| There are many different hypotheses about depression.In recent years,the Monocyte-T-Lymfocyte hypothesis believes that excessively activated macrophages and lymphocytes secrete too much leukocyte factor and the immune response can stimulate the hypothalamic-pituitary-adrenal(HPA)axis,Leading to excessive secretion of glucocorticoids(GC),activation of microglia through corticotropin-releasing factor receptor 2(CRFR2),causing the release of neuroinflammation and reactive oxygen species,causing neuronal damage and loss of neurotransmitters,And eventually led to depression.It is known that when peripheral inflammation is activated,high concentrations of interleukin-6(IL-6)and low concentrations of transforming growth factor-β(TGF-β)together induce T helper cell 17(Th17)differentiation to produce the proinflammatory factor interleukin-17A(IL-17A),exacerbating peripheral inflammation.Studies show that IL-17 A can change the permeability of the blood-brain barrier,making IL-17 A and Th17 infiltrate the central nervous sysytem(CNS)when inflammation occurs.It is newly found that there are also lymphatic vessels in the brain,and there are IL-17 A receptors on the surface of microglia,suggesting that Th17 cells secrete IL-17 A and cause central inflammation.It is known that when neuroinflammation occurs,excessive activation of microglia can produce excessive IL-6,and neuroinflammation can cause the decrease of TGF-β secreted by astrocytes,which creates favorable conditions for the differentiation of Th17 in the central.In the pathogenesis of experimental autoimmune encephalomyelitis(EAE),Th17 and IL-17 A participated in the neuroinflammation of the disease,and IL-17 A increased the neuroinflammation of EAE by activating glial cell surface receptors.It shows that Th17 and IL-17 A can participate in neuroinflammation of brain disease.Another clinical trial on psoriasis(an autoimmune disease caused by IL-17)proved that after treatment with IL-17 inhibitors,the depressive symptoms of patients with psoriasis complicated by depression also improved,Indicating that IL-17 may be involved in the occurrence of depression.Studies have shown that when depression occurs,the differentiation of Th17 cells and the concentration of IL-17 in the periphery are positively correlated with the degree of depression.However,in the neuroinflammation of depression,the changes of Th17 cells and IL-17 A,and their relationship with microglia,neurotransmitters,and behavioral changes have not been studied.Because the pathogenesis of depression is complicated and the side effects of drugs are significant,it is very important to explore the pathogenesis of depression and find natural drugs with high efficiency and low side effects.As a natural health food,sea cucumber has the functions of anti-tumor and immune regulation,while sea cucumber phospholipids as the main component of the body wall of sea cucumber has the effects of anti-oxidative stress,neuroprotective effect and memory improvement.The therapeutic effect of sea cucumber phospholipids on depression has not been reported.According to the above introduction,this study raises the key question: In the brain of depression model,can IL-6 and TGF-β induce Th17 cell differentiation and secrete IL-17 A,IL-17 A in the neuroinflammation of depression,and what is the role of depression-related behaviors and pathological changes? Can sea cucumber phospholipids achieve antidepressant effects by improving the immune function of Th17-Treg cells?Therefore,this experiment selects the Chronic Unpredictable Mild Stress(CUMS)model to explore the related changes of IL-17 A in the neuroinflammation of depression,and the intervention effect of sea cucumber phospholipids on depression.Method:1.In this experiment,the CUMS-induced model was selected as the object of depression research,which was treated by gavage with sea cucumber phospholipid(50,100 mg / kg / day);2.Depression-and anxiety-like behavior induced by chronic stress was tested by sucroce preference,elevated plus maze,“open field”,tail suspension;3.High performance liquid chromatography(HPLC)was used to detect the content of neurotransmitters and metabolites in the cerebral cortex and hippocampus;4.RT-PCR and ELISA was used to detect the concentration of GC in the peripheral blood,the concentration of neuroinflammation factors,the expression of Th17 and Treg cells transcription factors and IL-17 A receptors,and the activation of microglia in the hippocampus;Result:1.Stress caused a significant decrease in mice’s sucroce preference,the number and time of exploration of the open arms in elevated plus maze,the exploration ability and activity of the “open field”,and the latency of the closed arms in elevated plus maze and the totalimmobility increased significantly.Sea cucumber phospholipids(100 mg / kg)has a significant improvement effect;2.Stress caused a significant decrease in the content of serotonin(5-HT)and dopamine(DA)in the cerebral cortex and hippocampus of mice,and a significant increase of.metabolites pentahydroxyindoleacetic acid(5-HIAA)and dihydroxyphenylacetic acid(DOPAC),the 5-HT / 5-HIAA ratio and DA / DOPAC ratio were significantly reduced.Sea cucumber phospholipids(100 mg / kg)has a significant improvement effect;3.Stress caused excessive release of peripheral GC in mice,IL-6,IL-23,IL-17 A,STAT3,Ro Ra,IL-17 RA,IL-17 RC in CNS all increased significantly,the expression of Iba-1 in the hippocampus increased,TGF-β significantly reduced,sea cucumber phospholipids(100 mg / kg)has a certain improvement effect;Conclusion:1.Sea cucumber phospholipids inhibit the release of proinflammatory factors IL-6,IL-17 A,IL-23,inhibit the expression of Th17 cell transcription factors STAT3,Ro Ra,reduce the expression of IL-17 RC,and inhibit the microglia Iba-1 expression,increase TGF-β expression and improve CUMS-induced depression-like behaviors and loss of neurotransmitters;2.The cause of IL-17 involvement in neuroinflammation may be that stress induces Th17 differentiation,and excess IL-17 A produced activates glial cell surface receptors IL-17 RA and IL-17 RC,causing an increase in the proinflammatory phenotype of microglia,neuroinflammation that exacerbates depression;... |
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