Background Neuromorphological changes are consistently reported in the prefrontal cortex of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and the potential link to behavioral deficits are relatively unknown. Methods To answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21, or 35 days of chronic restraint stress (CRS). CRS-induced behavioral effects on anhedonia- and anxiety-like behaviors were measured using the sucrose intake and the PhenoTyper tests, respectively. Prefrontal cortex GFP+ or GFAP+ cell morphology was assessed using Sholl analysis, and associations with behavior were determined using correlation analysis. Results CRS-exposed male and female mice displayed anxiety-like behavior at 7, 21, and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells accompanied by increased proximal processes. In males, the number of intersections at the most distal radius step significantly correlated with anhedonia-like behavior (r = 0.622, P < .05) for GFP+ cells and with behavioral emotionality calculated by z-scoring all behavioral measured deficits (r = −0.667, P < .05). Similar but not significant correlations were observed in females. No correlation between GFP+ cell atrophy with anxiety-like behavior was found. Conclusion Chronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic and behavioral changes associated with stress-related disorders.

中文翻译：

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慢性应激改变小鼠前额叶皮层星形胶质细胞形态

背景 在患有压力相关疾病的患者的前额叶皮层和啮齿动物压力模型中一直报告神经形态学变化，但压力对星形胶质细胞形态的影响以及与行为缺陷的潜在联系相对未知。方法为回答这些问题，对在胶质纤维酸蛋白 (GFAP) 启动子下表达绿色荧光蛋白 (GFP) 的转基因小鼠进行 7、21 或 35 天的慢性束缚应激 (CRS)。分别使用蔗糖摄入量和 PhenoTyper 测试测量 CRS 诱导的对快感缺乏和焦虑样行为的行为影响。使用 Sholl 分析评估前额叶皮层 GFP+ 或 GFAP+ 细胞形态，并使用相关分析确定与行为的关联。结果暴露于 CRS 的雄性和雌性小鼠在 7、21 和 35 天时表现出焦虑样行为，在 35 天时表现出快感缺乏样行为。GFAP+ 细胞形态分析显示 CRS 21 天和 35 天后远端突显着萎缩。CRS 诱导 GFP+ 细胞远端半径交叉点的相似减少，同时近端突起增加。在男性中，最远端半径步骤的交叉点数量与 GFP+ 细胞的快感缺乏样行为 (r = 0.622, P < .05) 和通过 z 评分计算的所有行为测量缺陷 (r = -0.667，P < .05)。在女性中观察到类似但不显着的相关性。未发现 GFP+ 细胞萎缩与焦虑样行为之间存在相关性。