The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.
The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion.
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抗代谢物ara-CTP可阻断条件性味觉厌恶的长期记忆。
DOI：
10.1101/lm.63003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
PenadeOrtiz,Sandra
中科院分区：
文献类型：
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作者：
Wang,Jianpeng;Ren,Keqin;Perez,Javier;Silva,AlcinoJ;PenadeOrtiz,Sandra
我们研究了与DNA重组和修复相关的过程参与学习和记忆的假设。在条件性味觉厌恶（CTA）训练前30分钟，大鼠接受侧脑室（icv）注射抗代谢药1-β-D-阿拉伯呋喃糖基胞嘧啶三磷酸（ara-CTP）或其前体阿糖胞苷（ara-C）。ara-CTP和ara-C均导致CTA的长期记忆（LTM）显著受损。对照实验表明，ara-CTP对CTA记忆的影响与干扰学习有关。此外，正如先前证明的蛋白质合成抑制剂茴香霉素，ara-CTP在训练后1小时注射时对CTA记忆没有影响。重要的是，尽管ara-CTP和茴香霉素都显著阻断了任务中的LTM，但训练后1小时测量的短期记忆（STM）不受任何药物的影响。最后，ara-CTP对体外转录没有影响，但它确实有效地阻断了脑蛋白提取物的非同源DNA末端连接（NHEJ）活性。我们认为，DNA连接酶介导的DNA重组和修复过程是必要的LTM在大脑中的表达。
We examined the hypothesis that processes related to DNA recombination and repair are involved in learning and memory. Rats received intracerebroventricular (icv) infusions of the antimetabolite 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) or its precursor cytosine arabinoside (ara-C) 30 min prior to conditioned taste aversion (CTA) training. Both ara-CTP and ara-C caused significant impairments in long-term memory (LTM) of CTA. Control experiments indicate that the effect of ara-CTP on CTA memory is related to interference with learning. Furthermore, as it was previously demonstrated for the protein synthesis inhibitor anisomycin, ara-CTP had no effect on CTA memory when it was injected 1 h after training. Importantly, although both ara-CTP and anisomycin significantly blocked LTM in the task, short-term memory (STM) measured 1 h after training was not affected by either of the drugs. Finally, ara-CTP had no effect on in vitro transcription, but it did effectively block nonhomologous DNA end joining (NHEJ) activity of brain protein extracts. We suggest that DNA ligase-mediated DNA recombination and repair processes are necessary for the expression of LTM in the brain.