Exercise Prevents Stress-Induced Memory Impairments

运动可以预防压力引起的记忆障碍

• 批准号: 7893385
• 负责人: BEN N GREENWOOD
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893385
• 关键词: Acute; Address; Adrenergic Receptor; Amnesia; Anxiety; Anxiety Disorders; Behavior Control; Behavioral; Brain-Derived Neurotrophic Factor; Complex; Data; Dependence; Development; Event; Exercise; Exposure to; Failure; Fright; Functional disorder; Goals; Hippocampus (Brain); Human; Incidence; Individual; Laboratories; Lead; Learning; Life; Memory; Memory impairment; Mental Depression; Mental Health; Mental disorders; Neurobiology; Norepinephrine; Phase; Physical activity; Post-Traumatic Stress Disorders; Rattus; Resistance; Running; Severities; Shock; Signal Transduction; Stimulus; Stress; Stressful Event; Symptoms; Testing; Work; base; foot; improved; memory process; novel; novel therapeutics; prevent; protective effect; public health relevance; resilience; stressor

DESCRIPTION (provided by applicant): Stressor exposure is a primary causal factor in the development of psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Stress-related psychiatric disorders are accompanied by disturbances in learning & memory. Individuals with PTSD, for example, can display distorted memory of the traumatic event, including fragmented memory, amnesia, & flashbacks. In addition, PTSD sufferers display generalization of fear &/or sensitization to mild stressors. Although it is clear that stressor exposure can alter learning & memory processes, the mechanisms underlying stress-induced amnesia, generalization, & sensitization remain elusive. Additionally, factors that can provide resilience against the development of stress-related psychiatric disorders including PTSD remain unknown. Physical activity is one behavioral manipulation that can reduce the incidence & severity of anxiety disorders, including PTSD. Voluntary exercise in rats also provides resistance against behavioral effects of stressor exposure & can improve hippocampal- dependent learning & memory processes. The interactions between exercise & stress on learning & memory have, however, yet to be investigated. Rats exposed to an acute, unpredictable stressor, display 1) amnesia of the stressor context, 2) fear generalization, & 3) sensitization to novel stressors. These particular consequences of stressor exposure are dependent on the unpredictability of the stressor, persist for weeks, & resemble long- lasting symptoms of human PTSD. Hippocampal dysfunction could contribute to stress-induced learning & memory impairments by making it difficult to distinguish safe contexts from dangerous ones [1, 2]. Indeed, our preliminary data indicate that stress-induced amnesia can be caused by a disruption in consolidation of the memory of the stressor context that typically occurs in the hippocampus. Additionally, weaker context memories can lead to greater generalization of fear. Six wk of wheel running prevents stress-induced amnesia, perhaps by improving the ability to consolidate the hippocampal-dependent memory of the stressor context. Norepinephrine (NE) & brain-derived neurotrophic factor (BDNF) are 2 factors that could contribute to improved hippocampal-dependent learning & memory following exercise. Wheel running increases NE & BDNF content in the hippocampus & the exercise-induced increase in BDNF occurs via a NE & 2-adrenergic receptor- dependent mechanism. Based on these data, we hypothesize that 1) stress-induced fear generalization & sensitization are dependent on disruption of hippocampal-dependent consolidation of the stressor context & 2) exercise prior to stressor exposure prevents stress-induced amnesia, generalization, & sensitization through a 2-adrenergic receptor-dependent mechanism. PUBLIC HEALTH RELEVANCE: The goal of the current proposal is to investigate the protective effects of physical activity against stress-induced learning and memory impairments, focusing specifically on interactions between the 2 adrenergic receptor, brain-derived neurotrophic factor, and the hippocampus. The results of this work will improve our basic understanding of the effects of stressor exposure on learning and memory processes and the neurobiology of stress-related psychiatric disorders, and could lead to novel therapeutic strategies to prevent or reverse the detrimental consequences of stressor exposure on mental health.

描述（由申请人提供）：压力暴露是抑郁症，焦虑和创伤后应激障碍（PTSD）等精神疾病发展的主要因素。与压力有关的精神疾病伴随着学习和记忆的障碍。例如，患有PTSD的个体可以显示出创伤事件的失真记忆，包括零散的记忆，失忆症和闪回。此外，PTSD患者表现出对轻度压力源的恐惧和/或敏感性的概括。尽管很明显，压力源暴露会改变学习和记忆过程，但压力引起的健忘症，概括和敏化的机制仍然难以捉摸。此外，可以为与压力相关的精神疾病（包括PTSD）的发展提供弹性的因素仍然未知。体育活动是一种行为操纵，可以减少包括PTSD在内的焦虑症的发病率和严重程度。大鼠的自愿运动还提供了抵抗压力源暴露的行为影响，并可以改善海马依赖的学习和记忆过程。但是，尚未研究运动与学习和记忆压力之间的相互作用。 暴露于急性，不可预测的压力源的大鼠表现1）压力源环境的失忆症，2）恐惧概括，＆3）对新型压力源的敏感。压力源暴露的这些特殊后果取决于压力源的不可预测性，持续数周，并且类似于人类PTSD的持续持续症状。海马功能障碍可能会通过使安全环境与危险环境区分开来，从而导致压力引起的学习和记忆障碍[1，2]。实际上，我们的初步数据表明，应力诱导的失忆症可能是由于通常发生在海马中发生的压力源环境记忆的破坏而引起的。此外，弱环境记忆会导致更大的恐惧概括。六周的车轮跑步可以阻止应力引起的失忆症，这可能是通过提高巩固压力源环境中海马依赖性记忆的能力。去甲肾上腺素（NE）和脑衍生的神经营养因子（BDNF）是2个因素，可以在运动后改善海马依赖性学习和记忆。车轮运行会增加海马中的NE＆BDNF含量，而运动引起的BDNF的增加是通过NE＆2-肾上腺素受体依赖的机制发生的。基于这些数据，我们假设1）压力引起的恐惧概括和敏化取决于压力源环境的海马依赖性巩固和2）在压力暴露之前锻炼应激诱导的不稳定性不稳定，概括，概括和通过2-肾上腺素受体依赖性机制进行致敏。 公共卫生相关性：当前建议的目的是研究体育活动对压力引起的学习和记忆障碍的保护作用，专门针对2种肾上腺素能受体，脑源性神经营养因子和海马室之间的相互作用。这项工作的结果将改善我们对压力源对学习和记忆过程的影响以及与压力相关的精神疾病的神经生物学的基本理解，并可能导致新的治疗策略，以防止或扭转压力源对心理健康的有害后果。