Chronic Stress Induces Inflammatory Response And Microglial Remodeling In Rat Prefrontal Cortex

Aim: This study aims to explore:1.whether the chronic psychological stress and pain stress can induces depressive behavior and pain threshold in rats by two kinds of chronic stress models,the chronic unpredictable mild stress model and spared nerve injury model;2.the impact of chronic psychological stress and chronic pain stress on the expression of pro-inflammatory cytokinesin in prefrontal cortex;3.the impact of chronic psychological stress and chronic pain stress on microglia’s morphological structure in prefrontal cortex.4.whether the changes of expression of pro-inflammatory cytokinesin in prefrontal cortex have laterality.5.whether the changes in microglia have laterality.Methods: Male Sprague-Dawley were randomly divided into control group,chronic psychological stress group,sham group and chronic pain stress group for5 weeks chronic stress.After that,the weight was measured,and then open field test,sucrose preference test and pain threshold was detected.After the behavior tests,RTPCR was used for exploring the levelof pro-inflammatory cytokines in prefrontal cortex(IL-1β,IL-6,TNF-α).The morphological structure of microglia in prefrontal cortex were also observed by confocal microscopy and analysed the cell body perimeter,branch points,total process length,number of processes originating from soma,and convex hull area.Results: 1.chronic psychological stress and chronic pain stress induced depressive behavior and declined the pain threshold.In weight gain,comparing to control,chronic psychological stress showed significant less weight gain.In open field test,chronic psychological stress group showed significant decline in travel distance,central crossing frequencyand number of rearingthan control,also chronic pain stress group had significant decrese in travel distance,central crossing frequency and number of rearing than sham.In sucrose preference test,rats in chronic psychological stress group showed significant less sucrose preference than control and rats in chronic pain stress group had significant less sucrose preference than sham.2.In pain threshold test,rats in chronic psychological stress group had significant lower mechanical withdrawal threshold(50%MWT)than control both left and right and rats in chronic pain stress group had significant lower mechanical withdrawal threshold than sham in left.3.chronic psychological stress and chronic pain stress made the change of proinflammatory cytokines in rats prefrontal cortex.Rats in chronic psychological stress group had significant higher level of IL-1β and TNF-α than control,rats in chronic pain stress group had significant higher level of IL-1β 、 IL-6 than sham.4.chronic psychological stress and chronic pain stress made the structural re-organization of microglia in prefrontal cortex.the expression of Iba-1 in chronic psychological stress group and chronic pain group were activated.Conclusion: 1.the behavior change are non-specific under chronic stress;2.the mechanism of chronic stress in central nervous system is manifested as inflammation in the prefrontal cortex of rats,where il-1β is an important regulator of inflammatory response;3.the activation of microglia as structural re-organization is a important marker of chronic stress comorbidity in rat prefrontal cortex;4.there are no laterality in prefrontal cortex inflammatory reaction and microglia’s structural re-organization.