MeCP2 Expression in a Rat Model of Risky Decision Making
MeCP2 Expression in a Rat Model of Risky Decision Making
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DOI：
10.1016/j.neuroscience.2017.11.016
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发表时间：
2018-01-15
期刊：
影响因子：
3.3
通讯作者：
Setlow, Barry
中科院分区：
文献类型：
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作者：
Deng, Jay V.;Orsini, Caitlin A.;Setlow, Barry
许多神经精神障碍与涉及惩罚风险的异常决策有关，但其潜在的分子基础仍然知之甚少。甲基CpG结合蛋白2（MeCP2）是一种表观遗传因子，通过直接结合甲基化DNA来调节转录。在这里，我们评估了MeCP2表达的风险承担行为的背景下，使用风险决策任务（RDT），其中大鼠之间的一个小的“安全”的食物奖励和一个大的“风险”的食物奖励伴随着不同的惩罚概率离散的选择。在实验1中，MeCP2的表达，通过免疫印迹评估在内侧前额叶皮层（mPFC），但不是纹状体，与最后一次RDT测试后7天的大，风险奖励（冒险）的偏好程度呈负相关。在实验2中，MeCP2表达90分钟后RDT测试，使用免疫组织化学评估，抑制在背侧mPFC（dmPFC）和延髓核相比，家庭笼控制，表明MeCP2表达调节RDT性能。另外的实验表明，RDT的表现增加了在dmPFC主神经元中Ser421磷酸化的MeCP2的表达（与神经元活性和基因表达的激活相关）。最后，在实验1中，在腹侧mPFC中MeCP2的较低表达与基线条件下更大的风险承担相关。总之，这些发现表明MeCP2在风险决策中的复杂调节作用，并表明表观遗传因素可能是这种决策过程的分子机制的重要组成部分。(C)2017年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Many neuropsychiatric disorders are associated with abnormal decision making involving risk of punishment, but the underlying molecular basis remains poorly understood. Methyl CpG-binding protein 2 (MeCP2) is an epigenetic factor that regulates transcription by directly binding to methylated DNA. Here, we evaluated MeCP2 expression in the context of risk-taking behaviors using the Risky Decision-making Task (RDT), in which rats make discrete choices between a small "safe" food reward and a large "risky" food reward accompanied by varying probabilities of punishment. In Experiment 1, expression of MeCP2 as assessed by immunoblotting in the medial prefrontal cortex (mPFC), but not the striatum, was inversely correlated with the degree of preference for the large, risky reward (risk taking) seven days after the last RDT test. In Experiment 2, MeCP2 expression 90 min after RDT testing, assessed using immunohistochemistry, was suppressed in both the dorsal mPFC (dmPFC) and nucleus accumbens compared to home cage controls, indicating that MeCP2 expression is modulated by RDT performance. Additional experiments revealed that RDT performance increased expression of MeCP2 phosphorylated at Ser421 (associated with neuronal activity and activation of gene expression) in dmPFC principal neurons. Finally, as in Experiment 1, lower expression of MeCP2 in the ventral mPFC was associated with greater risk taking under baseline conditions. Together, these findings indicate a complex regulatory role of MeCP2 in risky decision making, and suggest that epigenetic factors may be an important component of the molecular mechanisms underlying such decision-making processes. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.