DNA methylation regulates the extinction of fear memory.

IF 3.4 4区医学 Q1 PSYCHIATRY

World Journal of Psychiatry Pub Date : 2025-07-19 DOI:10.5498/wjp.v15.i7.107524

Le Jiang, Rui-Xue Ma, Er-Shu He, Xiao-Ye Zheng, Xin Peng, Wen-Hao Ma, Ying Li, Han-Wei Li, Xue-Yan Zhang, Jie-Yu Ji, Yan-Jiao Li, Shang-Lan Qu, Li-Juan Li, Zhi-Ting Gong

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引用次数: 0

Abstract

Background: Fear-related disorders, such as post-traumatic stress disorder (PTSD), significantly impact patients and families. Exposure therapy is a common treatment, but improving its effectiveness remains a key challenge. Fear conditioning and extinction in animal models offer insights into its mechanisms. Our previous research indicates that DNA methyltransferases play a role in fear memory renewal.

Aim: To investigate the role of DNA methylation in the extinction of fear memory, with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.

Methods: This study investigated the role of DNA methylation in fear memory extinction in mice. DNA methylation was manipulated using N-phthalyl-L-tryptophan (RG108) to reduce methylation and L-methionine injections to enhance it. Neuronal activity, and dendritic spine density was measured following extinction training.

Results: RG108 suppressed extinction, reduced spine density, and inhibited neuronal activity. Methionine injections facilitated extinction.

Conclusion: DNA methylation is crucial for fear memory extinction. Enhancing methylation may improve the efficacy of exposure therapy, offering a potential strategy to treat fear-related disorders.

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DNA甲基化调节恐惧记忆的消失。

背景：恐惧相关障碍，如创伤后应激障碍（PTSD），对患者和家庭产生重大影响。暴露疗法是一种常见的治疗方法，但提高其有效性仍然是一个关键的挑战。动物模型中的恐惧调节和灭绝为其机制提供了见解。我们之前的研究表明，DNA甲基转移酶在恐惧记忆更新中起作用。目的：探讨DNA甲基化在恐惧记忆消退中的作用，以确定潜在的策略，以提高暴露疗法对恐惧相关障碍的疗效。方法：研究DNA甲基化在小鼠恐惧记忆消退中的作用。用n -邻苯酞- l-色氨酸（RG108）控制DNA甲基化以降低甲基化，注射l-蛋氨酸以增强甲基化。神经元活动和树突棘密度在消失训练后被测量。结果：RG108抑制了脊髓消失，降低了脊柱密度，抑制了神经元活动。蛋氨酸的注射促进了灭绝。结论：DNA甲基化在恐惧记忆消退过程中起重要作用。增强甲基化可能提高暴露疗法的疗效，为治疗恐惧相关疾病提供了一种潜在的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Psychiatry PSYCHIATRY-

自引率

6.50%

发文量

110

期刊介绍： The World Journal of Psychiatry (WJP) is a high-quality, peer reviewed, open-access journal. The primary task of WJP is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of psychiatry. In order to promote productive academic communication, the peer review process for the WJP is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJP are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in psychiatry.