Mouse Model Of Chronic Stress Research Articles

GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.

Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

Antidepressant potential of total flavonoids from Astragalus in a chronic stress mouse model: Implications for myelination and Wnt/β-catenin/Olig2/Sox10 signaling axis modulation

Ethnopharmacological relevanceRadix Astragali, a versatile traditional Chinese medicinal herb, has a rich history dating back to “Sheng Nong's herbal classic”. It has been employed in clinical practice to address various ailments, including depression. One of its primary active components, total flavonoids from Astragalus (TFA), remains unexplored in terms of its potential antidepressant properties. This study delves into the antidepressant effects of TFA using a mouse model subjected to chronic unpredictable mild stress (CUMS). Aims of the studyThe study aimed to scrutinize how TFA influenced depressive behaviors, corticosterone and glutamate levels in the hippocampus, as well as myelin-related protein expression in CUMS mice. Additionally, it sought to explore the involvement of the Wnt/β-catenin/Olig2/Sox10 signaling axis as a potential antidepressant mechanism of TFA. Materials and methodsMale C57BL/6 mice were subjected to CUMS to induce depressive behaviors. TFA were orally administered at two different doses (50 mg/kg and 100 mg/kg). A battery of behavioral tests, biochemical analyses, immunohistochemistry, UPLC-MS/MS, real-time PCR, and Western blotting were employed to evaluate the antidepressant potential of TFA. The role of the Wnt/β-catenin/Olig2/Sox10 signaling axis in the antidepressant mechanism of TFA was validated through MO3.13 cells. ResultsTFA administration significantly alleviated depressive behaviors in CUMS mice, as evidenced by improved sucrose preference, reduced immobility in tail suspension and forced swimming tests, and increased locomotor activity in the open field test. Moreover, TFA effectively reduced hippocampal corticosterone and glutamate levels and promoted myelin formation in the hippocampus of CUMS mice. Then, TFA increased Olig2 and Sox10 expression while inhibiting the Wnt/β-catenin pathway in the hippocampus of CUMS mice. Finally, we further confirmed the role of TFA in promoting myelin regeneration through the Wnt/β-catenin/Olig2/Sox10 signaling axis in MO3.13 cells. ConclusionsTFA exhibited promising antidepressant effects in the CUMS mouse model, facilitated by the restoration of myelin sheaths and regulation of corticosterone, glutamate, Olig2, Sox10, and the Wnt/β-catenin pathway. This research provides valuable insights into the potential therapeutic application of TFA in treating depression, although further investigations are required to fully elucidate the underlying molecular mechanisms and clinical relevance.

Niuhuang Qingxin Wan ameliorates depressive-like behaviors and improves hippocampal neurogenesis through modulating TrkB/ERK/CREB signaling pathway in chronic restraint stress or corticosterone challenge mice.

Introduction: Chronic stress-associated hormonal imbalance impairs hippocampal neurogenesis, contributing to depressive and anxiety behaviors. Targeting neurogenesis is thus a promising antidepressant therapeutic strategy. Niuhuang Qingxin Wan (NHQXW) is an herbal formula for mental disorders in Traditional Chinese Medicine (TCM) practice, but its anti-depressant efficacies and mechanisms remain unverified. Methods: In the present study, we tested the hypothesis that NHQXW could ameliorate depressive-like behaviors and improve hippocampal neurogenesis by modulating the TrkB/ERK/CREB signaling pathway by utilizing two depression mouse models including a chronic restraint stress (CRS) mouse model and a chronic corticosterone (CORT) stress (CCS) induced mouse model. The depression-like mouse models were orally treated with NHQXW whereas fluoxetine was used as the positive control group. We evaluated the effects of NHQXW on depressive- and anxiety-like behaviors and determined the effects of NHQXW on inducing hippocampal neurogenesis. Results: NHQXW treatment significantly ameliorated depressive-like behaviors in those chronic stress mouse models. NHQXW significantly improved hippocampal neurogenesis in the CRS mice and CCS mice. The potential neurogenic mechanism of NHQXW was identified by regulating the expression levels of BDNF, TrkB, p-ERK (T202/T204), p-MEK1/2 (S217/221), and p-CREB (S133) in the hippocampus area of the CCS mice. NHQXW revealed its antidepressant and neurogenic effects that were similar to fluoxetine. Moreover, NHQXW treatment revealed long-term effects on preventing withdrawal-associated rebound symptoms in the CCS mice. Furthermore, in a bioactivity-guided quality control study, liquiritin was identified as one of the bioactive compounds of NHQXW with the bioactivities of neurogenesis-promoting effects. Discussion: Taken together, NHQXW could be a promising TCM formula to attenuate depressive- and anxiety-like behaviors against chronic stress and depression. The underlying anti-depressant mechanisms could be correlated with its neurogenic activities by stimulating the TrkB/ERK/CREB signaling pathway.

