| Chronic stress leads to various mental illnesses,and its pathogenesis is mainly related to abnormal regulation of the hypothalamic-pituitary-adrenal(HPA)axis.Recent studies suggest that stress potentiates neuroinflammation of the central nervous system.Polysaccharide-protein complex of Lycium barbarum L.(LbGp),as an active component of Lycium barbarum L.(Goji berry),has immunomodulatory effects.This study thus investigates the neuroinflammatory response of the medial prefrontal cortex(mPFC)driven by chronically physical restraint stress,in addition to the role of LbGp in relieving anxiety-like behaviors via regulating neuroinflammation.Using 7-day physical restraint stress,we found that mice had increased anxiety levels,which were associated with abnormal dendritic formation in pyramidal neurons of mPFC.Oral application of LbGp significantly relieved stress-induced anxiety and dendritic abnormalities.Using transcriptomics approach,the anxiolytic effect of LbGp may be related to the alleviation of neuroinflammation,which is further confirmed by the identification of microglia activation in mPFC.In addition,we found that chronic stress significantly reduced serum levels of glucocorticoids,whereas LbGp can restore normal glucocorticoids in stressed animals.More importantly,the infusion of glucocorticoid receptor antagonist RU486 deprived anxiolytic and anti-neuroinflammatory effects of LbGp.Those results collectively suggest that chronic stress may increase anxiety levels by promoting local neuroinflammation of mPFC,and LbGp can effectively alleviate neuroinflammation and anxiety in mice by activating glucocorticoid receptor-related pathways.Our results discover potential anxiolytic effects of LbGp as active ingredients of Goji berry,in addition to possible mechanisms of alleviation on neuroinflammation. |
