Tsai Kuen-Jer, Sze Chun-I, Lin Yung-Chieh, Lin Yuh-Jyh, Hsieh Ting-Hui, Lin Chyi-Her
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
PLoS One. 2016 Oct 31;11(10):e0165752. doi: 10.1371/journal.pone.0165752. eCollection 2016.
Postnatal dexamethasone (Dex) therapy is associated with adverse neurodevelopmental outcomes, which might be related to its timing of administration. We used time-dated pregnant Wistar albino rats, whose litters were divided into experimental (Dex) and control groups intraperitoneally administered one dose of Dex (0.5 mg/kg) or normal saline (NS), respectively, at either day 1 (P1) or 7 (P7). The magnitude of the contextual freezing response and performance on the Morris water maze were significantly higher in the Dex-P7 group than in those of the other groups at P56. Dendritic spine density, membranous expression of the N-methyl-d-aspartate receptor (NMDAR) subunit NR2A/2B, and postsynaptic density-95 (PSD-95) were significantly higher in the Dex-P7 group than in the other groups. Furthermore, cytosolic expression of nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase (PI3K) was significantly higher in the Dex group than in NS group. Moreover, Dex administration at P7 increased cell proliferation, neuronal differentiation, and the survival of newly born neurons in the dentate gyrus. These results suggest Dex at P7 enhances the acquisition of contextual fear and spatial memory later in life due to the modulation of the newly born neurons, increase in dendritic spine number, and NMDAR expression.
产后地塞米松（Dex）治疗与不良神经发育结局相关，这可能与其给药时间有关。我们使用了定时怀孕的Wistar白化大鼠，其幼崽在出生第1天（P1）或第7天（P7）分别分为实验组（Dex）和对照组，腹腔内分别给予一剂Dex（0.5mg/kg）或生理盐水（NS）。在P56时，Dex-P7组的情境性僵住反应程度和在莫里斯水迷宫中的表现显著高于其他组。Dex-P7组的树突棘密度、N-甲基-D-天冬氨酸受体（NMDAR）亚基NR2A/2B的膜表达和突触后致密蛋白95（PSD-95）显著高于其他组。此外，Dex组的核因子κB（NF-κB）和磷脂酰肌醇3激酶（PI3K）的胞质表达显著高于NS组。此外，在P7给予Dex可增加齿状回中的细胞增殖、神经元分化和新生神经元的存活。这些结果表明，P7时给予Dex可通过调节新生神经元、增加树突棘数量和NMDAR表达，增强后期生活中情境性恐惧和空间记忆的获得。
