Alia-Klein Nelly, Preston-Campbell Rebecca N, Kim Sung Won, Pareto Deborah, Logan Jean, Wang Gene-Jack, Moeller Scott J, Fowler Joanna S, Biegon Anat
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Missouri Institute of Mental Health, St. Louis, MO, United States.
Front Neurosci. 2020 Oct 19;14:565668. doi: 10.3389/fnins.2020.565668. eCollection 2020.
The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cognitive performance in relation to brain aromatase availability in healthy men and women. Twenty-seven healthy participants were administered tests of verbal learning and memory and perceptual/abstract reasoning. images of brain aromatase availability were acquired in this sample using positron emission tomography (PET) with the validated aromatase radiotracer [C]vorozole. Regions of interest were placed bilaterally on the amygdala and thalamus where aromatase availability is highest in the human brain. Though cognitive performance and aromatase availability did not differ as a function of sex, higher availability of aromatase in the amygdala was associated with lower cognitive performance in men. No such relationship was found in women; and the corresponding regression slopes were significantly different between the sexes. Thalamic aromatase availability was not significantly correlated with cognitive performance in either sex. These findings suggest that the effects of brain aromatase on cognitive performance are both region- and sex-specific and may explain some of the normal variance seen in verbal and nonverbal cognitive abilities in men and women as well as sex differences in the trajectory of cognitive decline associated with Alzheimer's disease.
芳香化酶催化雌激素生物合成的最后一步，将睾酮转化为雌二醇，并且在所有哺乳动物的大脑中均有表达。雌激素被认为对维持女性的认知功能很重要，而睾酮被认为可调节男性的认知能力。在此，我们比较了健康男性和女性在认知表现方面与大脑芳香化酶可用性相关的差异。对27名健康参与者进行了语言学习与记忆以及感知/抽象推理测试。使用经过验证的芳香化酶放射性示踪剂[C]伏罗唑，通过正电子发射断层扫描（PET）在此样本中获取大脑芳香化酶可用性的图像。在杏仁核和丘脑双侧放置感兴趣区域，这两个区域在人类大脑中芳香化酶可用性最高。尽管认知表现和芳香化酶可用性并未因性别而有所不同，但杏仁核中较高的芳香化酶可用性与男性较低的认知表现相关。在女性中未发现这种关系；并且两性之间相应的回归斜率存在显著差异。丘脑芳香化酶可用性与两性的认知表现均无显著相关性。这些发现表明，大脑芳香化酶对认知表现的影响具有区域和性别特异性，并且可能解释了男性和女性在语言和非语言认知能力方面所见的一些正常差异，以及与阿尔茨海默病相关的认知衰退轨迹中的性别差异。
