Rewarding experience and the aging brain

描述（由候选人提供）：衰老与中年开始的认知功能下降有关。海马体相关的学习和记忆缺陷通常伴随着海马体中突触和结构可塑性受损，包括成年神经发生减少。随着年龄的增长，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，经验已经被证明可以改变成年人的认知功能和海马体的可塑性。暴露于令人厌恶的经历，如休克、冷水游泳和捕食者暴露，对海马结构产生负面影响，至少部分是通过升高应激激素。与那些消极的体验相比，积极的体验包括奖励或激励成分，例如跑步、吃高脂肪食物和性行为。每一种经历都会激活HPA轴。有证据表明，性经验矛盾地增加了年轻成人海马体中的糖皮质激素和成人神经发生，但没有研究研究过它对衰老大脑的影响。为了研究有益的社会经验对衰老大脑的影响，将解决以下具体目标：1）确定性经验是否逆转成人神经发生和树突结构中与年龄相关的变化，以及2）确定性经验是否减轻与年龄相关的认知缺陷。这些具体的目标将探讨奖励经验，老龄化，海马结构和学习之间的相互关系，通过比较急性和慢性性经验对以下方面的影响：成人神经发生，使用BrdU标记和免疫荧光;树突棘，使用Dil和高尔基体染色;空间导航能力，使用Morris水迷宫。这些研究旨在填补我们目前知识的空白，并可能导致理解易感性和抵抗年龄诱导的神经发生和认知能力下降的机制。公共卫生相关性：由于现代科学和医学的进步，平均预期寿命延长，人们对老年人的身心健康提出了许多关切。年龄诱导的结构可塑性改变（即，海马中的神经发生、棘密度）可能参与与认知下降相关的功能异常，经历可能改善这些影响。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，以期了解结构可塑性和认知衰退中年龄诱导缺陷的易感性和抵抗力的机制。

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.