实用医学杂志 ›› 2022, Vol. 38 ›› Issue (12): 1480-1485.doi: 10.3969/j.issn.1006⁃5725.2022.12.008

• 基础研究 • 上一篇    下一篇

胎盘糖皮质激素受体低表达对孕期抑郁模型雌性子代的影响

潘淑敏1 曹雄2 王志坚1   

  1. 1 南方医科大学南方医院妇产科(广州510445);2 教育部精神健康研究重点实验室,粤港澳大湾区脑科学 与类脑研究中心,广东省重大精神疾病研究重点实验室,南方医科大学基础医学神经生物教研室(广州 510515)

  • 出版日期:2022-06-25 发布日期:2022-06-25
  • 通讯作者: 王志坚 E⁃mail:wzjnfyy @163.com
  • 基金资助:
    广东省自然科学基金(编号:201904020039)

Knockdown of NR3C1 in perinatal depressed mice produced depressive⁃like behaviors in female offspring

PAN Shumin*,CAO Xiong,WANG Zhijian.   

  1. Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510445,China 

  • Online:2022-06-25 Published:2022-06-25
  • Contact: WANG Zhijian E⁃mail:wzjnfyy @163.com

摘要:

目的 探索糖皮质激素受体(GR)对孕期抑郁小鼠子代抑郁倾向的影响。方法 利用普通 小鼠进行孕期抑郁(PND)造模,并用 Western blot 检测不同性别胎盘绒毛中 GR 表达情况;利用转基因工具 鼠获得胎盘 GR 敲低小鼠,共 20 只。Western blot 检测胎盘 GR 敲低效果并分析胎盘组织学改变;对胎盘 GR 敲低小鼠进行孕期抑郁造模,比较 GR 敲低组抑郁孕鼠的仔鼠(KD)与 GR 非敲低组仔鼠(N⁃KD)生长发 育情况;动物行为实验检测仔鼠运动能力和抑郁倾向。结果 PND小鼠雌性仔鼠胎盘绒毛GR表达显著升 高(P < 0.05);胎盘GR敲低小鼠的胎盘GR表达显著降低(P < 0.05);KD组仔鼠胎盘形态未见异常(P > 0.05); KD 组仔鼠生长发育未见异常(P > 0.05);KD 组仔鼠成年后运动能力未见异常(P > 0.05);KD 组雌性仔鼠 在成年后更有抑郁倾向(P < 0.05)。结论 敲低胎盘GR 可能增加孕期抑郁小鼠雌性子代抑郁倾向。

关键词:

糖皮质激素受体, 孕期抑郁, 条件性敲低, 转基因小鼠

Abstract:

Objective To explore the role of glucocorticoid receptors(GRs)in the depressive⁃like behaviors of offspring of perinatally depressed mice(PND). Methods Western blot was applied to detect the expression of GRs in PND mice generated with wild⁃type mice. Twenty mice with the placenta GR knocked down were generated using transgenic mice. Then western blot was used to verify the knockdown of the GRs in the mice,and the mor⁃ phology of the mice was analyzed. Pregnant GRs knocked down mice were stimulated continuously to be used to compare the growth and development of offspring of the GRs knockdown group(KD)and the GRs non⁃knockdown group(N⁃KD);The locomotion behaviors and depressive⁃like behaviors of each group′s offspring were detected by open field test(OFT)and the forced swimming test(FST). Results Compared with the control group,the level of GRs was increased in the placenta of female offspring of PND mice(P < 0.05);The expression of GRs in placenta of KD decreased significantly(P < 0.05);We observed no significant differences between the KD and N⁃KD in placental morphology(P > 0.05);The growth and development and the exercise capacity of the KD and N⁃KD showed no significant differences(P > 0.05);However,the female offspring of KD had more depressive tendencies than the male offspring(P < 0.05). Conclusion A decrease in placental GRs augments the tendency of female offspring of PND mice to depression.

Key words:

GR, perinatal depression, conditional gene knockdown, transgenic mice