Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor
Само за регистроване кориснике
2019
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Mitochondrial dysfunction can result from the interplay between elevated inflammatory markers and alterations in hypothalamic–pituitary–adrenal (HPA) axis, and can contribute to pathogenesis of major depression. Therefore, in this study we investigated whether the effects of lipopolysaccharide (LPS) on glucocorticoid receptor (GR) could be associated with alterations in mitochondrial apoptotic signaling in the prefrontal cortex of male and female Wistar rats with depressive-like behavior. To that end, we measured LPS-induced alterations in the extrinsic and intrinsic apoptotic pathways in mitochondria and cytosol of PFC of female and male rats, as well as the levels of cleaved cytosolic PARP-1. We also measured the mitochondrial levels of GR and its phosphoisoforms pGR232 and pGR246, as well as the mRNA levels of two GR-regulated mitochondrial genes, COX-1 and COX-3. We discovered that although seven-day LPS treatment evoked depressive-like behavior and induced apoptosis in the PFC of ...both sexes, it affected apoptotic cascades in both sexes differently. In females the treatment initiated both intrinsic and extrinsic apoptotic cascade, while in males only intrinsic cascade was engaged. Alterations in intrinsic apoptotic pathway were more associated with GR alterations in males, where LPS treatment decreased levels of mitochondrial GR and increased pGR232/pGR246 ratio. Alterations in mitochondrial GR could be associated with changes in expression of genes involved in oxidative metabolism in the PFC of this sex, and could, in combination with elevated levels of BCL-2 and decreased levels of BAX detected in this cell fraction, mitigate the detrimental effect of LPS on mitochondria in male PFC. © 2019
Кључне речи:
Mitochondrial signaling / Lipopolysaccharide / Sex / Glucocorticoid receptor / Prefrontal cortexИзвор:
Brain Research Bulletin, 2019, 150, 317-327Финансирање / пројекти:
- Дефинисање кластера молекулских биомаркера за побољшану дијагностику и терапију поремећаја расположења (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41029)
DOI: 10.1016/j.brainresbull.2019.06.016
ISSN: 0361-9230; 1873-2747
PubMed: 31251961
WoS: 000477784800034
Scopus: 2-s2.0-85067838805
Институција/група
VinčaTY - JOUR AU - Brkić, Željka AU - Milosavljević, Minja AU - Glavonić, Emilija AU - Adžić, Miroslav PY - 2019 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8359 AB - Mitochondrial dysfunction can result from the interplay between elevated inflammatory markers and alterations in hypothalamic–pituitary–adrenal (HPA) axis, and can contribute to pathogenesis of major depression. Therefore, in this study we investigated whether the effects of lipopolysaccharide (LPS) on glucocorticoid receptor (GR) could be associated with alterations in mitochondrial apoptotic signaling in the prefrontal cortex of male and female Wistar rats with depressive-like behavior. To that end, we measured LPS-induced alterations in the extrinsic and intrinsic apoptotic pathways in mitochondria and cytosol of PFC of female and male rats, as well as the levels of cleaved cytosolic PARP-1. We also measured the mitochondrial levels of GR and its phosphoisoforms pGR232 and pGR246, as well as the mRNA levels of two GR-regulated mitochondrial genes, COX-1 and COX-3. We discovered that although seven-day LPS treatment evoked depressive-like behavior and induced apoptosis in the PFC of both sexes, it affected apoptotic cascades in both sexes differently. In females the treatment initiated both intrinsic and extrinsic apoptotic cascade, while in males only intrinsic cascade was engaged. Alterations in intrinsic apoptotic pathway were more associated with GR alterations in males, where LPS treatment decreased levels of mitochondrial GR and increased pGR232/pGR246 ratio. Alterations in mitochondrial GR could be associated with changes in expression of genes involved in oxidative metabolism in the PFC of this sex, and could, in combination with elevated levels of BCL-2 and decreased levels of BAX detected in this cell fraction, mitigate the detrimental effect of LPS on mitochondria in male PFC. © 2019 T2 - Brain Research Bulletin T1 - Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor VL - 150 SP - 317 EP - 327 DO - 10.1016/j.brainresbull.2019.06.016 ER -
@article{ author = "Brkić, Željka and Milosavljević, Minja and Glavonić, Emilija and Adžić, Miroslav", year = "2019", abstract = "Mitochondrial dysfunction can result from the interplay between elevated inflammatory markers and alterations in hypothalamic–pituitary–adrenal (HPA) axis, and can contribute to pathogenesis of major depression. Therefore, in this study we investigated whether the effects of lipopolysaccharide (LPS) on glucocorticoid receptor (GR) could be associated with alterations in mitochondrial apoptotic signaling in the prefrontal cortex of male and female Wistar rats with depressive-like behavior. To that end, we measured LPS-induced alterations in the extrinsic and intrinsic apoptotic pathways in mitochondria and cytosol of PFC of female and male rats, as well as the levels of cleaved cytosolic PARP-1. We also measured the mitochondrial levels of GR and its phosphoisoforms pGR232 and pGR246, as well as the mRNA levels of two GR-regulated mitochondrial genes, COX-1 and COX-3. We discovered that although seven-day LPS treatment evoked depressive-like behavior and induced apoptosis in the PFC of both sexes, it affected apoptotic cascades in both sexes differently. In females the treatment initiated both intrinsic and extrinsic apoptotic cascade, while in males only intrinsic cascade was engaged. Alterations in intrinsic apoptotic pathway were more associated with GR alterations in males, where LPS treatment decreased levels of mitochondrial GR and increased pGR232/pGR246 ratio. Alterations in mitochondrial GR could be associated with changes in expression of genes involved in oxidative metabolism in the PFC of this sex, and could, in combination with elevated levels of BCL-2 and decreased levels of BAX detected in this cell fraction, mitigate the detrimental effect of LPS on mitochondria in male PFC. © 2019", journal = "Brain Research Bulletin", title = "Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor", volume = "150", pages = "317-327", doi = "10.1016/j.brainresbull.2019.06.016" }
Brkić, Ž., Milosavljević, M., Glavonić, E.,& Adžić, M.. (2019). Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor. in Brain Research Bulletin, 150, 317-327. https://doi.org/10.1016/j.brainresbull.2019.06.016
Brkić Ž, Milosavljević M, Glavonić E, Adžić M. Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor. in Brain Research Bulletin. 2019;150:317-327. doi:10.1016/j.brainresbull.2019.06.016 .
Brkić, Željka, Milosavljević, Minja, Glavonić, Emilija, Adžić, Miroslav, "Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor" in Brain Research Bulletin, 150 (2019):317-327, https://doi.org/10.1016/j.brainresbull.2019.06.016 . .