Vrontou Sophia, Bédécarrats Alexis, Wei Xiaofei, Ayodeji Morikeoluwa, Brassai Attila, Molnár László, Mody Istvan
Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
The Peddie School, Hightstown, NJ 08520, USA.
Brain Commun. 2022 Jun 22;4(4):fcac166. doi: 10.1093/braincomms/fcac166. eCollection 2022.
To date, potential mechanisms of menopause-related memory and cognitive deficits have not been elucidated. Therefore, we studied brain oscillations, their phase-amplitude coupling, sleep and vigilance state patterns, running wheel use and other behavioural measures in a translationally valid mouse model of menopause, the 4-vinylcyclohexene-diepoxide-induced accelerated ovarian failure. After accelerated ovarian failure, female mice show significant alterations in brain rhythms, including changes in the frequencies of θ (5-12 Hz) and γ (30-120 Hz) oscillations, a reversed phase-amplitude coupling, altered coupling of hippocampal sharp-wave ripples to medial prefrontal cortical sleep spindles and reduced δ oscillation (0.5-4 Hz) synchrony between the two regions during non-rapid eye movement sleep. In addition, we report on significant circadian variations in the frequencies of θ and γ oscillations, and massive synchronous δ oscillations during wheel running. Our results reveal novel and specific network alterations and feasible signs for diminished brain connectivity in the accelerated ovarian failure mouse model of menopause. Taken together, our results may have identified changes possibly responsible for some of the memory and cognitive deficits previously described in this model. Corresponding future studies in menopausal women could shed light on fundamental mechanisms underlying the neurological and psychiatric comorbidities present during this important transitional phase in women's lives.
迄今为止，与更年期相关的记忆和认知缺陷的潜在机制尚未阐明。因此，我们在一个具有转化效度的更年期小鼠模型——4-乙烯基环己烯二环氧化物诱导的加速卵巢衰竭模型中，研究了脑振荡、它们的相位-振幅耦合、睡眠和警觉状态模式、转轮使用情况以及其他行为指标。加速卵巢衰竭后，雌性小鼠的脑节律出现显著改变，包括θ（5-12赫兹）和γ（30-120赫兹）振荡频率的变化、相位-振幅耦合的逆转、海马体尖波涟漪与内侧前额叶皮质睡眠纺锤波耦合的改变，以及在非快速眼动睡眠期间两个区域之间δ振荡（0.5-4赫兹）同步性的降低。此外，我们报告了θ和γ振荡频率的显著昼夜变化，以及转轮运行期间大量同步的δ振荡。我们的研究结果揭示了加速卵巢衰竭更年期小鼠模型中新颖且特定的网络改变以及脑连接性降低的可行迹象。综上所述，我们的研究结果可能已经确定了一些可能导致该模型中先前描述的某些记忆和认知缺陷的变化。未来针对绝经后女性的相应研究可能会揭示女性生命中这一重要过渡阶段所存在的神经和精神共病的潜在基本机制。
