Department of Anatomy and Neuroscience, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Neurosci. 2022 Oct;56(8):5137-5153. doi: 10.1111/ejn.15812. Epub 2022 Sep 3.
Recent studies have indicated that some individuals are less affected by stress, and such individuals are called resilient. This study aimed to determine whether the specific phenotype of microglia might be involved in resilience using the social defeat stress paradigm. Male C57BL/6J (B6) mice were attacked by aggressive male ICR mice for five consecutive days. After stress exposure, the social behaviour was reduced in about half of the B6 mice (vulnerable), whereas no such change was observed in the remaining half of the B6 mice (resilient). Anxiety-like behaviour was increased in vulnerable mice compared with resilient mice and non-stressed controls. However, depression-related behaviour was comparable between the three groups. The morphological characteristics of microglia in the CA1 region of the dorsal hippocampus in non-stressed controls and resilient mice differed from those in vulnerable mice. Interestingly, the voxel densities of GABAergic and glutamatergic synaptic puncta colocalized with microglia were higher in resilient mice than in non-stressed controls and vulnerable mice. Microglia were then objectively classified into three morphological types by hierarchical cluster analysis. The appearance of type I microglia resembled the so-called resting ramified microglia and represented the major population of microglia in non-stressed controls. Type II microglia exhibited a de-ramified morphology and accounted for 60% of the microglia in vulnerable mice. Type III microglia showed a hyper-ramified morphology and represented more than half of the microglia in resilient mice. These results suggest that hyper-ramified microglia in the hippocampus may be associated with stress resilience via the modulation of synaptic transmission.
最近的研究表明，有些人受压力的影响较小，这些人被称为有弹性的。本研究旨在使用社交挫败应激模型，确定小胶质细胞的特定表型是否与弹性有关。雄性 C57BL/6J (B6) 小鼠连续 5 天受到攻击性 ICR 雄性小鼠的攻击。应激暴露后，约一半的 B6 小鼠（脆弱）的社交行为减少，而另一半 B6 小鼠（弹性）则没有观察到这种变化。与弹性小鼠和非应激对照组相比，脆弱小鼠的焦虑样行为增加。然而，三组之间的抑郁相关行为相当。非应激对照组和弹性小鼠海马背侧 CA1 区小胶质细胞的形态特征与脆弱小鼠不同。有趣的是，与非应激对照组和脆弱小鼠相比，弹性小鼠中 GABA 能和谷氨酸能突触 puncta 与小胶质细胞共定位的体素密度更高。通过层次聚类分析，小胶质细胞随后被客观地分为三种形态类型。I 型小胶质细胞的外观类似于所谓的静止分支状小胶质细胞，代表非应激对照组中小胶质细胞的主要群体。II 型小胶质细胞表现出去分支形态，占脆弱小鼠中小胶质细胞的 60%。III 型小胶质细胞表现出超分支形态，代表弹性小鼠中小胶质细胞的一半以上。这些结果表明，海马体中的超分支小胶质细胞可能通过调节突触传递与应激弹性有关。
