Effects of SR9009 and LXH0225,REV-ERB agonists,on mood disor-ders and cognitive impairment in over-training mice
10.3867/j.issn.1000-3002.2024.11.002
- VernacularTitle:REV-ERB激动剂SR9009和LXH0225对过度训练所致小鼠情感障碍和认知损伤的改善作用
- Author:
Qi DENG
1
,
2
;
Xinhua HE
;
Zhiyong XIAO
;
Wenxia ZHOU
Author Information
1. 南京中医药大学,江苏 南京 210023
2. 军事医学研究院国家安全特需药品全国重点实验室,北京 100850
- Keywords:
SR9009;
LXH0225;
forced swimming;
mood disorder;
cognitive impairment
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(11):816-825
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the effects of SR9009 and LXH0225,nuclear receptor subfamily 1 group D member(REV-ERB)agonists,on mood disorders and cognitive impairment in over-training mice.METHODS Male C57BL/6J mice were randomly divided into the normal control,over-training model,model+fluoxetine(15 mg?kg-1),model+SR9009(100 mg?kg-1)and model+LXH0225(50 mg?kg-1)groups.Mice in the normal control group were ip given15%cremophor without extra stress while those in other groups were ip given 15%cremophor or different drugs respectively 30 min before daily forced swimming stress.When stressed,mice were forced to swim in 19-21℃water for 20 min per day for 18 d.After that,locomotor activity was assessed.Rotarod test and weight-loaded swimming test were performed to measure physical strength,while open field test and stair-climbing test were performed to measure anxiety-like behavior.Tail suspension test and forced swimming test were used to measure depression-like behavior while novel object recognition test and Y maze test were conducted to measure recogni-tion function.ELISA was used to measure serum corticosterone contents.RESULTS Compared with the normal control group,the locomotor activity of mice in the model group was significantly increased(P<0.01).There were anxiety-like behaviors with a significant increase in the number of times of stair-climb-ing and rearing(P<0.01).Depression-like behaviors were observed with a significant increase immobile time in forced swimming test(P<0.01).Cognitive impairment was manifested as decreased accuracy of Y-maze spontaneous alternation response(P<0.01).The corticosterone content was significantly elevated(P<0.01)in forced swimming mice.Compared with the model group,the accuracy of Y-maze spontaneous alternations was higher(P<0.01)and the content of serum corticosterone was lower(P<0.01)in the model+fluoxetine group.The immobile time was shorter(P<0.01),the spontaneous alternation response of Y maze was was less accurate(P<0.05)and serum corticosterone content was lower(P<0.01)in the model+SR9009 group than in the model group.The latency to fall off the rotarod was longer(P<0.05),the immobile time was shorter(P<0.01)and the content of serum corticosterone was lower(P<0.01)in the model+LXH0225 group compared with the model group.CONCLUSION The REV-ERBs agonists SR9009 and LXH0225 may protect against forced swimming over-training induced mood disorders and cognitive impairment.
