Department of Psychology and Neuroscience Program, University of Guelph, Guelph, ON, Canada.
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
Psychoneuroendocrinology. 2021 Jun;128:105232. doi: 10.1016/j.psyneuen.2021.105232. Epub 2021 Apr 15.
Estrogens rapidly facilitate learning and memory, including social recognition - the ability of an animal to recognize another. In ovariectomized female mice, systemic or dorsal hippocampal administration of 17β-estradiol (E2) facilitates short-term social recognition memory within 40 min. Within the same timeframe, E2 increases dendritic spine density in CA1 dorsal hippocampal neurons of behavioural task-naïve mice and in hippocampal sections. Mechanisms underlying these effects remain unclear. Estrogens rapidly modulate actin cytoskeletal dynamics through actin polymerization and the translation of key synaptic proteins. We first determined doses of actin polymerization inhibitor latrunculin A (LAT) and protein synthesis inhibitor anisomycin (ANI) that would block short-term social recognition memory when infused into the dorsal hippocampus of ovariectomized female mice 15 min prior to testing. The highest doses that did not block social recognition prevented the facilitating effects of E2, whereas DNA transcription inhibitor, actinomycin D, could not block social recognition. As task performance may interfere with E2-facilitated increases in dendritic spine density, dendritic spine density and length were examined in task-performing and task-naïve mice. E2 increased dendritic spine density 15 but not 40 min following treatment, regardless of whether the animal had performed the social recognition task. This effect was blocked by LAT, but not ANI. Thus, both actin polymerization and protein synthesis are necessary for E2 to rapidly facilitate social recognition, whereas actin polymerization, but not protein synthesis, is required for the rapid increase in dendritic spine density brought on by E2.
雌激素能迅速促进学习和记忆，包括社交识别——动物识别另一个动物的能力。在去卵巢雌性小鼠中，全身或海马背侧给予 17β-雌二醇（E2）可在 40 分钟内促进短期社交识别记忆。在相同的时间内，E2 增加了行为任务新手小鼠和海马切片中海马 CA1 背侧神经元的树突棘密度。这些作用的机制尚不清楚。雌激素通过肌动蛋白聚合和关键突触蛋白的翻译迅速调节肌动蛋白细胞骨架动力学。我们首先确定了肌动蛋白聚合抑制剂 latrunculin A（LAT）和蛋白合成抑制剂 anisomycin（ANI）的剂量，这些剂量在测试前 15 分钟注入去卵巢雌性小鼠的海马背侧时会阻断短期社交识别记忆。不会阻断社交识别的最高剂量可防止 E2 的促进作用，而 DNA 转录抑制剂放线菌素 D 不能阻断社交识别。由于任务表现可能会干扰 E2 促进的树突棘密度增加，因此在执行任务和未执行任务的小鼠中检查了树突棘密度和长度。E2 增加了树突棘密度，在治疗后 15 分钟而不是 40 分钟，无论动物是否执行了社交识别任务。该作用被 LAT 阻断，但不能被 ANI 阻断。因此，肌动蛋白聚合和蛋白质合成对于 E2 迅速促进社交识别都是必需的，而对于 E2 迅速增加树突棘密度，肌动蛋白聚合而非蛋白质合成是必需的。
