Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization.
Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization.
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DOI：
10.1371/journal.pone.0021637
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Han W;Takamatsu Y;Yamamoto H;Kasai S;Endo S;Shirao T;Kojima N;Ikeda K
诱导型环磷酸腺苷（cAMP）早期阻遏物（ICER）在中枢神经系统中高度表达，并作为cAMP反应元件结合蛋白（CREB）转录的阻遏物发挥作用。本研究旨在阐明ICER在甲基苯丙胺（METH）效应中的作用。我们在野生型小鼠、ICER敲除小鼠和ICER I过表达小鼠中测试了MET诱导的运动致敏性。ICER野生型小鼠和基因敲除小鼠在连续注射METH后均表现出运动活性增加。然而，ICER基因敲除小鼠表现出更高的自发活动与野生型小鼠相比，虽然没有显着差异，观察到两种基因型。此外，与野生型小鼠相比，ICER I过表达小鼠表现出显着降低在METH-induced自发敏化。此外，Western印迹分析和定量实时逆转录聚合酶链反应表明，ICER过表达废除了甲基诱导的CREB表达的增加，并抑制可卡因和安非他明调节的转录本（CART）和强啡肽原（Pdyn）在小鼠中的表达。体内CART和Pdyn mRNA表达水平的降低可能是ICER在MET诱导的运动敏化中的抑制作用的基础。我们的数据表明，ICER起着抑制作用的甲基诱导的运动敏化。
The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH). We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization. Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization.
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影响因子：
5.3
作者：
Kreibich, AS;Blendy, JA
通讯作者：
Blendy, JA
DOI：
10.1124/jpet.105.091678
发表时间：
2005-12-01
影响因子：
3.5
作者：
Couceyro, PR;Evans, C;Bannon, AW
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影响因子：
4.7
作者：
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通讯作者：
Kuhar, MJ
DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
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通讯作者：
Nestler, EJ
影响因子：
5.3
作者：
Kojima, Nobuhiko;Borlikova, Gilyana;Endo, Shogo
通讯作者：
Endo, Shogo