Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome
Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome
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DOI：
10.1002/cne.20337
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发表时间：
2004-12-13
影响因子：
2.5
通讯作者：
Mobley, WC
中科院分区：
文献类型：
--
作者：
Belichenko, PV;Masliah, E;Mobley, WC
Ts65Dn小鼠是唐氏综合症的遗传模型。尽管这只小鼠表现出认知功能异常，这牵涉到海马体，以及海马体长时程增强的明显缺陷，但对海马体的结构研究很少。我们研究了Ts65Dn和对照组(2N)小鼠的突触结构，研究了海马区(齿状筋膜，CA1)以及运动和躯体感觉皮质、内嗅觉皮质和内侧隔。用共聚焦显微镜观察免疫组织化学染色的突触前突触，并观察微量注射荧光黄后树突的结构。Ts65Dn各脑区突触前和突触后成分均明显增大。这些变化是在接受检查的最小年龄(出生后第21天)和成年人中检测到的。在详细描述齿状筋膜和运动皮质变化的研究中，脊柱的增大影响了整个人群，导致脊柱的存在，其体积大大增加。电子显微镜证实，脊椎和脊椎增大，内膜异常。此外，齿状颗粒细胞的树突上的棘密度降低，抑制输入的重组，树突干的输入相对减少，棘颈的输入增加。综上所述，这些发现记录了突触结构的广泛异常，概括了唐氏综合症的重要特征。他们建立了Ts65Dn小鼠作为唐氏综合症突触结构和功能异常的模型，并指出了研究解释突触扩大的机制的重要性。(C)2004年Wiley-Liss公司
The Ts65Dn mouse is a genetic model for Down syndrome. Although this mouse shows abnormalities in cognitive function that implicate hippocampus as well as marked deficits in hippocampal long-term potentiation, the structure of the hippocampus has been little studied. We characterized synaptic structure in Ts65Dn and control (2N) mice, studying the hippocampus (fascia dentata, CA1) as well as the motor and somatosensory cortex, entorhinal cortex, and medial septum. Confocal microscopy was used to examine immunostained presynaptic boutons and to detail the structure of dendrites after Lucifer yellow microinjection. Both presynaptic and postsynaptic elements were significantly enlarged in Ts65Dn in all regions examined. The changes were detected at the youngest age examined (postnatal day 21) and in adults. In studies detailing the changes in fascia dentata and motor cortex, the enlargement of spines affected the entire population, resulting in the presence of spines whose volume was greatly increased. Electron microscopy confirmed that boutons and spines were enlarged and demonstrated abnormalities in the internal membranes of both. In addition, spine density was decreased on the dendrites of dentate granule cells, and there was reorganization of inhibitory inputs, with a relative decrease in inputs to dendrite shafts and an increase in inputs to the necks of spines. Taken together, the findings document widespread abnormalities of synaptic structure that recapitulate important features seen in Down syndrome. They establish the Ts65Dn mouse as a model for abnormal synapse structure and function in Down syndrome and point to the importance of studies to elucidate the mechanisms responsible for synapse enlargement. (C) 2004 Wiley-Liss, Inc.