Premium
Low‐Dose Dexamethasone Treatment Promotes the Pro‐Survival Signalling Pathway in the Adult Rat Prefrontal Cortex
Author(s) -
Drakulić D.,
Veličković N.,
Stanojlović M.,
Grković I.,
Mitrović N.,
Lavrnja I.,
Horvat A.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12037
Subject(s) - dexamethasone , endocrinology , medicine , poly adp ribose polymerase , apoptosis , prefrontal cortex , corticosterone , glucocorticoid , protein kinase b , dna fragmentation , glucocorticoid receptor , receptor , biology , programmed cell death , polymerase , hormone , biochemistry , enzyme , cognition , neuroscience
Synthetic glucocorticoid dexamethasone ( DEX ), a highly potent anti‐inflammatory and immunosuppressive agent, is widely used in the treatment of brain cancer, as well as for inflammatory and autoimmune diseases. The present study aimed to determine whether low‐dose subchronic DEX treatment (100 μg/kg for eight 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, B ax] and cell‐survival molecules ( AKT , B cl‐2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1 day after the last DEX injection. In the PFC , DEX caused activation of AKT , augmentation of pro‐survival B cl‐2 protein and an enhanced B cl‐2/ B ax protein ratio, as well B cl‐2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP , procaspase 3 and B ax was detected, whereas p53 protein was decreased. Reverse transcriptase ‐ polymerase chain reaction analysis showed a decrease of p53 m RNA levels and no significant difference in B cl‐2 and B ax m RNA expression in DEX ‐treated rats. Finally, a DNA fragmentation assay and Fluoro‐Jade staining demonstrated no considerable changes in apoptosis in the rat PFC . Our findings support the concept that low‐dose DEX creates a hypocorticoid state in the brain and also indicate that subchronic DEX treatment activates the pro‐survival signalling pathway but does not change apoptotic markers in the rat PFC . This mechanism might be relevant for the DEX ‐induced apoptosis resistance observed during and after chemotherapy of patients with brain tumours.