Estrogen and the Aging Primate Brain

这项跨机构合作的活动扩展了我们对雌激素对恒河猴神经元老化标记物与认知结果的影响的调查。在最近发表的一项此类研究中，Crimins et al.（2019）使用了加州大学戴维斯分校莫里森小组开创的连续切片电子显微镜方法，在年轻和老年猴子的绝经和雌激素替代的卵巢切除模型中，量化了背外侧前额叶皮层第三层中磷酸化tau（丝氨酸214; pS214-tau）的突触室表现。免疫金pS214-tau标记的水平下降，随着年龄的增长，在所有的突触隔室检查。然而，这些影响与认知和雌激素状态无关。尽管磷酸化tau蛋白通常在与年龄相关的神经病理学背景下受到关注，但我们在猴子中的发现共同指出了pS214-tau在支持突触健康方面的潜在生理作用。这类研究填补了理解突触脆弱性基础的关键空白，突触脆弱性越来越被认为是神经退行性疾病的关键种子事件。

Activity on this trans-institutional collaborative has extended our survey of estrogenic effects on markers of neuronal aging in relation to cognitive outcomes in rhesus monkeys. In a recently published study of this sort, Crimins et al. (2019) used serial section electron microscopy methods pioneered by the Morrison group at UC Davis to quantify the synaptic compartmental representation of phosphorylated tau (at serine 214; pS214-tau) in layer III of the dorsolateral prefrontal cortex in an ovariectomized model of menopause and estrogen replacement in young and aged monkeys. Levels of immunogold pS214-tau labeling were decreased with aging in all synaptic compartments examined. These effects, however, were independent of cognitive and estrogen status. Although phosphorylated tau has typically been of interest in the context of age-related neuropathology, taken together our findings in monkeys point a potential physiological role for pS214-tau in supporting synaptic health. Studies of this sort fill a critical gap in understanding the basis of synaptic vulnerabilities that are increasingly recognized as a key seed event in neurodegenerative disease.