Low-Dose Dexamethasone Treatment Promotes Pro-Survival Signalling Pathway In Adult Rat Prefrontal Cortex.
Synthetic glucocorticoid dexamethasone (DEX), a highly potent anti-inflammatory and immunosuppressive agent, is widely used in treatments of brain cancer, inflammatory and autoimmune diseases. The objective of the current study was to determine whether a low-dose subchronic DEX treatment (100 μg/kg for 8 consecutive days) exerts long-term effects on apoptosis in the adult rat prefrontal cortex (PFC) by examining the expression of cell death-promoting molecules (poly (ADP-ribose) polymerase (PARP), p53, procaspase 3, cleaved caspase 3, Bax) and cell-survival molecules (AKT, Bcl-2). Our results revealed that body, thymus and adrenal weight as well corticosterone level in the serum and PFC were reduced a day following last DEX injection. In PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to mitochondria. The unaltered profile in the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, while the p53 protein was decreased. Results of RT-PCR analysis showed decrease of p53 mRNA level and no significant difference in Bcl-2 and Bax mRNA expressions in DEX-treated rats. Finally, the DNA fragmentation assay and Fluoro-Jade staining demonstrated no considerable changes in the apoptosis in rat PFC. Our findings support the concept that a low-dose DEX creates the hypocorticoid state in the brain and indicate that subchronic DEX treatment activates pro-survival signalling pathway but does not change apoptotic markers in rat PFC. This mechanism might be relevant for DEX-induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours. © 2013 British Society for Neuroendocrinology.
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T30 T31 T32
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y
DEX DEX DEX DEX dexamethasone DEX DEX poly (ADP-ribose) corticosterone DEX DEX Dexamethasone Bax p53 p53 Bcl-2 Bax poly (ADP-ribose) polymerase PARP p53 procaspase 3 caspase 3 Bax AKT Bcl-2 AKT Bcl-2 Bcl-2 Bax Bcl-2 PARP procaspase 3