24-hour-restraint stress induces long-term depressive-like phenotypes in mice.
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ABSTRACT:
SUBMITTER: Chu X
PROVIDER: S-EPMC5016966 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic stress is an important factor influencing people's health. It usually causes endocrinal disorders and a decline in reproduction in females. Although studies of both human and animals suggest a detrimental effect of stress on reproduction, the influence of chronic stress on the ovarian reservation and follicular development is still not clear. In this study, a chronic restraint stress (CRS) mouse model was used to investigate the effect of stress on ovarian reservation and follicular development and explore the underlying mechanism. In this study, after 8 weeks of CRS, primordial follicles were excessively activated in the ovaries of the CRS group compared with the control group. Further results showed that the activation of primordial follicles induced by CRS was involved in the increasing expression level of Kit ligand and its receptor Kit and the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) pathway. The corticotropin-releasing hormone (CRH) is a neuropeptide released due to stress, which plays an important role in regulating follicle development. A high level of serum CRH was detected in the CRS mouse model, and the real-time polymerase chain reaction assay showed that the mRNA level of its main receptor CRHR1increased in the ovaries of the CRS mouse group. Moreover, 100nM CRH significantly improved the activation of primordial follicles in newborn mouse ovaries in vitro. These results demonstrated that CRS could induce immoderate activation of primordial follicles accompanied by the activation of Kit-PI3K signaling, in which CRH might be an important endocrine factor.
| S-EPMC5877864 | biostudies-literature
Project description:ImportanceEvidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions.ObjectivesTo identify subgroups of older adults with similar 24-hour activity rhythm characteristics and characterize associated depression symptoms and cognitive performance.Design, setting, and participantsFrom January to March 2022, a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination and Survey (NHANES) accelerometer study was conducted. The NHANES used a multistage probability sample that was designed to be representative of noninstitutionalized adults in the US. The main analysis included participants 65 years or older who had accelerometer and depression measures weighted to represent approximately 32 million older adults.ExposuresLatent profile analysis identified subgroups with similar 24-hour activity pattern characteristics as measured using extended-cosine and nonparametric methods.Main outcomes and measuresCovariate-adjusted sample-weighted regressions assessed associations of subgroup membership with (1) depression symptoms defined as 9-Item Patient Health Questionnaire (PHQ-9) scores of 10 or greater (PHQ-9) and (2) having at least psychometric mild cognitive impairment (p-MCI) defined as scoring less than 1 SD below the mean on a composite cognitive performance score.ResultsThe actual clustering sample size was 1800 (weighted: mean [SD] age, 72.9 [7.3] years; 57% female participants). Clustering identified 4 subgroups: (1) 677 earlier rising/robust (37.6%), (2) 587 shorter active period/less modelable (32.6%), (3) 177 shorter active period/very weak (9.8%), and (4) 359 later settling/very weak (20.0%). The prevalence of a PHQ-9 score of 10 or greater differed significantly across groups (cluster 1, 3.5%; cluster 2, 4.7%; cluster 3, 7.5%; cluster 4, 9.0%; χ2 P = .004). The prevalence of having at least p-MCI differed significantly across groups (cluster 1, 7.2%; cluster 2, 12.0%; cluster 3, 21.0%; cluster 4, 18.0%; χ2 P < .001). Five of 9 depression symptoms differed significantly across subgroups.Conclusions and relevanceIn this cross-sectional study, findings indicate that approximately 1 in 5 older adults in the US may be classified in a subgroup with weak activity patterns and later settling, and approximately 1 in 10 may be classified in a subgroup with weak patterns and shorter active duration. Future research is needed to investigate the biologic processes related to these behavioral phenotypes, including why earlier and robust activity patterns appear protective, and whether modifying disrupted patterns improves outcomes.
