDa species of N-CAM in human, rat, and mouse hippocampus. Staining patterns in the three species were qualitatively similar, but staining in the mouse hippocampus was quantitatively greater for some epitopes. A distinctive pattern of staining was found, corresponding to the known anatomy of the structure. Total N-CAM staining was intense in the hilus and inner molecular layer (ML) of the dentate gyrus with lighter staining in the dentate outer ML. The mossy fiber tract (MFT), comprising axons traveling from the dentate granule cells to CA3 pyramidal cells, was strongly stained by polyclonal antibody to N-CAM. There was abundant staining of the stratum radiatum (SR) and stratum oriens (SO) of CA1, but stratum lacunosum moleculare (LM) showed very little staining. The monoclonal antibody 12F11, which recognizes the 140 and 180 kDa forms of N-CAM, intensely stained the MFT, hilus, and inner ML. With 12F11, SO and SR stained uniformly throughout CA1, with much reduced staining in CA2 and CA3. There was little staining in LM. L1 staining was more evenly distributed throughout the hippocampus and dentate, with light hilar and MFT staining, and even staining through the SR and SO. Stratum LM stained intensely for L1, with a narrow clear zone between SR and LM. The ML of the dentate gyrus stained intensely with anti-L1, with a discrete clear zone separating the inner and outer ML. Embryonic N-CAM had little staining in CA1 but strong hilar and MFT staining; thus, this ''embryonic'' determinant continues to be expressed in limited regions in the adult. In contrast to the adult rodent hippocampus, human hippocampus exhibited embryonic N-CAM in the outer two-thirds of the ML, but showed very little staining in the hilar region. These distinctive patterns suggest that the distribution of the N-CAM and Ll molecular species have clear-cut structural and functional roles in the laminated circuitry of the hippocampus.