Unpredictable chronic Mild stress paradigm established effect of pro- and anti-inflammatory cytokine on neurodegeneration-linked depressive states in Hamsters with Brain endothelial damages

Themechanismsbywhichinflammationaffectsthe different emotional moods are only partially known. Previous works have pointed to stress hormones like glucocorticoids plus the vascular factor endothelin-1 as key factors evoking stressful states especially in relation to endothelial dysfunctions. With this work, it was our intention to establish the role of pro- and anti-inflammatory cytokine expression variations towards depression-like behaviors and consequently the developmentofneurodegenerationeventscausedbyendothelial damages in the hamster (Mesocricetus auratus). Such a rodent, which is considered a valuable animal model to test depression and anxiety states, exhibited a variety of depression-like behaviors including reduction in sucrose consumption, locomotion, and exploration (p < 0.01) following exposure to unpredictable chronic mild stress. Contextually, a tight correlation between unpredictable chronic mild stressinduced depressive states and expression of the proinflammatory cytokines was detected as shown by marked expression levels (p < 0.01) of IL-1β and NF-kB in the hippocampus, amygdala, and prefrontal cortex. Even the antiinflammatory cytokine IL-10 supplied notably significant (p < 0.001) expression levels in the same areas of resilienthamsters. Application of hemodynamic and endothelial functionalstudiespointedtoalteredarterialendothelialactivitiesin depressed withrespect to resilient animals.Moreover, evident damagedneuronalfieldsintheaboveareasofdepressedhamstersallowedustocorrelatesuchabehavioralphenomenonto the upregulation of IL-1β and NF-κB. Overall, the differing roles of pro- and anti-inflammatory cytokines on depressive states, especially in view of brain endothelial damages, may provide novel therapeutic measures against mood disorders linked to neurodegenerative diseases.