Bayer Janine, Rune Gabriele, Schultz Heidrun, Tobia Michael J, Mebes Imke, Katzler Olaf, Sommer Tobias
Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Psychoneuroendocrinology. 2015 Jun;56:213-25. doi: 10.1016/j.psyneuen.2015.03.011. Epub 2015 Mar 21.
17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease.
17-β-雌二醇（E2）可促进长期增强效应（LTP），并增加去卵巢啮齿动物海马神经元中的棘突突触密度。与这些在细胞水平上的有益作用一致，E2可改善依赖海马体的记忆。研究E2在啮齿动物中作用的一种主要方法是通过来曲唑抑制其合成，这会降低LTP和棘突突触密度。在当前的纵向功能磁共振成像（fMRI）研究中，我们将这种方法应用于人类，并比较了E2合成抑制对服用来曲唑的绝经后女性（n = 21）与对照组（n = 24）的记忆表现和海马体活动的影响。具体而言，我们采用了各种行为记忆范式，以区分依赖海马体和不依赖海马体的记忆。与关于啮齿动物的文献一致，E2合成抑制特异性地损害了依赖海马体的记忆，然而，并非所有采用的范式都受到同等程度的影响。在神经元水平上，E2耗竭倾向于在编码过程中降低海马体活动，而在扣带回前部和背外侧前额叶皮质中增加活动。因此，我们推断E2合成抑制特异性地损害了人类的海马体功能，而前额叶活动增加可能反映了一种补偿机制，这在认知衰老和阿尔茨海默病研究中已经为人所知。
