卵巢早衰会导致与阿尔茨海默病相关的大脑改变，而高强度间歇训练无法使小鼠的这些改变恢复。
Accelerated ovarian failure results in brain alterations related to Alzheimer's disease that are not recovered by high-intensity interval training in mice.
作者信息
Mohammad Ahmad, Finch Michael S, Rouhana Sarah, Mashouri Parastoo, Barry Ciara, Hubbard Emma F, Sze Newman, Beaudette Shawn M, Pyle W Glen, Power Geoffrey A, MacPherson Rebecca E K
机构信息
Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
IMPART Team Canada, Dalhousie Medicine, Dalhousie University, Saint John, New Brunswick, Canada.
出版信息
Alzheimers Dement. 2025 Feb;21(2):e14463. doi: 10.1002/alz.14463. Epub 2024 Dec 23.
INTRODUCTION
The menopausal decline in ovarian estrogen production is thought to increase the risk of Alzheimer's disease; however, this link requires further investigation. The chronological development of this connection is not well defined because of the lack of animal models that recapitulate the time course of menopause. This study characterized the cognitive and neuronal effects of the 4-vinylcyclohexene diepoxide (VCD) model of ovarian failure in female mice and assessed whether high-intensity interval training (HIIT) would attenuate impairments.
METHODS
Female mice were injected with VCD for 15 days. Novel object recognition tests (NORT) were conducted during (perimenopause) and after (menopause) ovarian failure (n = 7). HIIT was initiated in menopause and mice underwent NORT testing after 2 and 8 weeks of HIIT (n = 5).
RESULTS
VCD mice had a lower discrimination index, and lower SNAP25 and NeuN expression in perimenopause. HIIT did not recover memory in VCD mice.
DISCUSSION
Neuronal changes arise early in the perimenopausal transition and HIIT did not improve recognition memory when initiated in menopause.
HIGHLIGHTS
The menopausal decline in ovarian estrogen production increases the risk of Alzheimer's disease (AD). The chronological development of this connection is not well defined because of the lack of animal models that recapitulate the time course of menopause. 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure provides a model that simulates the average human experience in the transition from perimenopause to menopause. We demonstrate that cognitive and biochemical effects related to AD pathology are present from the earliest available timepoint in perimenopause in VCD mice. This work highlights the importance of examining the time course in the progression to menopause and the use of VCD as a model to investigate changes in the brain.
引言
卵巢雌激素分泌的绝经后减少被认为会增加患阿尔茨海默病的风险；然而，这种联系需要进一步研究。由于缺乏能够重现绝经时间进程的动物模型，这种联系的时间发展尚不明确。本研究描述了4-乙烯基环己烯二环氧化物（VCD）诱导的雌性小鼠卵巢功能衰竭的认知和神经元效应，并评估了高强度间歇训练（HIIT）是否会减轻损伤。
方法
雌性小鼠注射VCD 15天。在卵巢功能衰竭期间（围绝经期）和之后（绝经后）进行新物体识别测试（NORT）（n = 7）。HIIT在绝经后开始，小鼠在HIIT进行2周和8周后接受NORT测试（n = 5）。
结果
VCD小鼠在围绝经期的辨别指数较低，SNAP25和NeuN表达也较低。HIIT并未恢复VCD小鼠的记忆。
讨论
神经元变化在围绝经期过渡早期就已出现，且HIIT在绝经后开始时并不能改善识别记忆。
重点
卵巢雌激素分泌的绝经后减少会增加患阿尔茨海默病（AD）的风险。由于缺乏能够重现绝经时间进程的动物模型，这种联系的时间发展尚不明确。4-乙烯基环己烯二环氧化物（VCD）诱导的卵巢功能衰竭提供了一个模型，模拟了人类从围绝经期到绝经的平均经历。我们证明，与AD病理学相关的认知和生化效应在VCD小鼠围绝经期最早的时间点就已存在。这项工作强调了研究绝经进展时间进程以及使用VCD作为模型来研究大脑变化的重要性。
Zotero 插件