Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor
| Autor: | Miroslav Adzic, Minja Milosavljevic, Emilija Glavonic, Zeljka Brkic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male medicine.medical_specialty Mitochondrial DNA Hypothalamo-Hypophyseal System Lipopolysaccharide Pituitary-Adrenal System Prefrontal Cortex Inflammation Apoptosis Glucocorticoid receptor Mitochondrion Biology Prefrontal cortex Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Receptors Glucocorticoid Internal medicine medicine Mitochondrial signaling Animals Phosphorylation Rats Wistar Depressive Disorder Major Depression General Neuroscience Mitochondria Rats Cytosol 030104 developmental biology Endocrinology chemistry Female Sex medicine.symptom Corticosterone 030217 neurology & neurosurgery Stress Psychological Signal Transduction |
| Zdroj: | Brain Research Bulletin |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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