Haojie Zhu, Jie Peng, Yunli Fang, Hanxiao Wang, Zhuo Chen, Wenfeng Hu, Lijuan Tong, Jie Ren, Chao Huang, Xu Lu
{"title":"在青少年慢性不可预测压力诱导的小鼠抑郁模型中,刺激小胶质细胞可产生类似抗抑郁的效果。","authors":"Haojie Zhu, Jie Peng, Yunli Fang, Hanxiao Wang, Zhuo Chen, Wenfeng Hu, Lijuan Tong, Jie Ren, Chao Huang, Xu Lu","doi":"10.1016/j.physbeh.2024.114782","DOIUrl":null,"url":null,"abstract":"<p><p>Depression triggered by harmful stress in adolescents is a common phenomenon that can lead to serious social problems. Its treatment is still frustrating in the clinic. We reported the phenomenon that a 12-day chronic unpredictable stress (CUS), starting on postnatal day 28, led to a significant decrease in the number of microglia in the dentate gyrus of the hippocampus in adult mice. Reversal of this decline by a single injection of low-dose lipopolysaccharide (LPS), a classical immunostimulant, could rapidly reverse the depression-like behaviors induced by 12 days of CUS stimulation during adolescence. In the dose-dependent experiment, a single injection of LPS at doses of 75 and 100 μg/kg, but not at doses of 25 and 50 μg/kg, produced an antidepressant effect in mice exposed to 12-day CUS during adolescence. The time-dependent experiment showed that the antidepressant effect of the single LPS injection (100 μg/kg) occurred at time points 5 and 8 hours, but not 3 hours after LPS injection. The antidepressant effect of the single LPS injection (100 μg/kg) lasted for at least 7 days, and 14 days after the single LPS injection, a repeated injection could still induce the depressed mice to develop an antidepressant phenotype. Furthermore, inhibition of microglia by minocycline or depletion of microglia by PLX3397 was found to prevent the antidepressant effect of the single LPS injection. These results suggest that reversing the decline of microglia in the dentate gyrus may be a potential strategy for the treatment of depression induced by harmful stress in adolescents.</p>","PeriodicalId":20201,"journal":{"name":"Physiology & Behavior","volume":" ","pages":"114782"},"PeriodicalIF":2.4000,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Microglia stimulation produces antidepressant-like effects in a mouse depression model induced by adolescent chronic unpredictable stress.\",\"authors\":\"Haojie Zhu, Jie Peng, Yunli Fang, Hanxiao Wang, Zhuo Chen, Wenfeng Hu, Lijuan Tong, Jie Ren, Chao Huang, Xu Lu\",\"doi\":\"10.1016/j.physbeh.2024.114782\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Depression triggered by harmful stress in adolescents is a common phenomenon that can lead to serious social problems. Its treatment is still frustrating in the clinic. We reported the phenomenon that a 12-day chronic unpredictable stress (CUS), starting on postnatal day 28, led to a significant decrease in the number of microglia in the dentate gyrus of the hippocampus in adult mice. Reversal of this decline by a single injection of low-dose lipopolysaccharide (LPS), a classical immunostimulant, could rapidly reverse the depression-like behaviors induced by 12 days of CUS stimulation during adolescence. In the dose-dependent experiment, a single injection of LPS at doses of 75 and 100 μg/kg, but not at doses of 25 and 50 μg/kg, produced an antidepressant effect in mice exposed to 12-day CUS during adolescence. The time-dependent experiment showed that the antidepressant effect of the single LPS injection (100 μg/kg) occurred at time points 5 and 8 hours, but not 3 hours after LPS injection. The antidepressant effect of the single LPS injection (100 μg/kg) lasted for at least 7 days, and 14 days after the single LPS injection, a repeated injection could still induce the depressed mice to develop an antidepressant phenotype. Furthermore, inhibition of microglia by minocycline or depletion of microglia by PLX3397 was found to prevent the antidepressant effect of the single LPS injection. These results suggest that reversing the decline of microglia in the dentate gyrus may be a potential strategy for the treatment of depression induced by harmful stress in adolescents.</p>\",\"PeriodicalId\":20201,\"journal\":{\"name\":\"Physiology & Behavior\",\"volume\":\" \",\"pages\":\"114782\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-12-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Physiology & Behavior\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.physbeh.2024.114782\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physiology & Behavior","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.physbeh.2024.114782","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Microglia stimulation produces antidepressant-like effects in a mouse depression model induced by adolescent chronic unpredictable stress.
Depression triggered by harmful stress in adolescents is a common phenomenon that can lead to serious social problems. Its treatment is still frustrating in the clinic. We reported the phenomenon that a 12-day chronic unpredictable stress (CUS), starting on postnatal day 28, led to a significant decrease in the number of microglia in the dentate gyrus of the hippocampus in adult mice. Reversal of this decline by a single injection of low-dose lipopolysaccharide (LPS), a classical immunostimulant, could rapidly reverse the depression-like behaviors induced by 12 days of CUS stimulation during adolescence. In the dose-dependent experiment, a single injection of LPS at doses of 75 and 100 μg/kg, but not at doses of 25 and 50 μg/kg, produced an antidepressant effect in mice exposed to 12-day CUS during adolescence. The time-dependent experiment showed that the antidepressant effect of the single LPS injection (100 μg/kg) occurred at time points 5 and 8 hours, but not 3 hours after LPS injection. The antidepressant effect of the single LPS injection (100 μg/kg) lasted for at least 7 days, and 14 days after the single LPS injection, a repeated injection could still induce the depressed mice to develop an antidepressant phenotype. Furthermore, inhibition of microglia by minocycline or depletion of microglia by PLX3397 was found to prevent the antidepressant effect of the single LPS injection. These results suggest that reversing the decline of microglia in the dentate gyrus may be a potential strategy for the treatment of depression induced by harmful stress in adolescents.
期刊介绍:
Physiology & Behavior is aimed at the causal physiological mechanisms of behavior and its modulation by environmental factors. The journal invites original reports in the broad area of behavioral and cognitive neuroscience, in which at least one variable is physiological and the primary emphasis and theoretical context are behavioral. The range of subjects includes behavioral neuroendocrinology, psychoneuroimmunology, learning and memory, ingestion, social behavior, and studies related to the mechanisms of psychopathology. Contemporary reviews and theoretical articles are welcomed and the Editors invite such proposals from interested authors.