Three-Dimensional Synaptic Ultrastructure in the Dentate Gyrus and Hippocampal Area CA3 in the Ts65Dn Mouse Model of Down Syndrome
Three-Dimensional Synaptic Ultrastructure in the Dentate Gyrus and Hippocampal Area CA3 in the Ts65Dn Mouse Model of Down Syndrome
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DOI：
10.1002/cne.22573
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发表时间：
2011-05-01
影响因子：
2.5
通讯作者：
Belichenko, Pavel V.
中科院分区：
文献类型：
--
作者：
Popov, Victor I.;Kleschevnikov, Alexander M.;Belichenko, Pavel V.
唐氏综合症是由人类21号染色体三体引起的。Ts65Dn小鼠是一种已建立的DS模型，其表现出与DS患者相似的几种表型。然而，关于海马三突触通路中突触结构可塑性的数据很少。本文研究了年龄匹配对照（2N）和Ts65Dn雄性小鼠海马突触的三维超微结构。连续超薄切片和三维重建表征了CA3锥体神经元齿状回中间分子层（MML）和顶端树突近端多刺赘生物（TEs）中的突触。三维突触分析显示了Ts65Dn小鼠与2N小鼠的表型差异。对于MML， Ts65Dn小鼠的突触密度比2N小鼠减少15% （P < 0.05）。3D对比分析显示，Ts65Dn小鼠与2N小鼠相比，CA3中每TE的刺数显著减少（约45%，P = 0.01）。单根刺体积Ts65Dn组比2N组小3倍（P = 0.02）。与2N小鼠相比，Ts65Dn小鼠每个TE的刺突数量显著减少，TE表面丝状突起减少（P = 0.02）。而CA3 Ts65Dn和2N小鼠的突触后密度体积没有变化（P = 0.78）。研究结果表明，CA3刺的高度可塑性可能与其丝状起源有关。Ts65Dn小鼠三维突触结构的改变可能进一步导致DS可塑性降低。中国生物医学工程学报，2016,31(2):444 - 444。(C) 2010 Wiley-Liss, Inc。
Down syndrome (DS) results from trisomy of human chromosome 21. Ts65Dn mice are an established model for DS and show several phenotypes similar to those in people with DS. However, there is little data on the structural plasticity of synapses in the trisynaptic pathway in the hippocampus. Here we investigate 3D ultrastructure of synapses in the hippocampus of age-matched control (2N) and Ts65Dn male mice. Serial ultrathin sections and 3D reconstructions characterize synapses in the middle molecular layer (MML) of dentate gyrus and in thorny excrescences (TEs) in proximal portions of apical dendrites of CA3 pyramidal neurons. 3D analysis of synapses shows phenotypes that distinguish Ts65Dn from 2N mice. For the MML, synapse density was reduced by 15% in Ts65Dn vs. 2N mice (P < 0.05). Comparative 3D analyses demonstrate a significant decrease in the number of thorns per TE in CA3 in Ts65Dn vs. 2N mice (by approximate to 45%, P = 0.01). Individual thorn volume was 3 times smaller in Ts65Dn vs. 2N mice (P = 0.02). A significant decrease in the number of thorn projections per TE in Ts65Dn vs. 2N mice was accompanied by a decrease of filopodium-like protrusions on the surface of TEs (P = 0.02). However, the volume of postsynaptic densities in CA3 Ts65Dn and 2N mice was unchanged (P = 0.78). Our findings suggest that the high degree of plasticity of CA3 thorns may be connected with their filopodial origin. Alterations of 3D synaptic structure in Ts65Dn mice may further contribute to the diminished plasticity in DS. J. Comp. Neurol. 519: 1338-1354, 2011. (C) 2010 Wiley-Liss, Inc.