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Project description:Depression is one of the most prevalent neuropsychiatric disorders in modern society. However, traditional drugs, such as monoaminergic agents, have defect showing lag response requiring several weeks to months. Additionally, these drugs have limited efficacy and high resistance rates in patients with depression. Thus, there is an urgent need to develop novel drugs or approaches for the treatment of depression. Here, using biochemical, pharmacological, genetic and behavioral methods, we demonstrate that metformin imparts a fast-acting antidepressant-like effect in naïve mice as well as stressed mice subjected to chronic restraint stress model. Moreover, inhibition of AMP-activated protein kinase (AMPK) activity by compound C or knock down of hippocampal AMPK? occluded the antidepressant-like effect induced by metformin. Our results suggest that metformin may be a viable therapeutic drug for the treatment of stress-induced depression via activation of AMPK.
| S-EPMC6961762 | biostudies-literature
Project description:Growing evidence has demonstrated that stress triggers gastrointestinal (GI) disorders. This study aimed to investigate how the acute cold water-immersion restraint (CWIR) stress affects intestinal injury and gut microbiota (GM) distribution. Male C57BL/6 mice were used to establish a CWIR animal model. Hematoxylin-eosin and periodic acid-Schiff staining were performed to assess intestinal histopathological changes. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and immunofluorescence staining were used to evaluate the expression of inflammatory cytokines and immune cell infiltration in the intestinal tissues. The gut permeability and intestinal occludin protein expression were determined through fluorescein isothiocyanate-dextran detection and western blot, respectively. GM profiles were analyzed via high-throughput sequencing of the fecal bacterial 16S rRNA genes. Results showed that CWIR induced more severe intestinal mucosal injury compared to the control, leading to a significant increase in tumor necrosis factor-α expression, but no infiltration of neutrophil and T cells. CWIR also resulted in GI disruption and increased the permeability of the intestinal mucosa. GM profiles showed that CWIR reduced GM diversity of mice compared with the control group. Specifically, aerobic and gram-negative bacteria significantly increased after CWIR, which was associated with the severity of gut injury under stress. Therefore, acute CWIR leads to severe intestinal damage with inflammation and disrupts the GM homeostasis, contributing to decreased GM diversity. Our findings provide the theoretical basis for the further treatment of intestinal disorders induced by CWIR.
| S-EPMC8551804 | biostudies-literature
Project description:OBJECTIVE:Previous studies found inconsistent results on the relationship between post-traumatic stress disorder (PTSD) and concentrations of 24-hour (24-h) urinary cortisol. This study performed a systematic review and meta-analysis to summarize previous findings on this relationship. METHODS:We searched in the databases of Web of Science, PubMed, Embase, and Psyc-ARTICLES for articles published before September 2018. We used the random-effects model with restricted maximum-likelihood estimator to synthesize the effect sizes by calculating the standardized mean difference (SMD) and assessing its significance. RESULTS:Six hundred and nineteen articles were identified from the preceding databases and 20 of them were included in the meta-analysis. Lower concentrations of 24-h urinary cortisol were observed in patients with PTSD when compared with the controls (SMD = -0.49, 95%CI [-0.91; -0.07], p = 0.02). Subgroup analysis revealed that the concentrations of 24-h urinary cortisol were lower in PTSD patients than in the controls for studies that included female participants or studies that included participants from the United States of America. CONCLUSIONS:Overall, decreased levels of 24-h urinary cortisol were linked with the pathophysiology of PTSD. Nonetheless, more studies should be conducted to validate the molecular underpinnings of urine cortisol degeneration in PTSD.
