The Role of Glucocorticoid Receptors in Dexamethasone-induced Apoptosis of Neuroprogenitor Cells in the Hippocampus of Rat Pups

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2013 Feb 13

PMID 23401645

Citations 18

Authors

Chun-I Sze

Yung-Chieh Lin

Yuh-Jyh Lin

Ting-Hui Hsieh

Yu Min Kuo

Chyi-Her Lin

Affiliations

Soon will be listed here.

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.

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

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