A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three‐dimensional ultrastructural study

A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three‐dimensional ultrastructural study
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细胞粘附分子模拟物 FGL 肽诱导老年大鼠齿状回突触和树突棘结构的改变:三维超微结构研究

DOI:
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发表时间:
2008
影响因子:
3.4
通讯作者:
M. Stewart
M. Stewart
中科院分区:
医学3区
文献类型:
--
作者:
V. Popov;N. Medvedev;I. Kraev;Paul Leonard Gabbott;H. Davies;M. Lynch;T. Cowley;V. Berezin;E. Bock;M. Stewart

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FGL肽是一种神经细胞粘附分子(NCAM)模拟物,包含NCAM第二个纤连蛋白III型模块FG环区的15个氨基酸长序列。 它对应于NCAM对成纤维细胞生长因子受体1的结合位点。 FGL通过增强突触功能改善认知功能。我们检查了FGL对老龄(22月龄)大鼠脑中突触和树突结构的影响,这些大鼠以2天间隔皮下注射(8 mg/kg),直至实验开始后19天。  用固定剂灌注动物,取出大脑,并以50 µm切割冠状切片。 测量海马体积,组织包埋并在JEOL 1010电子显微镜下观察切片。 通过一系列100个连续切片的图像进行三维重建后,对突触和树突参数进行分析。FGL既不影响海马体积,也不影响齿状回中分子层的棘或突触密度。但是,它增加了蘑菇与薄刺的比例,多泡体的数量,也增加了被纹孔的出现频率。三维分析显示,FGL处理后蘑菇棘的突触后密度和并置区曲率均显著降低,而对于薄棘,并置区的凸度增加。这些数据表明,FGL诱导老年大鼠海马中突触和树突棘的精细结构的巨大变化,补充了显示其对认知过程的影响的数据。
The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15‐amino‐acid‐long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22‐month‐old) rats that were injected subcutaneously (8 mg/kg) at 2‐day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains removed and coronal sections cut at 50 µm. The hippocampal volume was measured, tissue embedded and ultrathin sections viewed in a JEOL 1010 electron microscope. Analyses were made of synaptic and dendritic parameters following three‐dimensional reconstruction via images from a series of ∼100 serial ultrathin sections. FGL affected neither hippocampal volume nor spine or synaptic density in the middle molecular layer of the dentate gyrus. However, it increased the ratio of mushroom to thin spines, number of multivesicular bodies and also increased the frequency of appearance of coated pits. Three‐dimensional analysis showed a significant decrease in both post‐synaptic density and apposition zone curvature of mushroom spines following FGL treatment, whereas for thin spines the convexity of the apposition zone increased. These data indicate that FGL induces large changes in the fine structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes.
DOI: 10.1126/science.284.5421.1811
发表时间: 1999-06-11
期刊: SCIENCE
影响因子: 56.9
作者:
Shi, SH;Hayashi, Y;Malinow, R
通讯作者: Malinow, R
DOI: 10.1093/cercor/10.10.952
发表时间: 2000-10-01
期刊: CEREBRAL CORTEX
影响因子: 3.7
作者:
Geinisman, Y
通讯作者: Geinisman, Y