Sex and region-specific effects of variable stress on microglia morphology.
Sex and region-specific effects of variable stress on microglia morphology.
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DOI：
10.1016/j.bbih.2021.100378
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Hodes GE
中科院分区：
文献类型：
--
作者：
Tsyglakova M;Huskey AM;Hurst EH;Telep NM;Wilding MC;Babington ME;Rainville JR;Hodes GE
重度抑郁症 (MDD) 是一种常见且令人衰弱的情绪障碍，女性比男性更常见。在人类中，小胶质细胞激活的 PET 成像目前正在探索作为 MDD 和自杀意念的潜在生物标志物。压力是许多情绪障碍的诱因，包括抑郁症。据报道，不同大脑区域的小胶质细胞因应激而发生形态和激活状态的变化，但大多数研究仅检查男性受试者。在这里，我们报告了雄性和雌性小鼠在持续 6 或 28 天的可变应激后伏隔核 (NAc) 和海马亚区 (HPC) 的小胶质细胞形态的变化。我们的数据表明，经过 6 天的应激后，女性 NAc 和齿状回中的小胶质细胞的稳态相关形态减少，而启动的小胶质细胞增加。 28 天后，一些性别特异性应激效应仍然存在于 NAc 内的小胶质细胞中，但不存在于齿状回中。 CA1 中任一时间点的任一性别均未受到压力的影响。在雌性小鼠中，使用罗格列酮抗炎激活小胶质细胞，在 6 天的压力后促进了社交行为。此外，药物和应激都会影响 NAc 中小胶质细胞的形态和激活状态。这些数据表明，小胶质细胞的形态和激活状态会因区域特异性的方式而受到 6 天的可变应激的改变，并且可能有助于或可能补偿应激敏感性的发生，而不是影响长期暴露于应激。压力对小胶质细胞有区域和性别特异性影响。雌性小胶质细胞对较短时间的压力反应更强烈。罗格列酮可增加应激雌性小鼠的社交互动。罗格列酮不会阻止女性应激诱导的小胶质细胞激活。
Major Depressive Disorder (MDD) is a common and debilitating mood disorder that is more prevalent in women than men. In humans, PET imaging of microglia activation is currently being explored as a potential biomarker of MDD and suicidal ideation. Stress is a trigger for many mood disorders, including MDD. Microglial changes in morphology and activation state in response to stress has been reported in various brain regions, but most studies only examined male subjects. Here we report changes in microglia morphology in the nucleus accumbens (NAc) and subregions of the hippocampus (HPC) in both male and female mice following variable stress of 6 or 28 days in duration. Our data demonstrate that after 6 days of stress, microglia in the female NAc and dentate gyrus have a reduction in homeostatic associated morphology and an increase in primed microglia. After 28 days some of these sex specific stress effects were still present in microglia within the NAc but not the dentate gyrus. There were no effects of stress in either sex at either timepoint in CA1. In female mice, anti-inflammatory activation of microglia using rosiglitazone promoted sociability behavior after 6 days of stress. Furthermore, both drug and stress have impact on microglia morphology and activation state in the NAc. These data suggest that microglia morphology and activation state are altered by 6 days of variable stress in a region-specific manner and may contribute to, or potentially compensate for, the onset of stress susceptibility rather than impacting long term exposure to stress. There are region and sex specific effects of stress on microglia. Female microglia respond more strongly to shorter periods of stress. Rosiglitazone increases social interaction in stressed female mice. Rosiglitazone does not block stress induced microglia activation in females.
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影响因子：
3.3
作者：
Brancato A;Bregman D;Ahn HF;Pfau ML;Menard C;Cannizzaro C;Russo SJ;Hodes GE
通讯作者：
Hodes GE
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
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影响因子：
7.8
作者：
Ji J;Xue TF;Guo XD;Yang J;Guo RB;Wang J;Huang JY;Zhao XJ;Sun XL
通讯作者：
Sun XL
影响因子：
8.8
作者：
Guneykaya, Dilansu;Ivanov, Andranik;Wolf, Susanne A.
通讯作者：
Wolf, Susanne A.
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.