中国病理生理杂志2023，Vol.39Issue(12)：2141-2149,9.DOI:10.3969/j.issn.1000-4718.2023.12.004
褪黑素对小鼠抑郁样行为和BDNF-ERK-CREB信号通路的作用
Effects of melatonin on behavior and BDNF-ERK-CREB signaling path-way in depression-like mice
摘要
Abstract
AIM:To investigate the effect of melatonin(MEL)on the depression behavior in mice induced by chronic restraint stress(CRS).METHODS:Forty-eight SPF-grade male C57BL/6J mice were randomly divided into con-trol group(n=12)and CRS group(n=36).The mice in CRS group were further divided into 3 groups(n=12):CRS+vehi-cle group,CRS+fluoxetine(FLX)group,and CRS+MEL group.Mouse depression model was established by the CRS method for 14 d,and then the depression-like behaviors were observed for modeling validation.After 14 d of drug interven-tion combined with CRS,the behaviors were detected again.Nissl staining,RT-qPCR,Western blot and immunofluores-cence staining were performed in mouse brain tissues.RESULTS:Compared with control group,the weight changes of the mice in CRS group were significantly lowered,the immobility time of forced swimming and tail suspension tests was sig-nificantly increased,the consumption rate of sugar water decreased significantly,and the central time and movement dis-tance in open-field test decreased significantly(P＜0.01).Compared with CRS+vehicle group,the depression-like behaviors induced by CRS were successfully reversed by the drugs in both CRS+FLX and CRS+MEL groups.Furthermore,com-pared with CRS+vehicle group,the mRNA levels of brain-derived neurotrophic factor(BDNF),extracellular signal-regulated kinase(ERK)and cAMP response element-binding protein(CREB),and the protein levels of BDNF,phosphorylated ERK1/2 and CREB were increased significantly in both CRS+FLX and CRS+MEL groups(P＜0.01).The results of Nissl staining showed that the neurons in CRS+vehicle group were irregularly arranged,and the number of Nissl bodies was de-creased(P＜0.01).The neuron status and number of Nissl bodies in both CRS+FLX and CRS+MEL groups were signifi-cantly improved(P＜0.01).Immunofluorescence staining showed that the number of c-Fos-positive cells in the frontal cor-tex and hippocampal CA1 region of the mice in CRS+vehicle group was significantly larger than that in control group(P＜0.01).Conversely,the number of c-Fos-positive cells in CRS+FLX and CRS+MEL groups was significantly smaller than that in CRS+vehicle group(P＜0.01).CONCLUSION:Melatonin can significantly alleviate depression-like behavior in-duced by CRS in mice,which may be related to the activation of BDNF-ERK-CREB signaling pathway.关键词
抑郁症/褪黑素/氟西汀/BDNF-ERK-CREB信号通路Key words
depression/melatonin/fluoxetine/BDNF-ERK-CREB signaling pathway分类
医药卫生引用本文复制引用
严赫,李雄,丁佳萌,张冬先..褪黑素对小鼠抑郁样行为和BDNF-ERK-CREB信号通路的作用[J].中国病理生理杂志,2023,39(12):2141-2149,9.基金项目
云南省科技厅项目(No.202301AY070001-262) （No.202301AY070001-262）
