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诱导型 cAMP 早期应答元件（ICER）在安非他命诱导的运动敏化中的抑制作用。

Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization.

机构信息

Research Project for Addictive Substances, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

出版信息

PLoS One. 2011;6(6):e21637. doi: 10.1371/journal.pone.0021637. Epub 2011 Jun 28.

DOI:10.1371/journal.pone.0021637
PMID:21738744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3125264/
Abstract

BACKGROUND

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).

METHODS AND FINDINGS

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.

CONCLUSIONS

Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization.

摘要

背景

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，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）作用中的作用。

方法和发现

我们测试了野生型小鼠、ICER 敲除小鼠和 ICER I 过表达小鼠中 METH 诱导的运动敏化作用。连续注射 METH 后，ICER 野生型和敲除型小鼠的运动活性均增加。然而，与野生型小鼠相比，ICER 敲除型小鼠的运动活性有升高的趋势，但两种基因型之间没有观察到显著差异。此外，与野生型小鼠相比，ICER I 过表达小鼠的 METH 诱导运动敏化作用显著降低。此外，Western blot 分析和实时定量反转录聚合酶链反应表明，ICER 过表达消除了 METH 诱导的 CREB 表达增加，并抑制了可卡因和安非他命调节转录物（CART）和前原啡肽（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 抑制 METH 诱导运动敏化的基础。

结论

我们的数据表明，ICER 在 METH 诱导的运动敏化中发挥抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/05607692bf73/pone.0021637.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/1b681433701b/pone.0021637.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/e4d60a66063c/pone.0021637.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/a30b58c6f0ed/pone.0021637.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/05607692bf73/pone.0021637.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/1b681433701b/pone.0021637.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/e4d60a66063c/pone.0021637.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/a30b58c6f0ed/pone.0021637.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d252/3125264/05607692bf73/pone.0021637.g004.jpg

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