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，行为和激素因素会改变衰老和阿尔茨海默病 (AD) 的进展。这些知识对于预防认知能力下降的策略具有重大意义。啮齿动物模型将用于评估人类研究表明改变年龄和疾病相关变化的两个因素：先前的认知经验和高脂肪饮食。 1）先前的认知经验：使用它是否可以防止你失去它？保持精神活跃的人与年龄相关的认知能力下降较少。解决这一问题的动物工作仅使用雄性，并且认知实践的局限性尚未详细说明。一组男性和一组女性将不接受迷宫测试，而另一组将仅接受测试的程序部分。其他雄性和雌性大鼠将在一生中接受工作或参考记忆认知练习，然后在它们变老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。此外，我们最近发现认知测试和衰老都会改变神经营养素。我们假设认知测试引起的这些改变可以防止与年龄相关的记忆衰退。具体目标 1 检验了以下假设：认知练习的助记要求会影响认知练习程序是否会减弱与年龄相关的神经营养素和认知变化。 2）高脂肪/胆固醇（HF/HQ饮食）：数据表明HF/HC饮食是衰老和AD认知能力下降的危险因素。我们发现HF/HC饮食损害中年雄性大鼠的记忆力，并且由于人类研究发现睾酮治疗改善了老年男性的认知和血脂状况，因此我们质疑睾酮是否可以逆转 HF/HC 饮食的有害影响。由于数据表明男性对不良饮食条件更敏感，因此我们将评估 HF/HC 饮食对中年男性与女性的影响，数据表明：更年期状态影响心血管危险因素，例如血脂状况，中年雌性大鼠可分为“更年期”（雌性绝经）状态，这使我们有机会评估生殖衰老、HF/HC 饮食和心血管疾病之间的相互作用。我们将切除一组中年女性的卵巢，并将未绝育的女性分为绝经期状态，以确定卵巢激素去除或生殖衰老是否会影响 HF/HC 饮食的认知结果。具体目标 2 测试了这样的假设：中年女性与男性一样，会因 HF/HC 饮食而出现认知障碍（具体取决于绝经期状态），并且睾酮会减弱 HF/HC 饮食对中年男性的有害影响。迷宫电池后，这两项研究的老鼠将在认知大脑区域检测神经营养素水平。