| S-EPMC6952249 | biostudies-literature
Project description:In vivo beta-cell neogenesis may be one way to treat diabetes. We aimed to investigate the effect of glucagon-like peptide-1 (GLP-1) on beta-cell neogenesis in type 2 diabetes mellitus (T2DM). Male C57BL/6J mice, 6 wk old, were randomly divided into three groups: Control, T2DM, and T2DM + Lira. T2DM was induced using high-fat diet and intraperitoneal injection of streptozotocin (40 mg/kg/d for 3 d). At 8 wk after streptozotocin injection, T2DM + Lira group was injected intraperitoneally with GLP-1 analog liraglutide (0.8 mg/kg/d) for 4 wk. Apparently for the first time, we report the appearance of a primitive bud connected to pancreas in all adult mice from each group. The primitive bud was characterized by scattered single monohormonal cells expressing insulin, GLP-1, somatostatin, or pancreatic polypeptide, and four-hormonal cells, but no acinar cells and ductal epithelial cells. Monohormonal cells in it were small, newborn, immature cells that rapidly proliferated and expressed cell markers indicative of immaturity. In parallel, Ngn3+ endocrine progenitors and Nestin+ cells existed in the primitive bud. Liraglutide facilitated neogenesis and rapid growth of acinar cells, pancreatic ducts, and blood vessels in the primitive bud. Meanwhile, scattered hormonal cells aggregated into cell clusters and grew into larger islets; polyhormonal cells differentiated into monohormonal cells. Extensive growth of exocrine and endocrine glands resulted in the neogenesis of immature pancreatic lobes in adult mice of T2DM + Lira group. Contrary to predominant acinar cells in mature pancreatic lobes, there were still a substantial number of mesenchymal cells around acinar cells in immature pancreatic lobes, which resulted in the loose appearance. Our results suggest that adult mice preserve the capacity of pancreatic neogenesis from the primitive bud, which liraglutide facilitates in adult T2DM mice. To our knowledge, this is the first time such a phenomenon has been reported.
| S-EPMC7563804 | biostudies-literature
Project description:Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of A? is considered to be the initial event. Thus, prevention of A? production would be an ideal strategy for the treatment or prevention of AD. A? is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, ? and ?-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor ?-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit A? production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased A? depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.
| S-EPMC3906130 | biostudies-literature
Project description:BackgroundStudies have indicated that depressive disorders are observed frequently in dentists. It's suggested that dentists encounter numerous sources of stress in their professional career. We noticed that the noises in dental environments are very unpleasant. The animal modeling studies suggested that stressful noise could produce depressive-like phenotypes in rodent animals. We hypothesize that the dental noise may be one of the primary stressors causing depressive disorders in dentists.ResultsWe treated C57BL/6 mice with programmatically played wide-spectrum dental noise for 8 h/day at 75?±?10 dB SPL level for 30 days, and then tested the behaviors. After exposure to dental noise, animals displayed the depressive-like phenotypes, accompanied by inhibition of neurogenesis in hippocampus. These deficits were ameliorated by orally administered with antidepressant fluoxetine.ConclusionsOur results suggested that dental noise could be one of the primary stressors for the pathogenesis of depressive disorders and the dental noise mouse model could be used in further depression studies.
| S-EPMC4894364 | biostudies-literature
Project description:Natural killer T (NKT) cells recognize glycolipid antigens presented by the MHC class I-related glycoprotein CD1d. The in vivo dynamics of the NKT cell population in response to glycolipid activation remain poorly understood. Here, we show that a single administration of the synthetic glycolipid alpha-galactosylceramide (alpha-GalCer) induces long-term NKT cell unresponsiveness in mice. NKT cells failed to proliferate and produce IFN-gamma upon alpha-GalCer restimulation but retained the capacity to produce IL-4. Consequently, we found that activation of anergic NKT cells with alpha-GalCer exacerbated, rather than prevented, B16 metastasis formation, but that these cells retained their capacity to protect mice against experimental autoimmune encephalomyelitis. NKT cell anergy was induced in a thymus-independent manner and maintained in an NKT cell-autonomous manner. The anergic state could be broken by IL-2 and by stimuli that bypass proximal TCR signaling events. Collectively, the kinetics of initial NKT cell activation, expansion, and induction of anergy in response to alpha-GalCer administration resemble the responses of conventional T cells to strong stimuli such as superantigens. Our findings have important implications for the development of NKT cell-based vaccines and immunotherapies.
| S-EPMC1193878 | biostudies-other
Project description:Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
2021-09-09 | GSE183624 | GEO