Abbas Abdul-Karim, Dozmorov Mikhail, Li Rui, Huang Fen-Sheng, Hellberg Fredrik, Danielson Jonas, Tian Ye, Ekström Jörgen, Sandberg Mats, Wigström Holger
Department of Medical Biophysics, Institute of Neuroscience and Physiology, Gothenburg University, Box 433, 40530 Gothenburg, Sweden.
Neurosci Res. 2009 Jan;63(1):59-65. doi: 10.1016/j.neures.2008.10.008. Epub 2008 Nov 1.
Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h 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 4h (anisomycin), or 8h (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 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
蛋白质合成被认为参与稳定突触可塑性。持续时间超过约2 - 3小时的效应被认为需要合成新的蛋白质，这意味着早期（E）和晚期（L）成分之间存在功能分离。然而，组成型蛋白质合成与新蛋白质合成的问题仍不明确，尤其是在幼小动物中。在这里，我们研究了两种蛋白质合成抑制剂茴香霉素和吐根碱对12至20日龄大鼠海马切片CA1区长期增强（LTP）的影响。相对于LTP诱导，在-30分钟至+30分钟的时间窗口内应用任何一种药物，该时间窗口先前已报道是关键的。然而，在4小时（茴香霉素）或8小时（吐根碱）的整个记录期内，LTP保持稳定。吐根碱溶液的正确配制通过以下事实得到证明：在单独的实验中，用吐根碱进行长时间处理会逐渐阻断基线反应。尽管用茴香霉素未观察到相应的效果，但根据其抑制酵母生长的能力判断该药物是有效的。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茴香霉素抑制蛋白质合成的能力。我们的数据表明，至少长达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有的蛋白质来实现。
