Are early stress effects on cognitive processes mediated by the mineralocorticoid orglucocorticoid receptor?

早期压力对认知过程的影响是由盐皮质激素或糖皮质激素受体介导的吗？

• 批准号: 396346610
• 负责人: Dr. Christian Deuter
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie (CBF)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/396346610?language=en
• 关键词: early; stress; effects; cognitive; processes

Stress affects several physiological and psychological domains and triggers a shift in information processing that is mediated by two separate neuroendocrine systems: the fast-responding catecholaminergic system and the slower glucocorticoid system. The glucocorticoid system is based on the hypothalamic-pituitary-adrenal axis, with cortisol as the main downstream glucocorticoid in humans. According to the network model of Hermans et al. (2014), two separate brain networks are implicated in the acute stress response. The salience network is responsible for exogenous attention, especially to potential threats, and the fast mobilization of energy. Resources are primarily allocated to this network immediately after the onset of the stressor until about one hour after stress exposure. In this early part of the stress response, the executive control network that mediates deliberate thinking and planned action is down-regulated. This process is initially driven by catecholaminergic activation, which sets in immediately within seconds with stress exposure. In addition and within minutes rapid non-genomic effects of cortisol appear on the scene and start to modulate the catecholaminergic effects. Cortisol can easily cross the blood-brain barrier and feeds back on the brain via two different receptor types: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). While GRs are widely distributed in the brain, MRs are primarily located in limbic structures and the prefrontal cortex, which are areas critical for cognition and emotion. Several human and animal studies indicated a role for membrane-bound MRs in the early phase of the stress response and in rapid cortisol effects on emotional and cognitive processes. However, while rapid stress effects are often attributed to the MR, recent research in animals indicates a role of the - supposedly membrane bound and non-genomic - GR in rapid stress effects as well.These rapid effects are regionally and functionally specific and may differ between MRs and GRs. Overall, effects of GRs rather suppress, and those of MRs rather enhance neural excitability.In the proposed project, we plan to systematically disentangle MR vs. GR effects in the early stress response on emotional and cognitive processes that represent the salience network (attentional vigilance to emotional stimuli as determined by emotional dot-probe), the executive control network (working memory as assessed by n-back task) or both networks (risk taking as assessed by balloon analogue risk task). To our best knowledge, this would be the first project to investigate the differential contribution of both receptor systems on these cognitive domains in such a systematic manner.

应激影响几个生理和心理领域，并引发信息处理的转变，这是由两个独立的神经内分泌系统介导的：快速反应儿茶酚胺系统和较慢的糖皮质激素系统。糖皮质激素系统是以下丘脑-垂体-肾上腺轴为基础的，皮质醇是人类主要的下游糖皮质激素。根据Hermans等人的网络模型。(2014)，两个独立的大脑网络与急性应激反应有关。突显网络负责外部的注意，特别是对潜在威胁的关注，以及快速动员能量。资源主要在应激源开始后立即分配给这个网络，直到压力暴露后大约一个小时。在压力反应的早期阶段，调节刻意思考和有计划的行动的执行控制网络被下调。这个过程最初是由儿茶酚胺能激活驱动的，在压力暴露下，儿茶酚胺能在几秒钟内立即启动。此外，在几分钟内，皮质醇的快速非基因组效应出现在现场，并开始调节儿茶酚胺能效应。皮质醇可以很容易地穿过血脑屏障，并通过两种不同的受体类型反馈到大脑：糖皮质激素受体(GR)和盐皮质激素受体(MR)。虽然GRs广泛分布在大脑中，但MRS主要位于边缘结构和前额叶皮质，这两个区域对认知和情绪至关重要。一些人类和动物的研究表明，膜结合的MRS在应激反应的早期阶段以及在情绪和认知过程中的快速皮质醇效应中发挥了作用。然而，虽然快速应激效应通常归因于MR，但最近在动物中的研究表明，所谓的膜结合和非基因组GR也在快速应激效应中发挥作用。这些快速效应是区域性和功能性的，MRS和GRS可能不同。总体而言，GRs的影响相当抑制，而MRS的影响相当增强神经兴奋性。在拟议的项目中，我们计划系统地区分MR和GR在早期应激反应中对情绪和认知过程的影响，这些情绪和认知过程代表显著网络(由情绪点探测确定的对情绪刺激的注意警戒)、执行控制网络(通过n-back任务评估工作记忆)或两者(通过气球模拟风险任务评估的冒险行为)。据我们所知，这将是第一个以如此系统的方式研究这两个受体系统对这些认知领域的不同贡献的项目。