Effects of nootkatone on depression-like behavior and PKA/CREB/BDNF signaling pathway in hippocampus
10.19405/j.cnki.issn1000-1492.2022.05.010
- Author:
Kaixin Wang
1
,
2
;
Sanwang Wang
3
;
Qingling Zhai
4
;
Di Zhao
1
,
5
;
Jing Liu
1
,
5
;
Fantao Meng
1
,
5
;
Chen Li
1
,
5
;
Jinbo Chen
4
Author Information
1. Institute for Metabolic &
2. Neuropsychiatric Disorders ,Dept of Neurology,Binzhou Medical University Hospital ,Binzhou 256603
3. Dept of Psychology,Binzhou Medical University Hospital ,Binzhou 256603
4. Dept of Neurology,Binzhou Medical University Hospital ,Binzhou 256603
5. Neuropsychiatric Disorders ,Binzhou Medical University Hospital ,Binzhou 256603
- Publication Type:Journal Article
- Keywords:
depression;
chronic unpredictable stress;
nootkatone;
neurogenesis;
brain⁃derived neurotrophic factor
- From:
Acta Universitatis Medicinalis Anhui
2022;57(5):725-730
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effects of nootkatone on depression-like behavior, neurogenesis and protein kinase A(PKA)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF) signaling pathway in hippocampus of chronic unpredictable stress(CUS) treated mice, and to explore the role and molecular mechanism of nootkatone′s antidepressant effect.
Methods:Male C57 BL/6 mice were randomly divided into 3 groups: the control group(saline), the CUS group(CUS+saline), the CUS+nootkatone group(CUS+nootkatone). The sucrose preference test and forced swim test were used to evaluate the depression-like behaviors. The mRNA expression of BDNF in hippocampus was measured by RTPCR. The expression levels of BDNF, PKA and phosphorylated cyclic adenosine monophosphate response element-binding protein(p-CREB) in hippocampus were determined by Western blot. The level of neurogenesis was measured by immunofluorescence.
Results:Compared with the control group, the sucrose preference decreased(P<0.05) and the latency decreased(P<0.05), and immobility time increased in forced swim test(P<0.05) in CUS group, the expression levels of BDNF mRNA(P<0.05) and protein(P<0.05), PKA(P<0.05) and p-CREB(P<0.05) decreased. The sucrose preference of the CUS+nootkatone group increased(P<0.05) and the latency increased(P<0.05), and immobility time decreased in forced swim test(P<0.05), the expression levels of BDNF mRNA(P<0.05) and protein(P<0.05), PKA(P<0.05) and p-CREB(P<0.05) increased in comparison with the CUS group. Compared with control group, the number of hippocampal doublecortin(DCX) labeled neurons decreased(P<0.05) in CUS group. Compared with the CUS group, the number of DCX labeled neurons increased in the CUS+nootkatone group(P<0.05).
Conclusion:The improvement of depressive symptoms in CUS mice by nootkatone may be related to the neurogenesis in dentate gyrus of hippocampus and the activation of PKA/CREB/BDNF signaling pathway.
- Full text:2025021915232384795诺卡酮对抑郁样行为和海马中...B_BDNF信号通路的影响_王凯新.pdf
