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

A Single Postnatal Dose of Dexamethasone Enhances Memory of Rat Pups Later in Life

“…We previously demonstrated that administering a single dose of Dex to P1 rat pups increased apoptosis in the dentate gyrus at P2 [12]. However in the current study, performance of behavioral tasks and morphology of granular cells at P56 were not impaired (Figs 1 and 3).…”

“…Dex administration reduces cerebral gray matter volume, indicating that it may potentially affect certain types of neuronal cells [8–10]. The affinity of Dex for the glucocorticoid receptors (GRs) is higher than mineralocorticoid receptors (MRs) [11,12]. In addition, the effects of glucocorticoids on learning and memory may be mediated through GRs [13].…”

“…We reported that a single dose of Dex administered in P1 rat pups increases apoptosis in the dentate gyrus [12]. In contrast, this phenomenon is not prominent in P7 pups that received the same treatment.…”

Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study

“…Similarly, the use of DEX has been associated with decreased apoptosis but with deleterious effects including a reduction in insulin-secreting cells [49], a decrease of neural progenitor cells in the hippocampus [50] and diminishing oligodendrocyte progenitor cells resulting in hypomyelination. More recently, a study showed that DEX increases apoptosis in osteoblast and osteocytes, leading to bone loss [51].…”

Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis

“…42 Methotrexate is associated with white matter changes in the brain, 43 acute seizures and paralysis, 44,45 and neurocognitive changes. 46 Corticosteroids can result in behavior changes 47 and decreased hippocampal functioning. 48 Vincristine can cause peripheral neuropathy.…”