Sex differences in factors influencing cognitive aging

影响认知衰老因素的性别差异

• 批准号: 6906282
• 负责人: HEATHER A. BIMONTE-NELSON
• 金额: $ 6.13万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6906282
• 关键词: age difference; animal old age; behavior test; behavioral /social science research tag; cognition; dietary lipid; estrogens; experience; gender difference; hormone regulation /control mechanism; juvenile animal; laboratory rat; mature animal; memory; neurotrophic factors; nutrition related tag; pathogenic diet; psychological aspect of aging; testosterone

DESCRIPTION (provided by applicant): There is increasing evidence that behavioral and hormonal factors alter progression of aging and Alzheimer's Disease (AD). Such knowledge has great implications for strategies to prevent cognitive decline. The rodent model will be used to evaluate two factors that human research suggests alter age- and disease- related changes: prior cognitive experience and a high fat diet. 1) Prior cognitive experience: Does using it prevent you from losing it? People who stay mentally active show less age-related cognitive decline. Animal work addressing this has only used males, and the limitations of cognitive practice have not been detailed. One male and one female group will receive no maze testing, while another will receive only procedural components of testing. The other male and female rats will receive either working or reference memory cognitive practice throughout life, and then spatial and non-spatial working and reference memory testing when they become aged to evaluate whether memory transfer effects occur. Also, we recently found that both-cognitive testing and aging altered neurotrophins. We hypothesize that these alterations due to cognitive testing protect against age-related memory decline. Specific Aim 1 tests the hypothesis that the mnemonic demands of cognitive practice affect whether cognitive practice procedures attenuate age-related neurotrophin and cognitive changes. 2) High fat/cholesterol (HF/HQ diet: Data suggest that a HF/HC diet is a risk factor for cognitive decline in aging and AD. We found that a HF/HC diet impaired memory in middle-aged male rats, and that testosterone treatment improved memory in aged male rats. Since human work found that testosterone treatment improved cognition and lipid profiles in older men, we question whether testosterone reverses the detrimental effects of a HF/HC diet. All animal studies testing effects of a high fat diet used young or middle-aged males. Since data suggest that males are more sensitive to adverse dietary conditions, we will evaluate the effects of a HF/HC diet in middle-aged males vs. females. In women, data suggest that menopause status affects cardiovascular risk factors such as lipid profiles. Middle-aged female rats can be grouped into state of "menopause" (estropause), which affords us the opportunity to evaluate interactions between reproductive senescence, HF/HC diet, and cognition. We will ovariectomize one group of middle-aged females, and divide intact females into estropause state to determine if ovarian hormone removal or reproductive senescence influences cognitive outcome of a HF/HC diet. Specific Aim 2 tests the hypotheses that middle-aged females, like males, show cognitive impairment due to a HF/HC diet depending on state of estropause, and that testosterone attenuates the detrimental effects of a HF/HC diet in middle-aged males. After the maze battery, rats from both studies will have neurotrophin levels assayed in cognitive brain regions.

描述（由申请人提供）： 越来越多的证据表明，行为和激素因素改变了衰老和阿尔茨海默氏病的进展（AD）。这种知识对预防认知能力下降的策略具有很大的影响。啮齿动物模型将用于评估人类研究表明的两个因素改变年龄和疾病与疾病相关的变化：先前的认知经验和高脂肪饮食。 1）先前的认知经验：使用它是否阻止您失去它？保持精神活跃的人表现出与年龄相关的认知能力下降。解决此问题的动物工作仅使用了男性，并且尚未详细介绍认知实践的局限性。一个男性和一个女性将不会接受迷宫测试，而另一个女性将仅接受测试的程序组成部分。其他雄性和雌性大鼠将在一生中获得工作或参考记忆认知实践，然后在老化时进行空间和非空间工作和参考记忆测试，以评估是否发生记忆转移效应。另外，我们最近发现，认知测试和衰老改变了神经营养蛋白。我们假设由于认知测试而引起的这些改变可以防止与年龄相关的记忆下降。具体目标1检验了以下假设：认知实践的助记符需求会影响认知实践程序是否减弱与年龄相关的神经营养蛋白和认知变化。 2) High fat/cholesterol (HF/HQ diet: Data suggest that a HF/HC diet is a risk factor for cognitive decline in aging and AD. We found that a HF/HC diet impaired memory in middle-aged male rats, and that testosterone treatment improved memory in aged male rats. Since human work found that testosterone treatment improved cognition and lipid profiles in older men, we question whether testosterone reverses the detrimental effects HF/HC饮食的所有动物研究都使用了年轻的或中年的男性。 （雌雄同物）为我们提供了评估生殖衰老，HF/HC饮食和认知之间的相互作用的机会。具体目标2检验了中年女性（如雄性）的假设，由于HF/HC饮食而取决于雌类的状态，因此表现出认知障碍，并且睾丸激素减弱了HF/HC饮食对中年男性的有害作用。迷宫电池后，两项研究的大鼠将在认知大脑区域中测定神经营养蛋白水平。