A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

ObjectiveTo explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced (LPS-induced) depression mouse model. MethodsWe created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections. The mice were divided into the following groups: control, model, fluoxetine, Tiansi Yin, Sini powder, and low-, medium-, and high-dose Peiyuan Jieyu formula groups. Forced swim and tail suspension tests were used to assess the efficacy of the depression (despair) model, and weight gain rates were also measured. Furthermore, serum levels of various depression and inflammation-associated molecules, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), tryptophan, 5-hydroxytryptamine, kynurenine (KYN), and kynurenic acid (KA) were assessed. Furthermore, the expression levels of ionic calcium-binding adaptor molecule-1 (IBA-1) and indoleamine 2,3-dioxygenase (IDO) mRNA in hippocampal microglia were measured. ResultsThe model group displayed greater despair-associated immobility, which was shortened in response to various doses of Peiyuan Jieyu formula. Furthermore, formula administration significantly reduced serum TNF-α levels and hippocampal IDO mRNA expression. The high formula dose also reduced IFN-γ and IBA-1 levels, the latter was also decreased in response to the medium formula dose. However, the low formula dose reduced serum KYN level and KYN/tryptophan (TRP) and KYN/KA ratios. ConclusionThe Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model, potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Protective Effects of Lacticaseibacillus rhamnosus IDCC3201 on Motor Functions and Anxiety Levels in a Chronic Stress Mouse Model.

Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.

Tong-Xie-Yao-Fang promotes dendritic cells maturation and retards tumor growth in colorectal cancer mice with chronic restraint stress

Ethnopharmacological relevanceDepression is one of the important risk factors that accelerate the progression of colorectal cancer (CRC). Tong-Xie-Yao-Fang (TXYF) is a widely used classical formula for treating psychiatric-related intestinal diseases in traditional Chinese medicine, that is composed of four different herbs: Atractylodes macrocephala Koidz. (Baizhu), Paeonia lactiflora Pall. (Baishaoyao), Citrus reticulata Blanco (Chenpi), Saposhnikovia divaricata (Turcz.) Schischk (Fangfeng). TXYF has over a hundred years of history and can significantly improve depression and reduce intestinal symptoms. However, the intervention effect and mechanism of TXYF on colorectal cancer accompanied by psychological stress are not still clear. Aim of studyThis study investigated the therapeutic effect of TXYF on CRC mice with chronic restraint stress (CRS) and to explore its mechanism. Materials and methodsWe constructed a mouse model of chronic stress by CRS and subcutaneous injection of CT26-Luc cells, and administered TXYF by gavage. We measured the body weight, tumor size, and tumor weight of each group of mice. The tumor growth was monitored dynamically of by vivo bioluminescence analysis. The depressive state of each group of mice were evaluated by tail suspension test, forced swimming test, and hormone level changes. We used flow cytometry to detect the ratio of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, and dendritic cells (DCs) phenotype (MHC II, CD80, and CD86) and chemotaxis ability (CXCR4 and CCR7) of in peripheral blood and tumor tissue. the levels of IL-12, IL-18, Th1 cytokines, and Th2 cytokines in the serum of each group of mice were determined by ELISA. ResultsTXYF can improve the body weight of CRC mice with CRS, inhibit tumor volume and weight, alleviate depressive state, upregulate 5-HT levels, and inhibit HPA axis hormone secretion. The results of flow cytometry showed that TXYF can promote the maturation of DCs phenotype and function, enhance antigen presentation ability, increase the ratio of CD4+ T cells and CD4+/CD8+ T cells, and shift Th1/Th2 balance towards Th1 cells, thus increasing serum levels of IFN-γ, IL-18, IL-2, and IL-12, while decreasing serum levels of IL-4 and IL-10, and effectively triggering T cell-mediated immune response. ConclusionsThis study shows that TXYF inhibits the growth of tumors in CRC mice with CRS by stimulating immune response. The mechanism may be inhibiting the HPA axis and promoting DCs maturation, thus activating T cells and enhancing anti-tumor immune response, ultimately preventing the progression of CRC.

