HORMONE EFFECTS ON MEMORY AND NEUROBIOLOGY IN AGING MICE

激素对衰老小鼠记忆和神经生物学的影响

• 批准号: 2865456
• 负责人: Karyn M Frick
• 金额: $ 3.84万
• 依托单位: WELLESLEY COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2865456
• 关键词: age difference; aging; brain; cervical /vaginal smear; estradiol; estrus; gender difference; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; laboratory mouse; memory; neurobiology; neuroendocrine system; nonhuman therapy evaluation; ovariectomy; progesterone; radioimmunoassay; synapses

DESCRIPTION Age-related spatial memory decline occurs earlier in female mice relative to males. Although this sex difference coincides with the age- related cessation of regular estrous cycling (at 17 months of age), levels of ovarian hormones have been directly measure din the context of memory decline in aging. Therefore, it is unknown whether loss of these hormones contributes to sex differences in spatial memory decline. The proposed studies re designed to determine: 1) the age at which sex differences in spatial memory begin to emerge, 2) whether the onset of these six differences is related to age-related ovarian hormone decline, 3) whether neuroanatomical markers that are affected by age and ovarian hormones differentially decline in males and females, and 4) whether treatment of middle-aged females with hormone replacement will ameliorate their spatial memory deficit. In Experiment 1, designed to address questions 1-3, the spatial memory of male and female mice at 4 ages (5, 11, 14, and 17 months) will be measured in a 1-day water maze tasks, immediately after which the mice will be perfused and their brains removed for measurement of synapse and cholinergic neuron number. Blood will be collected for measurement of ovarian hormone levels. In Experiment 2, which will address question 4, ovariectomized 17 month-old female mice will be given hormone replacement and their spatial memory will be tested as in Experiment 1. The results of this study will provide insights into the mechanisms of, and possible treatments for, cognitive decline in menopausal women.

描述 与空间记忆相关的衰退在雌性小鼠中发生得更早 相对于男性。尽管这种性别差异与年龄一致- 与正常发情周期的停止有关（17月龄时）， 卵巢激素的水平已经在以下情况下被直接测量： 记忆力衰退因此，不知道这些损失是否 激素导致空间记忆下降的性别差异。的 拟议的研究重新设计，以确定：1）年龄， 空间记忆的差异开始出现，2）是否开始 这六个差异与年龄相关的卵巢激素下降有关， 3)受年龄和卵巢影响的神经解剖学标志物 激素在男性和女性中不同程度地下降，以及4）是否 用激素替代治疗中年女性， 改善他们的空间记忆缺陷。在实验1中， 回答问题1-3，4岁时雄性和雌性小鼠的空间记忆 将在1天水迷宫中测量年龄（5、11、14和17个月） 任务，之后立即对小鼠进行灌注， 取出脑以测量突触和胆碱能神经元数量。 将采集血液用于测量卵巢激素水平。在 实验2，将解决问题4，卵巢切除17个月大 雌性小鼠将被给予激素替代， 将如实验1中那样进行测试。这项研究的结果将 提供了深入了解的机制，和可能的治疗方法， 更年期妇女认知能力下降。