Persistent LTP without triggered protein synthesis

Persistent LTP without triggered protein synthesis
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DOI:
10.1016/j.neures.2008.10.008
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发表时间:
2009-01-01
影响因子:
2.9
通讯作者:
Wigstrom, Holger
Wigstrom, Holger
中科院分区:
医学4区
文献类型:
--
作者:
Abbas, Abdul-Karim;Dozmorov, Mikhail;Wigstrom, Holger

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蛋白质合成被认为与突触可塑性的稳定有关。持续时间超过2-3小时的影响被认为需要合成新的蛋白质,这意味着早期(E)和晚期(L)组分之间的功能分离。然而,构成蛋白与新蛋白合成的问题仍不清楚,特别是在幼龄动物中。在这里,我们检查了两种蛋白质合成抑制剂,大霉素和艾美汀的作用。对12 ~ 20日龄大鼠海马CA1区长期增强(LTP)的影响。对于LTP诱导,两种药物的应用时间均为-30分钟至+30分钟,这是先前报道的关键时间窗口。然而,LTP在整个记录期间(4 h(大霉素)或8 h(艾美汀))保持稳定。在单独的实验中,适当制备艾美汀溶液可以证明,延长艾美汀治疗会逐渐阻断基线反应。虽然没有观察到与大霉素相应的效果,但通过其抑制酵母生长的能力,该药物被认为是有效的。通过评估亮氨酸掺入程度的放射性标记实验,进一步证实了大霉素抑制蛋白质合成的能力。我们的数据表明,至少8小时的LTP不依赖于触发的蛋白质合成,而是可以通过利用诱导时已经可用的蛋白质来获得。(C) 2008爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3 h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue Of constitutive vs. new protein synthesis is still unclear, especially in Young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine. on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug Was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4 h (anisomycin), or 8 h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8 h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.