Melatonin-related dysfunction in chronic restraint stress triggers sleep disorders in mice.

Stress may trigger sleep disorders and are also risk factors for depression. The study explored the melatonin-related mechanisms of stress-associated sleep disorders on a mouse model of chronic stress by exploring the alteration in sleep architecture, melatonin, and related small molecule levels, transcription and expression of melatonin-related genes as well as proteins. Mice undergoing chronic restraint stress modeling for 28days showed body weight loss and reduced locomotor activity. Sleep fragmentation, circadian rhythm disorders, and insomnia exhibited in CRS-treated mice formed sleep disorders. Tryptophan and 5-hydroxytryptamine levels were increased in the hypothalamus, while melatonin level was decreased. The transcription and expression of melatonin receptors were reduced, and circadian rhythm related genes were altered. Expression of downstream effectors to melatonin receptors was also affected. These results identified sleep disorders in a mice model of chronic stress. The alteration of melatonin-related pathways was shown to trigger sleep disorders.

Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress.

Chronic stress is a risk factor for Major Depressive Disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side-effects. This study investigated the activity profiles and behavioral efficacy of two enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and separately reduces immobility in the forced swim test and improves stress-induced spatial working memory deficits. Using unpredictable chronic mild stress (UCMS), we show that acute and chronic administration of GL-RM provide pro-cognitive effects, with mild efficacy on mood symptoms, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.

Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression

Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated over the last decades and very little progress has been made to improve the efficiency of current therapeutic approaches. In order to better understand the disease, it is necessary for researchers to use appropriate animal models that reproduce specific aspects of the complex clinical manifestations at the behavioral and molecular levels. Here, we review the current literature describing the use of mouse models to reproduce specific aspects of MDD and anxiety in males and females. We first describe some of the most commonly used mouse models and their capacity to display unique but also shared features relevant to MDD. We then transition toward an integral description, combined with genome-wide transcriptional strategies. The use of these models reveals crucial insights into the molecular programs underlying the expression of stress susceptibility and resilience in a sex-specific fashion. These studies performed on human and mouse tissues establish correlates into the mechanisms mediating the impact of stress and the extent to which different mouse models of chronic stress recapitulate the molecular changes observed in depressed humans. The focus of this review is specifically to highlight the sex differences revealed from different stress paradigms and transcriptional analyses both in human and animal models.

P.0800Pro-cognitive effects of a Nociceptin/orphaninFQ receptor antagonist in a mouse model of chronic stress

P.0800Pro-cognitive effects of a Nociceptin/orphaninFQ receptor antagonist in a mouse model of chronic stress

Vitamin A5/X controls stress-adaptation and prevents depressive-like behaviors in a mouse model of chronic stress

