Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, 19104, USA; Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Trends Neurosci. 2022 Dec;45(12):955-967. doi: 10.1016/j.tins.2022.10.001. Epub 2022 Oct 22.
The dorsal striatum integrates prior and current information to guide appropriate decision-making. Chronic stress and stimulant exposure interferes with decision-making, and can confer similar cognitive and behavioral inflexibilities. This review examines the literature on acute and chronic regulation of the epigenome by stress and stimulants. Recent evidence suggests that exposures to stress and stimulants share similarities in the manners in which they regulate the dorsal striatum epigenome through DNA methylation, transposable element activity, and histone post-translational modifications. These findings suggest that chronic stress and stimulant exposure leads to the accumulation of epigenetic modifications that impair immediate and future neuron function and activity. Such epigenetic mechanisms represent potential therapeutic targets for ameliorating convergent symptoms of stress and addiction.
背侧纹状体整合先前和当前的信息，以指导适当的决策。慢性应激和兴奋剂暴露会干扰决策，并导致类似的认知和行为灵活性障碍。本综述探讨了应激和兴奋剂对表观基因组的急性和慢性调节的文献。最近的证据表明，应激和兴奋剂暴露在通过 DNA 甲基化、转座元件活性和组蛋白翻译后修饰调节背侧纹状体表观基因组的方式上具有相似性。这些发现表明，慢性应激和兴奋剂暴露导致表观遗传修饰的积累，损害即时和未来神经元的功能和活动。这种表观遗传机制代表了改善应激和成瘾的共同症状的潜在治疗靶点。
