The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups
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), w...
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/628094 |
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| author | Chun-I Sze Yung-Chieh Lin Yuh-Jyh Lin Ting-Hui Hsieh Yu Min Kuo Chyi-Her Lin |
| author_facet | Chun-I Sze Yung-Chieh Lin Yuh-Jyh Lin Ting-Hui Hsieh Yu Min Kuo Chyi-Her Lin |
| author_sort | Chun-I Sze |
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| description | 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. |
| format | Article |
| id | doaj-art-b805e2abd4ed4afebb91a5ffb2ba48f0 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b805e2abd4ed4afebb91a5ffb2ba48f02025-02-03T01:22:34ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/628094628094The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat PupsChun-I Sze0Yung-Chieh Lin1Yuh-Jyh Lin2Ting-Hui Hsieh3Yu Min Kuo4Chyi-Her Lin5Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, TaiwanBackground. 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.http://dx.doi.org/10.1155/2013/628094 |
| spellingShingle | Chun-I Sze Yung-Chieh Lin Yuh-Jyh Lin Ting-Hui Hsieh Yu Min Kuo Chyi-Her Lin The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups Mediators of Inflammation |
| title | The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups |
| title_full | The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups |
| title_fullStr | The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups |
| title_full_unstemmed | The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups |
| title_short | The Role of Glucocorticoid Receptors in Dexamethasone-Induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups |
| title_sort | role of glucocorticoid receptors in dexamethasone induced apoptosis of neuroprogenitor cells in the hippocampus of rat pups |
| url | http://dx.doi.org/10.1155/2013/628094 |
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