Amyloid beta from axons and dendrites reduces local spine number and plasticity.
Amyloid beta from axons and dendrites reduces local spine number and plasticity.
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DOI：
10.1038/nn.2476
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发表时间：
2010-02
影响因子：
25
通讯作者：
Malinow, Roberto
中科院分区：
文献类型：
--
作者：
Wei, Wei;Nguyen, Louis N.;Kessels, Helmut W.;Hagiwara, Hiroaki;Sisodia, Sangram;Malinow, Roberto
突触过度丧失被认为是阿尔茨海默病最早的事件之一。 β 淀粉样蛋白 (Aβ) 是一种由神经元以活性调节方式分泌的肽，通过消除树突棘（兴奋性突触传递部位）而与阿尔茨海默病的发病机制有关。然而，有关 Aβ 的亚细胞来源及其产生机制和导致突触损失的作用的问题仍然知之甚少。在大鼠器官切片中，我们发现轴突或树突 Aβ 的急剧过量产生会降低附近（~5-10 µm）树突的脊柱密度和可塑性。 Aβ 的产生及其对脊柱的影响对动作电位或烟碱受体的阻断敏感； Aβ 的作用（但不是其产生）对 NMDA 受体阻断敏感。值得注意的是，只有 30-60 分钟的 Aβ 过量生产阻断才能诱导可塑性。我们的结果表明，树突或轴突中 Aβ 的持续过量产生会局部减少突触的数量和可塑性。
Excessive synaptic loss is thought to be one of the earliest events in Alzheimer’s disease. Amyloid beta (Aβ), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of Alzheimer’s disease by removing dendritic spines, sites of excitatory synaptic transmission. However, issues regarding the subcellular source of Aβ, as well as the mechanisms of its production and actions that lead to synaptic loss, remain poorly understood. In rat organotypic slices, we found that acute overproduction of either axonal or dendritic Aβ reduced spine density and plasticity at nearby (~5–10 µm) dendrites. The production of Aβ and its effects on spines were sensitive to blockade of action potentials or nicotinic receptors; the effects of Aβ (but not its production) were sensitive to NMDA receptor blockade. Notably, only 30–60 min blockade of Aβ overproduction permitted induction of plasticity. Our results indicate that continuous overproduction of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses.
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影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
4.8
作者：
Dineley, KT;Bell, KA;Sweatt, JD
通讯作者：
Sweatt, JD
影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T
DOI：
10.1073/pnas.0600948103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Jacobsen, JS;Wu, CC;Bloom, FE
通讯作者：
Bloom, FE