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Epigenetic control of gene transcriptional and behavioural responses to stress in the dentate gyrus

齿状回应激基因转录和行为反应的表观遗传控制

基本信息

批准号：
BB/K007408/1
负责人：
Johannes Reul
金额：
$ 96.62万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FK007408%2F1
关键词：
Epigenetic control gene transcriptional behavioural

项目摘要

Stress affects the lives of both humans and animals in our society. Most debilitating for mental welfare and wellbeing in humans is psychological stress, for instance marital problems, job insecurity, and bullying. In farmed and companion animals, examples of psychological stress include overcrowding (e.g. chickens, pigs), long-lasting transports (e.g. cows, sheep, pigs) and abuse. Successful coping with such stressful events involves adaptive and cognitive processes in the brain that make the individual more resilient to repeated stress in the future. Some events, however, are so traumatic that the memories of them become a tremendous burden, leading to psychosomatic and behavioural disturbances and psychiatric diseases (anxiety and depression). To help people to cope with stress in their lives, to develop directives to reduce stress and to improve wellbeing of our companion, farmed and laboratory animals, we need to obtain better insight into how the brain processes stress and creates memories of psychologically stressful events. At present it is unclear how the healthy brain adapts to and learns from stressful events. We have recently discovered that after stress certain molecular processes ("epigenetic modifications") occur in the nucleus of nerve cells which are crucial for the expression of genes necessary for the adaptation of these cells to a stressful event. Our proposal aims to investigate the role of these epigenetic modifications in the regulation of gene expression and the identity of the genes affected by these modifications. Obtaining this information is crucial to understand how nerve cells "learn" from stressful events. Insight into these processes and the function of the genes involved will help to develop new ways to reduce the burden of stress-related disorders in humans and animals.

压力影响着我们社会中人类和动物的生活。最削弱人类心理福利和幸福感的是心理压力，例如婚姻问题，工作不安全感和欺凌。在养殖和伴侣动物中，心理压力的例子包括过度拥挤（例如鸡，猪），长期运输（例如牛，羊，猪）和虐待。成功应对这种压力事件涉及大脑中的适应和认知过程，使个体在未来更能适应反复的压力。然而，有些事件的创伤如此之大，以至于对它们的记忆成为巨大的负担，导致心身和行为障碍以及精神疾病（焦虑和抑郁）。为了帮助人们科普生活中的压力，制定减轻压力的指令，改善我们的同伴，饲养和实验室动物的健康状况，我们需要更好地了解大脑如何处理压力并创造心理压力事件的记忆。目前还不清楚健康的大脑如何适应和学习压力事件。我们最近发现，在压力后，某些分子过程（“表观遗传修饰”）发生在神经细胞的细胞核中，这对于这些细胞适应压力事件所必需的基因的表达至关重要。我们的建议旨在研究这些表观遗传修饰在基因表达调控中的作用以及受这些修饰影响的基因的身份。获得这些信息对于理解神经细胞如何从压力事件中“学习”至关重要。深入了解这些过程和相关基因的功能将有助于开发新的方法来减轻人类和动物的压力相关疾病的负担。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain.

DOI：
10.1016/j.ynstr.2023.100532
发表时间：
2023-03
期刊：
NEUROBIOLOGY OF STRESS
影响因子：
5
作者：
Kennedy, Clare L. M.;Price, Emily M.;Mifsud, Karen R.;Salatino, Silvia;Sharma, Eshita;Engledow, Simon;Broxholme, John;Goss, Hannah M.;Reul, Johannes M. H. M.
通讯作者：
Reul, Johannes M. H. M.

Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training.