Excitatory-Inhibitory Relationship in the Fascia Dentata in the Ts65Dn Mouse Model of Down Syndrome
Excitatory-Inhibitory Relationship in the Fascia Dentata in the Ts65Dn Mouse Model of Down Syndrome
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DOI：
10.1002/cne.21895
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发表时间：
2009-02-01
影响因子：
2.5
通讯作者：
Mobley, William C.
中科院分区：
文献类型：
--
作者：
Belichenko, Pavel V.;Klescrevnikov, Alexander M.;Mobley, William C.
唐氏综合症（DS）是一种导致学习和记忆受损的神经系统疾病。部分 16 三体小鼠 (Ts65Dn) 是 DS 的遗传模型。此前，我们证明了 Ts65Dn 小鼠突触前和突触后元件的广泛改变以及生理异常。新皮质和海马突触前束和棘的平均直径增大。观察到由于过度抑制而导致长时程增强 (LTP) 诱导失败。在本文中，我们研究了 Ts65Dn 过度抑制的形态底物。我们使用电子显微镜（EM）来表征突触，共聚焦显微镜来分析突触小泡蛋白的一般标记与抑制性和兴奋性突触的特定蛋白质标记的共定位，并使用光密度测定来表征受体和神经递质受体突触聚类所必需的几种蛋白质的分布。 Ts65Dn 与 2N 中突触的 EM 分析表明，对称突触的突触相对长度显着更大（类似于 18%），但不对称突触则不然。总体而言，发现谷氨酸脱羧酶 (GAD)65/p38 免疫反应性 (IR)（接近 27%）和囊泡 GABA 转运蛋白（VGAT）/p38 IR（接近 41%）的共定位系数显着增加，但囊泡谷氨酸转运蛋白 1 (VGLUT1)/p38 1R 的共定位系数没有显着增加。与 2N 小鼠相比，Ts65Dn 小鼠海马谷氨酸受体 2（GluR2；类似于 13%）和抗γ-氨基丁酸（GABA）（A）受体 P2/3 亚基（类似于 20%）的 IR 整体显着降低。对受体突触聚集所必需的蛋白质的研究表明，neuroligin 2（类似于 13%）和 GABA(A) 受体相关蛋白（GABARAP；类似于 13%）的泪点大小显着增加，但 Neuroligin 1 和 gephyrin 则没有。结果表明 Ts65Dn 小鼠齿状筋膜中的抑制性突触发生显着改变。 J.Comp。内罗尔。 512：453-466，2009。 (c) 2008 年 Wiley-Liss, Inc.
Down syndrome (DS) is a neurological disorder causing impaired learning and memory. Partial trisomy 16 mice (Ts65Dn) are a genetic model for DS. Previously, we demonstrated widespread alterations of pre- and postsynaptic elements and physiological abnormalities in Ts65Dn mice. The average diameter of presynaptic boutons and spines in the neocortex and hippocampus was enlarged. Failed induction of long-term potentiation (LTP) due to excessive inhibition was observed. In this paper we investigate the morphological substrate for excessive inhibition in Ts65Dn. We used electron microscopy (EM) to characterize synapses, confocal microscopy to analyze colocalization of the general marker for synaptic vesicle protein with specific protein markers for inhibitory and excitatory synapses, and densitometry to characterize the distribution of the receptor and several proteins essential for synaptic clustering of neurotransmitter receptors. EM analysis of synapses in the Ts65Dn vs. 2N showed that synaptic opposition lengths were significantly greater for symmetric synapses (similar to 18%), but not for asymmetric ones. Overall, a significant increase in colocalization coefficients of glutamic acid decarboxylase (GAD)65/p38 immunoreactivity (IR) (similar to 27%) and vesicular GABA transporter (VGAT)/p38 IR (similar to 41 %) was found, but not in vesicular glutamate transporter 1 (VGLUT1)/p38 1R. A significant overall decrease of IR in the hippocampus of Ts65Dn mice compared with 2N mice for glutamate receptor 2 (GluR2; similar to 13%) and anti-gamma-aminobutyric acid (GABA)(A) receptor P2/3 subunit (similar to 20%) was also found. The study of proteins essential for synaptic clustering of receptors revealed a significant increase in puncta size for neuroligin 2 (similar to 13%) and GABA(A) receptor-associated protein (GABARAP; similar to 13%), but not for neuroligin 1 and gephyrin. The results demonstrate a significant alteration of inhibitory synapses in the fascia dentata of Ts65Dn mice. J. Comp. Neurol. 512: 453-466,2009. (c) 2008 Wiley-Liss, Inc.