Effects of melatonin on behavior and BDNF-ERK-CREB signaling path-way in depression-like mice
10.3969/j.issn.1000-4718.2023.12.004
- VernacularTitle:褪黑素对小鼠抑郁样行为和BDNF-ERK-CREB信号通路的作用
- Author:
He YAN
1
,
2
;
Xiong LI
;
Jiameng DING
;
Dongxian ZHANG
Author Information
1. 昆明医科大学法医学院,云南 昆明 650500
2. 国家卫健委毒品依赖和戒治重点实验室,云南 昆明 650500
- Keywords:
depression;
melatonin;
fluoxetine;
BDNF-ERK-CREB signaling pathway
- From:
Chinese Journal of Pathophysiology
2023;39(12):2141-2149
- CountryChina
- Language:Chinese
-
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.
