Interactive effects of short-term estrogen replacement and long-term exercise on the aging brain and cognition in a rodent model of menopause

短期雌激素替代和长期运动对更年期啮齿动物模型衰老大脑和认知的相互作用

• 批准号: 9298789
• 负责人: Shaefali Pillai Rodgers
• 金额: $ 21.63万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9298789
• 关键词: Adjuvant; Adverse effects; Aerobic Exercise; Affect; Aftercare; Age; Aging; Alzheimer' s Disease; Attention; Behavior assessment; Brain; Brain region; Brain-Derived Neurotrophic Factor; Cardiovascular system; Climacteric; Clinical; Cognition; Cognitive; Combined Modality Therapy; Complementary therapies; Costs and Benefits; Deterioration; Development; Environment; Estrogen Receptor alpha; Estrogen Replacement Therapy; Estrogen Replacements; Estrogen Therapy; Estrogens; Exercise; Exposure to; Female; Health; Hippocampus (Brain); Hormone replacement therapy; Hormones; Impaired cognition; Impairment; Insulin-Like Growth Factor I; Intervention; Investigation; Knowledge; Learning; Long-Term Effects; Mediating; Menopause; Modeling; Molecular Target; Neurobiology; Neurologic; Operative Surgical Procedures; Osteoporotic; Outcome; Ovarian; Ovarian hormone; Ovariectomy; Performance; Physiological; Post-Menopausal Hormone Replacement Therapy; Postmenopause; Prefrontal Cortex; Process; Public Health; Rattus; Reporting; Risk; Rodent Model; Severities; Short-Term Memory; Signal Pathway; Synaptic plasticity; Testing; Therapeutic; Up-Regulation; Woman; aging brain; animal tissue; anxiety-like behavior; associated symptom; brain health; brain tissue; cancer risk; cognitive function; cognitive recovery; cost; cost effective; deprivation; executive function; experimental study; fitness; healthy aging; hormone therapy; improved; insight; interest; killings; malignant breast neoplasm; memory recognition; men; middle age; mortality; neurobiological mechanism; neurogenesis; neuroprotection; older women; pre-clinical; prevent; receptor; sedentary; treatment duration; treatment strategy

Women are at an increased risk for cognitive decline after natural or surgical menopause due to the permanent loss of ovarian hormones. Hormone replacement therapy, which is typically prescribed for climacteric symptoms associated with menopause, can also provide some cognitive benefits. However, the adverse side effects of long-term treatment prevent its prolonged use. Few investigations to date have looked at the long-term impact of hormone replacement after treatment has been discontinued. We have developed a middle-aged rodent model of short-term estrogen replacement therapy which is as effective as long-term, continuous treatment at improving spatial working memory. It also induces sustained upregulation of its cognate alpha- receptor, in the hippocampus, a region of the brain required for spatial working memory. While hippocampal function can benefit from estrogen treatment, other cognitive domains may be adversely affected or remain unaffected. Thus, we propose to examine the utility of our model in protecting prefrontal cortical function, which is particularly susceptible to deterioration during advanced aging and can be unaffected or worse, impaired, by prolonged estrogen exposure. Given that estrogen therapy can have opposing effects in a brain region-specific manner and the risks associated with extended use, it is imperative that we develop adjuvant or alternative therapeutic strategies. Aerobic exercise is an obvious candidate because it has general health and cognitive benefits, is neuroprotective during aging, and is a cost-free nonpharmacological intervention. Our main objective, therefore, is to demonstrate the capacity for these two therapies to be used in combination to promote healthy aging post menopause. We expect combination therapy to be maximally beneficial for physiological and brain health. Moreover, evaluating the effects of the two strategies on brain plasticity, alone and in combination, will provide valuable insight into the divergence and overlap in their underlying mechanisms of action.

女性在自然或手术绝经后认知能力下降的风险增加，因为永久性的