Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.
Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.
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DOI：
10.1371/journal.pone.0102978
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Halpain S
中科院分区：
文献类型：
--
作者：
Platholi J;Herold KF;Hemmings HC Jr;Halpain S
全身麻醉药通过调节兴奋性和抑制性突触传递产生可逆的昏迷状态。最近的证据表明，麻醉剂暴露也会导致持续的认知功能障碍。然而，麻醉剂对已建立的突触结构的亚细胞影响尚不清楚。我们研究了广泛使用的挥发性麻醉剂异氟烷对海马树突棘结构稳定性的影响，海马树突棘是一种对学习和记忆中的兴奋性突触传递至关重要的突触后结构。暴露于临床浓度的异氟醚会导致成熟培养的大鼠海马神经元树突棘快速且不均匀的收缩和丧失。脊柱收缩与脊柱 F-肌动蛋白浓度降低有关。 jasplakinolide 或 cytochalasin D（可防止 F-肌动蛋白分解的药物）可以防止脊柱损失。异氟烷引起的脊柱收缩和损失在异氟烷消除后是可逆的。因此，异氟烷会破坏树突棘 F-肌动蛋白的稳定性，导致树突棘形态和数量发生变化。这些发现支持基于肌动蛋白的异氟烷诱导海马突触结构改变的机制。树突棘结构的这些可逆改变对于急性麻醉对海马（麻醉剂引起的遗忘症的场所）的兴奋性突触传递和突触稳定性的影响具有重要意义，并且对于麻醉对突触可塑性的影响也具有重要意义。
General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.
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树突稳定性的分子机制。
影响因子：
34.7
作者：
Koleske, Anthony J.
通讯作者：
Koleske, Anthony J.
影响因子：
16.2
作者：
Frost, Nicholas A.;Shroff, Hari;Kong, Huihui;Betzig, Eric;Blanpied, Thomas A.
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DOI：
10.1073/pnas.96.18.10433
发表时间：
1999-08-31
影响因子：
11.1
作者：
Kaech, S;Brinkhaus, H;Matus, A
通讯作者：
Matus, A
影响因子：
7.8
作者：
COOPER, JA;BLUM, JD;POLLARD, TD
通讯作者：
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影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T