Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation
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Аутори
Velickovic, NatasaDrakulić, Dunja R.
Petrovic, Snjezana
Grković, Ivana
Milošević, Maja
Stanojlović, Miloš R.
Horvat, Anica
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Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 be...ta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.
Кључне речи:
HPA axis / Inflammation / Rat brain / IrradiationИзвор:
Cellular and Molecular Neurobiology, 2012, 32, 7, 1175-1185Финансирање / пројекти:
- Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (RS-MESTD-Basic Research (BR or ON)-173044)
DOI: 10.1007/s10571-012-9843-1
ISSN: 0272-4340
PubMed: 22527859
WoS: 000309234700011
Scopus: 2-s2.0-84867583030
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Институција/група
VinčaTY - JOUR AU - Velickovic, Natasa AU - Drakulić, Dunja R. AU - Petrovic, Snjezana AU - Grković, Ivana AU - Milošević, Maja AU - Stanojlović, Miloš R. AU - Horvat, Anica PY - 2012 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5051 AB - Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction. T2 - Cellular and Molecular Neurobiology T1 - Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation VL - 32 IS - 7 SP - 1175 EP - 1185 DO - 10.1007/s10571-012-9843-1 ER -
@article{ author = "Velickovic, Natasa and Drakulić, Dunja R. and Petrovic, Snjezana and Grković, Ivana and Milošević, Maja and Stanojlović, Miloš R. and Horvat, Anica", year = "2012", abstract = "Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary-adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time-course changes of serum corticosterone level, as well IL-1 beta and TNF-alpha level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NF kappa B) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NF kappa B mRNA and protein in the hippocampus at 1 h. The increment in NF kappa B protein persisted for 2 h, therefore NF kappa B/GR protein ratio was turned in favor of NF kappa B. Central inflammation was characterized by increased IL-1 beta in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1 beta and TNF-alpha were undetectable in the serum. Enhanced hypothalamic IL-1 beta probably induced the relocation of hippocampal NF kappa B to the nucleus and decreased NF kappa B mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.", journal = "Cellular and Molecular Neurobiology", title = "Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation", volume = "32", number = "7", pages = "1175-1185", doi = "10.1007/s10571-012-9843-1" }
Velickovic, N., Drakulić, D. R., Petrovic, S., Grković, I., Milošević, M., Stanojlović, M. R.,& Horvat, A.. (2012). Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation. in Cellular and Molecular Neurobiology, 32(7), 1175-1185. https://doi.org/10.1007/s10571-012-9843-1
Velickovic N, Drakulić DR, Petrovic S, Grković I, Milošević M, Stanojlović MR, Horvat A. Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation. in Cellular and Molecular Neurobiology. 2012;32(7):1175-1185. doi:10.1007/s10571-012-9843-1 .
Velickovic, Natasa, Drakulić, Dunja R., Petrovic, Snjezana, Grković, Ivana, Milošević, Maja, Stanojlović, Miloš R., Horvat, Anica, "Time-Course of Hypothalamic-Pituitary-Adrenal Axis Activity and Inflammation in Juvenile Rat Brain After Cranial Irradiation" in Cellular and Molecular Neurobiology, 32, no. 7 (2012):1175-1185, https://doi.org/10.1007/s10571-012-9843-1 . .