Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor.

Mitochondrial signaling in inflammation-induced depressive behavior in female and male rats: The role of glucocorticoid receptor. Brain Res Bull. 2019 Jun 25;150:317-327 Authors: Brkic Z, Milosavljevic M, Glavonic E, Adzic M 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 intr...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research