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Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice.

ABSTRACT: The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.

SUBMITTER: Kim J

PROVIDER: S-EPMC7805143 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice.

Kim Jinho J Suh Yoo-Hun YH Chang Keun-A KA

Molecular brain 20210113 1

The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative ...[more]

PMID: 33441182

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Project description:The depression-like behavior phenotype, neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy. The present study aimed to clarify the dynamic changes of depression-like behavior, dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment. Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors, including white noise, thermal swimming, stroboscopic illumination, soiled cages, pairing with three other stressed animals, cold swimming, tail pinch, restraint and water and food deprivation. Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group (normal feeding without any stressors). To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression, a sucrose preference test was used to evaluate the degree of anhedonia. An open-field test was used to evaluate locomotor activity and anxiety status. Compared with the control group, chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks. Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks. In addition, chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling. To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression, markers (DCX and DCX/BrdU) of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence. Compared with the control group, neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks; however, neural proliferation and differentiation in the dentate gyrus decreased, and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group. Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression. The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group. These findings indicate that during chronic unpredictable mild stress-induced depression, the behavioral phenotype, miR-124 expression in the hippocampus, neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes, which suggested that various pathological changes occur at different stages of depression. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.

Project description:IntroductionTo inform tobacco policy and prevention efforts, we examined youth and young adult behaviors at gas-station-convenience stores and whether these behaviors varied by demographics or tobacco use.Aims and methodsBetween June and July 2017, we conducted 990 intercept surveys at convenience stores in North Carolina among 16- to 25-year olds who were susceptible to or used tobacco. We used logistic regression to examine whether demographics or tobacco use predicted pumping gas, entering the store, or purchasing tobacco, gas, food, lottery tickets, or other items inside the store.ResultsMost participants (85.3%) reported ever using tobacco. Most visited that store at least once per week (40.3%) or once within the past month (41.2%). Just over half (55.0%) reported pumping gas at the store. Of those who went or planned to go inside (68.8%), 43.2% purchased food, 39.2% purchased gas, 33.1% purchased tobacco, and 6.8% purchased lottery tickets. Those who were aged 21-25, visited the store two to three times a week, and went inside already were more likely to purchase tobacco (all p < .05). Past 30-day cigarette, cigar, smokeless, and other tobacco uses were positively associated with purchasing tobacco (all p < .05).ConclusionsOur sample of young people who were susceptible to or ever used tobacco regularly visited gas-station-convenience stores, and one-third purchased or planned to purchase tobacco during their visit. Convenience stores appear to be an important access point for young people. Practitioners and policy makers should consider a comprehensive set of strategies to reduce access among youth and young adults.ImplicationsWe conducted 990 intercept surveys among youth and young adults at gas-station-convenience stores. Among our sample of those who had ever used tobacco or were susceptible to use, most visited the store frequently and one-third purchased tobacco, particularly those who used cigarettes and cigars. Tobacco companies heavily market in convenience stores, and our results show tobacco is a product often purchased by susceptible young adults. Practitioners and policy makers should consider prioritizing efforts at convenience stores to reduce product purchase and use.

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Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice.

Publications

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice.

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