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

在我们的社会中，压力影响着人类和动物的生活。对人类精神健康最不利的是心理压力，例如婚姻问题、工作不安全感和欺凌。在养殖动物和伴侣动物中，心理压力的例子包括过度拥挤（如鸡、猪）、长期运输（如牛、羊、猪）和虐待。成功应对这些压力事件涉及大脑中的适应和认知过程，这些过程使个体在未来对重复的压力更有弹性。然而，有些事件造成的创伤如此之大，以至于对它们的记忆成为巨大的负担，导致身心和行为紊乱以及精神疾病（焦虑和抑郁）。为了帮助人们应对生活中的压力，制定减少压力的指令，改善我们的同伴、农场和实验室动物的健康，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是如何适应压力事件并从中学习的。我们最近发现，在应激后，神经细胞的细胞核中发生了某些分子过程（“表观遗传修饰”），这些过程对于这些细胞适应应激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。获取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。

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.