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

Chun I. Sze, Yung Chieh Lin, Yuh Jyh Lin, Ting Hui Hsieh, Yu Min Kuo, Chyi Her Lin

研究成果: Article同行評審

29 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號628094
期刊Mediators of Inflammation
2013
DOIs
出版狀態Published - 2013

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 細胞生物學

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