糖皮质激素受体在地塞米松诱导的幼鼠海马神经祖细胞凋亡中的作用。

The role of glucocorticoid receptors in dexamethasone-induced apoptosis of neuroprogenitor cells in the hippocampus of rat pups.

机构信息

Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Mediators Inflamm. 2013;2013:628094. doi: 10.1155/2013/628094. Epub 2013 Jan 14.

BACKGROUND

Dexamethasone (Dex) has been used to reduce inflammation in preterm infants with assistive ventilation and to prevent chronic lung diseases. However, Dex treatment results in adverse effects on the brain. Since the hippocampus contains a high density of glucocorticoid receptors (GCRs), we hypothesized that Dex affects neurogenesis in the hippocampus through inflammatory mediators.

METHODS

Albino Wistar rat pups first received a single dose of Dex (0.5 mg/kg) on postnatal day 1 (P1) and were sacrificed on P2, P3, P5, and P7. One group of Dex-treated pups (Dex-treated D1D2) was given mifepristone (RU486, a GCR antagonist) on P1 and sacrificed on P2. Hippocampi were isolated for western blot analysis, TUNEL, cleaved-caspase 3 staining for cell counts, and morphological assessment. Control pups received normal saline (NS).

RESULTS

Dex reduced the developmental gain in body weight, but had no effect on brain weight. In the Dex-treated D1D2 group, apoptotic cells increased in number based on TUNEL and cleaved-caspase 3 staining. Most of the apoptotic cells expressed the neural progenitor cell marker nestin. Dex-induced apoptosis in P1 pups was markedly reduced (60%) by pretreatment with RU486, indicating the involvement of GCRs.

CONCLUSION

Early administration of Dex results in apoptosis of neural progenitor cells in the hippocampus and this is mediated through GCRs.

背景

地塞米松（Dex）已被用于减轻辅助通气的早产儿的炎症，并预防慢性肺部疾病。然而，Dex 治疗会对大脑产生不良反应。由于海马体含有高密度的糖皮质激素受体（GCRs），我们假设 Dex 通过炎症介质影响海马体中的神经发生。

方法

白化 Wistar 幼鼠首先在出生后第 1 天（P1）接受单次 Dex（0.5mg/kg）剂量，然后在 P2、P3、P5 和 P7 处死。一组 Dex 处理的幼鼠（Dex 处理的 D1D2）在 P1 给予米非司酮（RU486，GCR 拮抗剂），并在 P2 处死。分离海马体进行 Western blot 分析、TUNEL、cleaved-caspase 3 染色以进行细胞计数和形态评估。对照幼鼠接受生理盐水（NS）。

结果

Dex 减少了体重的发育性增加，但对脑重没有影响。在 Dex 处理的 D1D2 组中，TUNEL 和 cleaved-caspase 3 染色显示凋亡细胞数量增加。大多数凋亡细胞表达神经祖细胞标志物巢蛋白。RU486 预处理明显减少了 P1 幼鼠中 Dex 诱导的凋亡（60%），表明 GCRs 的参与。