Rewarding experience and the aging brain

奖励经验和老化的大脑

• 批准号: 7928263
• 负责人: Erica R Glasper
• 金额: $ 5.58万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928263
• 关键词: Acute; Address; Adult; Affect; Age; Aging; Animals; Architecture; Brain; Bromodeoxyuridine; Chronic; Cognition; Cognitive deficits; Dendritic Spines; Diet; Eating; Elderly; Environment; Environmental Risk Factor; Excitatory Synapse; Exercise; Exposure to; Fatty acid glycerol esters; Genetic; Glucocorticoids; Golgi Apparatus; Hippocampus (Brain); Hormones; Immunofluorescence Immunologic; Impaired cognition; Individual Differences; Knowledge; Label; Lead; Learning; Life Expectancy; Mammals; Measures; Mediating; Medicine; Memory; Nature; Neurons; Performance; Plastics; Play; Predisposition; Primates; Reporting; Research Design; Resistance; Rewards; Rodent; Role; Running; Science; Sex Behavior; Shock; Site; Social Interaction; Social isolation; Staging; Staining method; Stains; Stress; Structure; Swimming; Synapses; Time; Vertebral column; Well in self; adult neurogenesis; age related; aged; aging brain; aging hippocampus; cognitive function; conditioned fear; density; design; experience; male; mature animal; middle age; morris water maze; neurogenesis; prenatal stress; prevent; public health relevance; relating to nervous system; research study; senescence; social; way finding; young adult

DESCRIPTION (provided by candidate): Aging is associated with a decline in cognitive function that begins in midlife. Age-associated deficits in learning and memory are often accompanied by impaired synaptic and structural plasticity in the hippocampus, including diminished adult neurogenesis. Individual differences in the rate of cognitive decline with aging are probably due to the combined influence of genetic and environmental factors. Indeed, experience has been shown to alter both cognitive function and hippocampal plasticity in adulthood. Exposures to aversive experiences, such as shock, cold swim, and predator exposure, negatively affect hippocampal structure, at least in part by elevating stress hormones. Compared to those of a negative nature, positive experiences involve a rewarding or motivating component-examples including running, eating a high fat diet, and sexual behavior. Each of these experiences activates the HPA axis. Evidence suggests that sexual experience paradoxically increases both glucocorticoids and adult neurogenesis in the young adult hippocampus, but no studies have examined its effects on the aging brain. To investigate the influence of a rewarding social experience on the aging brain, the following specific aims will be addressed: 1) to determine whether sexual experience reverses age-associated changes in adult neurogenesis and 7 dendritic architecture, and 2) to determine whether sexual experience mitigates age-associated cognitive deficits. These specific aims will explore the interrelationships among rewarding experience, aging, hippocampal structure, and learning by comparing the effects of acute and chronic sexual experience on the following: adult neurogenesis, using BrdU labeling and immunofluorescence; dendritic spines, using Dil and Golgi staining; spatial navigation ability using the Morris water maze. These studies are designed to fill the gaps in our current knowledge and potentially lead to understanding the mechanisms underlying predisposition and resistance to age-induced deficits in neurogenesis and cognitive decline. PUBLIC HEALTH RELEVANCE: the mean life expectancy is extended due to advances in modern science and medicine, many concerns regarding the physical and mental well-being of the aged have been raised. Age- induced alterations in structural plasticity (i.e., neurogenesis, spine density) in the hippocampus may be involved in the functional abnormalities associated with cognitive decline, with experiences possibly ameliorating these effects. The studies outlined in this proposal are designed to fill the gaps in our knowledge surrounding these topics, with a view toward understanding the mechanisms underlying predisposition and resistance to age-induced deficits in structural plasticity and cognitive decline.

描述（由考生提供）：衰老与从中年开始的认知功能下降有关。与年龄相关的学习和记忆缺陷通常伴随着海马突触和结构可塑性受损，包括成人神经发生的减少。随着年龄增长认知能力下降速度的个体差异可能是由于遗传和环境因素的综合影响。事实上，经验已被证明可以改变成年后的认知功能和海马可塑性。暴露于令人厌恶的经历，如电击、冷水游泳和捕食者暴露，会对海马结构产生负面影响，至少部分是通过升高应激激素来影响。与消极的经历相比，积极的经历涉及奖励或激励成分，例如跑步、高脂肪饮食和性行为。这些经历中的每一种都会激活 HPA 轴。有证据表明，性经历反而会增加年轻成年海马体中的糖皮质激素和成人神经发生，但没有研究检验其对衰老大脑的影响。为了研究有益的社会经历对衰老大脑的影响，将解决以下具体目标：1）确定性经历是否逆转成人神经发生和7树突结构中与年龄相关的变化，2）确定性经历是否减轻与年龄相关的认知缺陷。这些具体目标将通过比较急性和慢性性体验对以下方面的影响，探索奖励性体验、衰老、海马结构和学习之间的相互关系：成人神经发生，使用 BrdU 标记和免疫荧光；树突棘，使用 Dil 和高尔基染色；使用莫里斯水迷宫的空间导航能力。这些研究旨在填补我们当前知识的空白，并有可能帮助人们理解年龄引起的神经发生和认知衰退缺陷的易感性和抵抗力的机制。公共健康相关性：由于现代科学和医学的进步，平均预期寿命得到延长，人们对老年人的身心健康提出了许多担忧。年龄引起的海马结构可塑性（即神经发生、脊柱密度）的改变可能与认知能力下降相关的功能异常有关，而经历可能会改善这些影响。本提案中概述的研究旨在填补我们围绕这些主题的知识空白，以期了解年龄引起的结构可塑性和认知衰退缺陷的易感性和抵抗力的潜在机制。

项目成果

Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

性体验增强了内侧前额叶皮层的认知灵活性和树突棘密度。

• DOI: 10.1016/j.nlm.2015.07.007
• 发表时间: 2015
• 期刊: Neurobiology of learning and memory
• 影响因子: 2.7
• 作者: Glasper,EricaR;LaMarca,ElizabethA;Bocarsly,MiriamE;Fasolino,Maria;Opendak,Maya;Gould,Elizabeth
• 通讯作者: Gould,Elizabeth