title: The role of glucocorticoid receptors in dexamethasone-induced apoptosis of neuroprogenitor cells in the hippocampus of rat pups.
abstract: 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.
  
  
  CONCLUSIONS
  Early administration of Dex results in apoptosis of neural progenitor cells in the hippocampus and this is mediated through GCRs.
authors: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Chun-I
authors: CI
authors: Sze
authors: Yung-Chieh
authors: YC
authors: Lin
authors: Yuh-Jyh
authors: YJ
authors: Lin
authors: Ting-Hui
authors: TH
authors: Hsieh
authors: Yu Min
authors: YM
authors: Kuo
authors: Chyi-Her
authors: CH
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015735:Mifepristone / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone
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