9-cis-13,14-dihydroretinoic acid (9CDHRA), acts as an endogenous ligand of the retinoid X receptors (RXRs), and is an active form of a suggested new vitamin, vitamin A5/X. Nutritional-relevance of this pathway as well as its detailed role in vertebrate physiology, remain largely unknown. Since recent GWAS data and experimental studies associated RXR-mediated signaling with depression, we explored here the relevance of RXR and vitamin A5/X-mediated signaling in the control of stress adaptation and depressive-like behaviors in mice. We found that compromised availability of 9CDHRA in Rbp1−/− mice was associated with increased despair in the forced swim and anhedonia in the sucrose preference test. 9CDHRA similarly to synthetic RXR agonist, BMS649, normalized despair behaviors in Rbp1−/− but not Rxrγ−/− mice, supporting involvement of RXR signaling in anti-despair activity of these ligands. Importantly, similarly to BMS649, the 9CDHRA and its nutritional-precursor, 9-cis-13,14-dihydroretinol (vitamin A5/X alcohol), prevented development of depressive-like behaviors in mice exposed to chronic social defeat stress, revealing the beneficial role of RXRs and its endogenous ligand in stress adaptation process. These data point to the need for relevant nutritional, biochemical and pharmacological studies of this signaling pathway in human, both in physiological conditions and in pathologies of stress-related disorders.

Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes.

This study aimed to examine the effects of Lactobacillus plantarum, a lactic acid bacteria strain isolated from kimchi, on the development of low-grade inflammation and type 2 diabetes mellitus (T2DM) exacerbated by chronic stress. C57BL/6 mice were fed either a high-fat diet (HFD) and randomized into an HFD group or a group that was fed an HFD and subjected to chronic cold exposure-related stress (HFDS), or mice were fed a normal diet (ND) and randomized into an ND group or a group that was fed an ND and subjected to chronic cold exposure-related stress (NDS). Lactobacillus plantarum LRCC5310 (108, 1010 CFU) and LRCC5314 (108, 1010 CFU) as well as L. gasseri BNR17 (108 CFU), as a positive control, were administered orally twice every day to all the mice for 12 weeks. The expression of Glut4 and adiponectin, main glucose transporter-related genes, was upregulated in the LRCC5310- and LRCC5314-treated groups. Levels of serum proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) and of mRNAs of proinflammatory genes (Tnf-α, Il-6, Ccl2, leptin) were elevated in HFDS mice. The expression of proinflammatory genes was downregulated in LRCC5310- and LRCC5314-treated groups; this was not the case for Tnf-α expression in HFDS mice. Levels of serum corticosterone and mRNA levels of stress-related genes (Npy, Y2r) were decreased in lactic acid bacteria (LAB)-fed groups, with only LRCC5314 downregulating Npy expression in HFDS mice. These results suggest that the LAB strains can normalize the expression of metabolic genes, inhibit inflammatory responses, and suppress stress in HFDS mice.

Chronic Febuxostat Treatments Prevents Cerebrovascular Dysfunction Associated with Chronic Stress

Chronic stress is a risk factor for many cerebrovascular diseases including stroke and vascular dementia. Our lab has previously shown that chronic stress impairs cerebrovascular function potentially mediated by an increase in oxidative stress driven by the xanthine oxidase pathway. However, the therapeutic avenues of the xanthine oxidase inhibitor, febuxostat have yet to be examined in the context of chronic stress induced cerebrovascular dysfunction. Here, we examined the effect of chronic febuxostat treatment on middle cerebral artery function in a mouse model of chronic stress. At 18 weeks of age, mice underwent the unpredictable chronic mild stress (UCMS; 5 days/weeks for 7hrs/day) paradigm to elicit a chronic stress phenotype; simultaneously, drinking water was treated with febuxostat (50mg/L) and provided to mice ad libitum (n=9-10/group). On week 26 mice were euthanized and the middle cerebral arteries (MCA) were removed and positioned in a pressurized myobath. To test for vessel health, the MCA was exposed to increasing concentrations of acetylcholine (Ach; 10-9M to 10-4M), phenylephrine (PE; 10-9M to 10-4M), and sodium nitroprusside (SNP; 10-9M to 10-4M). Consistent with previous work, mice exposed to chronic stress with no treatment displayed impaired MCA dilation to Ach compared to controls (8.4±0.8um to 19.7±0.8um, respectively; p<0.0001). Interestingly, mice exposed to chronic stress while simultaneously treated with febuxostat displayed comparable MCA dilation to Ach compared to controls (18.6±0.4um to 19.7±0.8um, respectively; n.s.). There were no differences found between groups in response to PE or SNP. These data suggest that the cerebrovascular dysfunction associated with chronic stress may be driven by increased xanthine oxidase activity.

