丰富环境通过上调海马 LASP1 改善父系应激致 子代小鼠焦虑抑郁样行为.

Objective To explore the role of environmental enrichment (EE) in paternal stress-induced anxiety and depression-like behaviors in offspring and its potential mechanisms. Methods Male C57BL/6 mice (FO) were treated with unpredictable chronic mild stress (UCMS) and subsequently mated with normal females to obtain F1 offspring mice. The standard environment (SE) and enriched environment (EE) were administered to F1-UCMS offspring mice during their early life (3-5 weeks of age). Anxiety-like behaviors were detected by open field test (OFT) and elevated plus-maze test (EPM); depression-like behaviors were detected via forced swimming test (FST) and sucrose preference test (SPT) at the age of 8 weeks. The expressions of LIM and SH3 domain protein 1 (LASP1) in the hippocampus of adult F1 offspring mice were detected by Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Results Compared to F1 offspring of normal paternal (F1-Nor), F1 offspring mice of the stressed paternal (F1-UCMS) showed significantly anxiety-like behavior with reduced percentage of time spent in the central region of OFT and in the open arm of EPM (P<0.05); mice from the F1-UCMS group showed a significantly increased percentage of immobility in FST and a reduced percentage of sugar consumption in SPT (P<0.01), which demonstrated significant depression-like behaviors. Compared to the SE group, mice in the EE group had an increased percentage of time spent in the central region of the OFT [males: (7.44±0.75)% vs. (14.93±1.74) %, P<0.01; females: (8.89±1.06) % vs. (15.10±1.82) %, P<0.05] and an increased percentage of time in the open arm of EPM [males: (8.09±1.05) % vs. (14.15±1.88)%, P<0.05; females: (9.13±1.14)% vs. (14.04±1.37) %, P<0.05]. This indicated that EE ameliorated anxiety-like behavior in F1-UCMS mice with paternal stress. Compared to the SE group, mice in the EE group had an decreased percentage of immobility in FST [males: (58.63±4.51)% vs. (42.15±3.81)%, P<0.05; females: (57.96±4.19)% vs. (43.254.22)%, P<0.05] and an increased percentage of sugar consumption in SPT [males: (50.38±3.47)% vs. (70.393.12) %, P<0.01; females: (52.42±2.84) % vs. (69.99 ±3.55)%, P<0.01]. This indicated that EE ameliorated depression-like behavior in F1-UCMS mice with paternal stress. Hippocampal LASP1 expression was reduced in SE group compared to F1-Nor group (males: P<0.01; females: P<0.05), while LASP1 was increased in EE group compared to SE group (P<0.05) detected by RT-qPCR and Western blotting. Conclusion EE ameliorates paternal stress-induced anxiety and depression-like behaviors in F1-UCMS mice, and the mechanism may be associated with increased hippocampal LASP1 expression in F1-UCMS mice. [ABSTRACT FROM AUTHOR]

目的 探索丰富环境 (environmental enrichment, EE) 在父系应激致子代焦虑、抑郁样行为中的作用及其可能机 制。方法 给予雄性 C57BL/6小鼠 (F0) 慢性温和不可预知应激 (unpredictable chronic mild stress, UCMS), 随后与 正常雌鼠交配获得 F1 子代 (F1-UCMS) 小鼠。在 F1-UCMS子代小鼠幼年期 (3~5 周龄) 分别给予标准环境 (standard environment, SE) 和丰富环境 (EE) 干预, 成年后 (8周龄) 采用旷场实验 (open field test, OFT) 、高架十字迷宫实验 (elevated plus-maze test, EPM) 检测小鼠焦虑样行为, 采用强迫游泳实验 (forced swimming test, FST) 、糖水偏好实 验 (sucrose preference test, SPT) 检测小鼠抑郁样行为。通过实时荧光定量 PCR (Real-time fluorescence quantitative PCR, RT-qPCR) 和蛋白免疫印迹 (Western blotting) 检测成年 F1-UCMS 小鼠海马 LIM 和 SH3 结构域蛋白1 (LIM and SH3 domain protein 1, LASP1) 的 表 达。结 果 与 正 常 父 系 的 F1 子 代 (F1-Nor) 相 比, 应 激 父 系 的 F1 子 代 F1-UCMS 小鼠在 OFT 的中央区域停留时间百分比减少、EPM 的开放臂停留时间百分比减少 (P 均<0.05), 表现出 明显焦虑样行为; F1-UCMS 组小鼠在 FST 的不动时间百分比增加、SPT 的糖水消耗百分比减少 (P 均<0.01), 表现 出明显抑郁样行为。与SE组相比, EE 组小鼠在 OFT 的中央区域停留时间百分比增加[雄性: (7.44±0.75)% vs. (14.93±1.74)%, P<0.01; 雌性: (8.89±1.06) %vs. (15.10±1.82)%, P<0.05]、EPM 的开放臂停留时间百分比增 加[雄性: (8.09±1.05)%vs. (14.15±1.88) %, P<0.05; 雌性: (9.13±1.14) % vs. (14.04±1.37)%, P<0.05], 表明 EE改善父系应激导致的 F1-UCMS小 鼠 焦 虑 样 行 为; EE 组 小 鼠 在 FST 的 不 动 时 间 百 分 比 减 少[雄 性: (58.63± 4.51) %vs. (42.15±3.81)%, P<0.05; 雌性: (57.96±4.19)% vs. (43.25±4.22)%, P<0.05]、SPT 的糖水消耗百分 比增加[雄性: (50.38±3.47) %vs. (70.39±3.12)%, P<0.01; 雌性: (52.42±2.84)%vs. (69.99±3.55)%, P<0.01], 表 明 EE 改善父系应激导致的 F1-UCMS小鼠抑郁样行为。RT-qPCR 及 Western blotting 检测结果显示, 与 F1-Nor组 相比, SE 组子代小鼠海马 LASP1 表达减少 (雄性P<0.01, 雌性 P<0.05); 与 SE组相比, EE组小鼠海马 LASP1表 达增加 (P 均<0.05) 。结论 EE 可改善父系应激导致的 F1-UCMS 小鼠焦虑、抑郁样行为, 其机制可能与 F1-UCMS 小鼠海马 LASP1表达增加相关。 [ABSTRACT FROM AUTHOR]