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创伤性脑损伤的表观遗传机制。

Epigenetic Mechanisms of Traumatic Brain Injuries.

机构信息

Savitribai Phule Pune University, Pune, Maharashtra, India.

Savitribai Phule Pune University, Pune, Maharashtra, India.

出版信息

Prog Mol Biol Transl Sci. 2018;157:263-298. doi: 10.1016/bs.pmbts.2017.12.013. Epub 2018 Apr 11.

DOI:10.1016/bs.pmbts.2017.12.013
PMID:29933953
Abstract

Of all types of injuries, traumatic brain injuries (TBIs) are most likely to result in death or permanent physical or mental disabilities. With the increased frequency of military operations, terror attacks, sports activities, and road mishaps, TBIs are increasingly becoming a serious public health concern. Patients who meet with moderate-to-severe TBI suffer from a constellation of cognitive deficits and phenotypes due to diffuse axonal injury. On the contrary, minimal TBI precipitates in long-term behavioral complications commonly referred to as post-traumatic stress disorders, which consist of depression, anxiety, hallucinations, and so on. During the last decade, epigenetic mechanisms, such as histone posttranslational modifications, DNA methylation, and noncoding RNAs, have received reasonable attention by scientists studying the neurobiology of TBI. Chromatin remodeling sculpted by various epigenetic factors in different parts of the brain controls many intricate processes involved in important neural functions. Although stable and dogmatic, the reversible nature of epigenetic modifications has attracted special attention for their emerging potential in therapeutic development. Herein, we offer an overview of recent observations on epigenetic pathways that are likely involved in shaping neural function and maintain the state of neuropathology in response to traumatic events.

摘要

在所有类型的损伤中,创伤性脑损伤(TBI)最有可能导致死亡或永久性身体或精神残疾。随着军事行动、恐怖袭击、体育活动和道路事故的频率增加,TBI 越来越成为一个严重的公共卫生问题。中度至重度 TBI 患者由于弥漫性轴索损伤而患有一系列认知缺陷和表型。相反,轻度 TBI 会引发长期的行为并发症,通常称为创伤后应激障碍,包括抑郁、焦虑、幻觉等。在过去十年中,表观遗传机制,如组蛋白翻译后修饰、DNA 甲基化和非编码 RNA,受到了研究 TBI 神经生物学的科学家的合理关注。不同大脑部位的各种表观遗传因素重塑的染色质重塑控制着许多涉及重要神经功能的复杂过程。尽管表观遗传修饰是稳定和教条的,但由于其在治疗开发中的新兴潜力,其可逆性引起了特别关注。本文概述了最近关于可能参与塑造神经功能并维持神经病理学状态以应对创伤性事件的表观遗传途径的观察结果。

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