Institute of Neuroanatomy, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Institute of Cell Biology and Neurobiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
J Neuroendocrinol. 2023 May;35(5):e13276. doi: 10.1111/jne.13276. Epub 2023 May 11.
Microglia have been shown to sculpt postnatal circuitry from birth up to adulthood due to their role in both synapse formation, synaptic pruning, and the elimination of weak, redundant synapses. Microglia are differentiated in a sex-dependent manner. In this study, we tested whether sexual differentiation of microglia results in sex-dependent postnatal reorganization of CA1 synaptic connectivity in the hippocampus. The stereological counting of synapses in mice using electron microscopy showed a continuous rise in synapse density until the fourth week, followed by a plateau phase and loss of synapses from the eighth week onwards, with no difference between sexes. This course of alteration in synapse numbers did not differ between sexes. However, selectively, on postnatal day (P) 14 the density of synapses was significantly higher in the female than in the male hippocampus. Higher synapse density in females was paralleled by higher activity of microglia, as indicated by morphological changes, CD68 expression, and proximity of microglia to synaptic sites. In Thy1-GFP mice, consistent with increased synapse numbers, bouton density was also clearly increased in females at P14. At this time point, CD47 expression, the "don't eat me" signal of neurons, was similar in males and females. The decrease in bouton density thereafter in conjunction with increased synapse numbers argues for a role of microglia in the formation of multispine boutons (MSB). Our data in females at P14 support the regulatory role of microglia in synapse density. Sexual differentiation of microglia, however, does not substantially affect long-term synaptic reorganization in the hippocampus.
小胶质细胞在突触形成、突触修剪和消除弱的、冗余的突触方面发挥作用，从而塑造出生后至成年期的中枢神经系统回路。小胶质细胞以性别依赖的方式分化。在这项研究中，我们测试了小胶质细胞的性别分化是否导致海马 CA1 突触连接在出生后的性别依赖重组。使用电子显微镜对小鼠突触进行体视学计数显示，突触密度持续增加，直到第四周，然后进入平台期，第八周后开始失去突触，性别之间没有差异。突触数量的这种变化过程在性别之间没有差异。然而，在出生后第 14 天（P14），女性海马体中的突触密度明显高于男性，这种情况具有选择性。女性的突触密度更高，这与小胶质细胞的活性更高有关，表现为形态变化、CD68 表达以及小胶质细胞与突触部位的接近程度。在 Thy1-GFP 小鼠中，与突触数量增加一致，女性在 P14 时的突触及末梢密度也明显增加。在此时点，神经元的“别吃我”信号 CD47 的表达在雄性和雌性之间相似。此后，突触及末梢密度的减少伴随着突触数量的增加，这表明小胶质细胞在多棘突末梢（MSB）的形成中起作用。我们在 P14 时雌性的数据支持小胶质细胞在突触密度调节中的作用。然而，小胶质细胞的性别分化并没有显著影响海马体的长期突触重组。
