Ampakines promote spine actin polymerization, long-term potentiation, and learning in a mouse model of Angelman syndrome.
Ampakines promote spine actin polymerization, long-term potentiation, and learning in a mouse model of Angelman syndrome.
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安丙定促进脊柱肌动蛋白聚合，长期增强和在Angelman综合征的小鼠模型中学习。
DOI：
10.1016/j.nbd.2012.04.002
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发表时间：
2012-08
影响因子：
6.1
通讯作者：
Bi X
中科院分区：
文献类型：
--
作者：
Baudry M;Kramar E;Xu X;Zadran H;Moreno S;Lynch G;Gall C;Bi X
Angelman syndrome (AS) is a neurodevelopmental disorder largely due to abnormal maternal expression of the UBE3A gene leading to the deletion of E6-associated protein. AS subjects have severe cognitive impairments for which there are no therapeutic interventions. Mouse models (knockouts of the maternal Ube3a gene: ‘AS mice’) of the disorder have substantial deficits in long-term potentiation (LTP) and learning. Here we report a clinically plausible pharmacological treatment that ameliorates both deficits. AS mice were injected ip twice daily for 5 days with vehicle or the ampakine CX929; drugs of this type enhance fast EPSCs by positively modulating AMPA receptors. Theta burst stimulation (TBS) produced a normal enhancement of field EPSPs in hippocampal slices prepared from vehicle-treated AS mice but LTP decreased steadily to baseline; however, LTP in slices from ampakine-treated AS mice stabilized at levels found in wild-type controls. TBS-induced actin polymerization within dendritic spines, an essential event for stabilizing LTP, was severely impaired in slices from vehicle-treated AS mice but not in those from ampakine-treated AS mice. Long-term memory scores in a fear conditioning paradigm were reduced by 50% in vehicle-treated AS mice but were comparable to values for littermate controls in the ampakine-treated AS mice. We propose that AS is associated with a profound defect in activity-driven spine cytoskeletal reorganization, resulting in a loss of the synaptic plasticity required for the encoding of long-term memory. Notably, the spine abnormality along with the LTP and learning impairments can be reduced by a minimally invasive drug treatment.
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影响因子：
6.1
作者：
Simmons, Danielle A.;Mehta, Rishi A.;Lauterborn, Julie C.;Gall, Christine M.;Lynch, Gary
通讯作者：
Lynch, Gary
影响因子：
64.5
作者：
SCHEFFNER, M;HUIBREGTSE, JM;HOWLEY, PM
通讯作者：
HOWLEY, PM
DOI：
10.1073/pnas.0811228106
发表时间：
2009-03-24
影响因子：
11.1
作者：
Simmons, Danielle A.;Rex, Christopher S.;Lynch, Gary
通讯作者：
Lynch, Gary
影响因子：
2.5
作者：
Rex, Christopher S.;Lauterborn, Julie C.;Lynch, Gary
通讯作者：
Lynch, Gary
DOI：
10.1002/ajmg.1320350308
发表时间：
1990-03-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
WILLIAMS, CA;ZORI, RT;OSTRER, H
通讯作者：
OSTRER, H