Amyloid fibrils induce dysfunction of hippocampal glutamatergic silent synapses.
Amyloid fibrils induce dysfunction of hippocampal glutamatergic silent synapses.
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DOI：
10.1002/hipo.22955
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发表时间：
2018-08
期刊：
影响因子：
3.5
通讯作者：
Naguib M
中科院分区：
文献类型：
--
作者：
Bie B;Wu J;Foss JF;Naguib M
缺乏功能性AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐）受体的沉默谷氨酸能突触存在于包括海马在内的多个大脑区域。它们参与阿尔茨海默病（AD）背景下海马神经递质传递功能障碍的情况尚不清楚。本研究表明，在大鼠海马CA 1区微量注射淀粉样纤维（Aβ1-40）后，沉默突触的百分比降低。此外，配对低频电刺激未能诱导激活海马沉默突触在模型大鼠。免疫印迹研究显示，海马CA 1区突触体制备中GluR 1亚基的表达减少，表明建模大鼠突触后密度中GluR 1亚基锚定的潜在减少。我们还注意到，在注射Aβ1-40的大鼠中，磷酸化cofilin的表达降低，其调节肌动蛋白细胞骨架和受体运输的功能，并且支架蛋白PSD 95在海马CA 1突触体中的表达降低。综上所述，本研究阐明了AD啮齿动物模型中海马沉默突触的功能障碍，这可能是淀粉样纤维诱导的肌动蛋白细胞骨架和突触后支架蛋白的损伤所致。
Silent glutamatergic synapses lacking functional AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors exist in several brain regions including the hippocampus. Their involvement in the dysfunction of hippocampal glutamatergic transmission in the setting of Alzheimer’s disease (AD) is unknown. The present study demonstrated a decrease in the percentage of silent synapses in rats microinjected with amyloid fibrils (Aβ1–40) into the hippocampal CA1. Also, pairing low-frequency electric stimuli failed to induce activation of the hippocampal silent synapses in the modeled rats. Immunoblotting studies revealed a decreased expression of GluR1 subunits in the hippocampal CA1 synaptosomal preparation, indicating a potential reduction in the GluR1 subunits anchoring in postsynaptic density in the modeled rats. We also noted a decreased expression of phosphorylated cofilin, which regulates the function of actin cytoskeleton and receptor trafficking, and reduced expression of the scaffolding protein PSD95 in the hippocampal CA1 synaptosome in rats injected with Aβ1–40. Taken together, the present study illustrates dysfunction of hippocampal silent synapse in the rodent model of AD, which might result from the impairments of actin cytoskeleton and postsynaptic scaffolding proteins induced by amyloid fibrils.
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影响因子：
4.4
作者：
Iasevoli, Felice;Tomasetti, Carmine;de Bartolomeis, Andrea
通讯作者：
de Bartolomeis, Andrea
影响因子：
5.7
作者：
Anggono V;Huganir RL
通讯作者：
Huganir RL
影响因子：
25
作者：
Gu, Jiaping;Lee, Chi Wai;Fan, Yanjie;Komlos, Daniel;Tang, Xin;Sun, Chicheng;Yu, Kuai;Hartzell, H. Criss;Chen, Gong;Bamburg, James R.;Zheng, James Q.
通讯作者：
Zheng, James Q.
DOI：
10.1124/jpet.108.148908
发表时间：
2009-04-01
影响因子：
3.5
作者：
Bie, Bihua;Zhu, Wei;Pan, Zhizhong Z.
通讯作者：
Pan, Zhizhong Z.
影响因子：
64.8
作者：
LIAO, DZ;HESSLER, NA;MALINOW, R
通讯作者：
MALINOW, R