| Background: Major depressive disorder(MDD)is a mood disorder characterized by persistent depression,slow thinking and reduced movement.Treatment-resistant depression(TRD)becomes a more difficult problem in clinical treatment due to its poor therapeutic effect of clinical antidepressants,long latent cycle and easy relapse.Therefore,it is necessary to further explore the etiology and pathogenesis of depression.It has been reported that White Matter(WM)was damaged in the prefrontal cortex,internal capsule and corpus callosum in patients with depression.Abnormal changes of oligodendrocytes and myelin were also observed in depressive animal models.In CNS,hemoglobin subunit beta(Hbb)is expressed in neurons and oligodendrocyte lineage cells,and decreased in the chronic unpredictable mild stress(CUMS)depression animal models.Hbb-b1 in neurons may regulate energy metabolism and participate in the occurrence of diseases.However,the effects of Hbb-b1 in oligodendrocyte lineage cells and the occurrence of depression remain unclear.Purpose:To elucidate the effect of Hbb-b1 expressed in oligodendrocyte lineage cells on the occurrence of depression and its mechanism.Methods:We used C57BL/6J mice to establish CUMS depression model and weighed weekly,after 12 weeks,the behavioral tests of the sucrose preference,tail suspension,forced swimming,open field,elevated plus maze test were performed.Immunohistochemical staining(IHC)assessed OL numbers in corpus callosum.The expressions of myelin basic protein(MBP)and Hbb-b1 in corpus callosum were detected by Western Blot.The changes of myelin in corpus callosum were observed by transmission electron microscopy,and abnormal myelin ratio and G-ratio(axon diameter/total myelin diameter)were analyzed.In vitro experiments,lentivirus transfection was used to establish Hbb-b1 knockdown stable OLN-93 cell lines,and immunofluorescence,marking and IGF-1 methods were used to investigate the effects of Hbb-b1 on the morphology,migration and differentiation of OLN-93 cells.The experimental results were expressed as Mean ± SEM,and P< 0.05 indicated a significant difference in statistical resultsResults:(1)Established the CUMS depressive mouse model successfully.(2)The quantity of OL,the expressions of MBP and Hbb-b1 in corpus callosum of CUMS mice was significantly decreased.(3)Compared with CTL,the G-ratio of myelin sheath,the proportion of abnormal myelin sheath was increased in the corpora callosum of CUMS mice,and pathological changes occur in the myelin sheath.(4)Lentivirus transfected OLN-93 cells to knock down Hbb-b1,and WB proved successfully.Hbb-b1 KD affects the morphology of OLN-93 cells before and after differentiation.(5)Hbb-b1 KD affects the migration,differentiation and maturation of OLN-93 cells.Conclusions:Hbb-b1 may be involved in the occurrence of MDD by influencing myelin regeneration. |
