TY  - JOUR
AU  - Drakulić, Dunja R
AU  - Veličković, Nataša
AU  - Stanojlović, Milos  R
AU  - Grković, Ivana S
AU  - Mitrović, N
AU  - Lavrnja, Irena
AU  - Horvat, Anica I
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/994
AB  - 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 (100g/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, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1day after the last DEX injection. In the PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA 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.
T2  - Journal of Neuroendocrinology
T1  - Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex
IS  - 7
VL  - 25
SP  - 125
EP  - 616
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_994
ER  - 

@article{
author = "Drakulić, Dunja R and Veličković, Nataša and Stanojlović, Milos  R and Grković, Ivana S and Mitrović, N and Lavrnja, Irena and Horvat, Anica I",
year = "2013",
abstract = "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 (100g/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, Bax] and cell-survival molecules (AKT, Bcl-2). The results obtained revealed that body, thymus and adrenal gland weights, as well corticosterone levels, in the serum and PFC were reduced 1day after the last DEX injection. In the PFC, DEX caused activation of AKT, augmentation of pro-survival Bcl-2 protein and an enhanced Bcl-2/Bax protein ratio, as well Bcl-2 translocation to the mitochondria. An unaltered profile with respect to the protein expression of apoptotic molecules PARP, procaspase 3 and Bax was detected, whereas p53 protein was decreased. Reverse transcriptase -polymerase chain reaction analysis showed a decrease of p53 mRNA levels and no significant difference in Bcl-2 and Bax mRNA 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.",
journal = "Journal of Neuroendocrinology",
title = "Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex",
number = "7",
volume = "25",
pages = "125-616",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_994"
}

Drakulić, D. R., Veličković, N., Stanojlović, Milos  R, Grković, I. S., Mitrović, N., Lavrnja, I.,& Horvat, A. I.. (2013). Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex. in Journal of Neuroendocrinology, 25(7), 125-616.
https://hdl.handle.net/21.15107/rcub_ibiss_994

Drakulić DR, Veličković N, Stanojlović, Milos  R, Grković IS, Mitrović N, Lavrnja I, Horvat AI. Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex. in Journal of Neuroendocrinology. 2013;25(7):125-616.
https://hdl.handle.net/21.15107/rcub_ibiss_994 .

Drakulić, Dunja R, Veličković, Nataša, Stanojlović, Milos  R, Grković, Ivana S, Mitrović, N, Lavrnja, Irena, Horvat, Anica I, "Low-Dose Dexamethasone Treatment Promotes the Pro-Survival Signalling Pathway in the Adult Rat Prefrontal Cortex" in Journal of Neuroendocrinology, 25, no. 7 (2013):125-616,
https://hdl.handle.net/21.15107/rcub_ibiss_994 .