Positive Allosteric Modulation at α5-GABAA Receptor Reverses Cognitive Dysfunctions and Neuronal Atrophy in Mouse Model of Chronic Stress

Altered GABA/somatostatin (SST) signaling is frequently reported in psychiatric diseases and chronic stress models, participating in symptom emergence. SST+ interneurons from cortical layers and the hippocampus inhibit the dendrites of excitatory neurons, largely through α5-containing GABAA receptors (α5-GABAA-R). Recently, we showed that targeting α5-GABAA-R alleviates symptoms and exerts neurotrophic effects in old mice. Here, we propose to investigate the behavioral and neurotrophic effects of the same compound, combined with its enantiomer, in an animal model of chronic stress.

Characterization of proinflammatory markers in the ventral tegmental area across mouse models of chronic stress

Despite the high prevalence of major depressive disorder (MDD), understanding of the biological underpinnings remains limited. Rodent models suggest that changes in activity and output of dopamine (DA) neurons in the ventral tegmental area (VTA) are important for depressive-like phenotypes. Additionally, brain inflammatory processes are thought to contribute to MDD pathology and inflammation in the VTA has been linked to changes in VTA DA neuronal activity. Thus, we sought to determine whether there is increased inflammatory signaling in the VTA following forms of chronic stress that induce depressive-like symptoms. First, we subjected male mice to either physical or vicarious chronic social defeat stress (CSDS), paradigms known to induce long-term depressive-like behavior and changes in VTA signaling. Second, we subjected male and female mice to subchronic variable stress (SCVS), a paradigm that induces depressive-like behavior only in female mice. We then isolated mRNA from the VTA and assessed proinflammatory gene regulation via RT-PCR. Our results show that physical, but not vicarious, CSDS increases interleukin 1β (IL-1β) mRNA expression and this inversely correlates with social interaction score. In contrast, IL-1β expression was unchanged in male or female mice following SCVS. No significant increases in VTA ionized calcium binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) immunochemistry were detected following CSDS that would be indicative of a robust inflammatory response. In conclusion, we show that chronic stressors distinctively alter expression of proinflammatory genes in the VTA and changes may depend on the severity and time-course of the stress exposure.

Protective Effects of Milk Casein on the Brain Function and Behavior in a Mouse Model of Chronic Stress.

Chronic stress is a major cause of mental health problems and primary medical issues. Milk has been studied for its stress-reducing effects. Tryptophan, which is abundant in milk, is a precursor of the neuroactive compounds serotonin and melatonin. This study investigated the preventive effects of milk casein on brain dysfunction and anxiety-like behavior induced by chronic stress. Mice were exposed to unpredictable chronic mild stress (UCMS) and milk casein was administered for 10 weeks. Milk casein significantly reduced stress-induced changes in serum corticosterone and serotonin levels. The negative effects of UCMS on the expression of proteins associated with neuroendocrine function, neurodegeneration, neuronal inflammation, and barrier function of the blood-brain barrier were statistically normalized by casein treatment. Pretreatment with casein significantly prevented anxiety-like behavior induced by UCMS. These results suggest that milk casein has the potential to prevent stress-induced brain dysfunction and anxiety-like behavior.

Antidepressant effect of buddleja cordata methanolic extract in chronic stress mouse model

Background: Preclinical studies in animal models have shown anti-inflammatory, analgesic, antioxidant, and neuroprotective effects of B. cordata. Objectives: To explore the antidepressant effect of a methanolic extract of Buddleja cordata leaves (MEBc) in early maternal separation and chronic restraint stress mouse model. Materials and Methods: From day 2 to day 21, the litters were removed from the maternal cage for 3h/day. Based on the pharmacological treatments, four experimental groups were established: sham animals without maternal separation, chronic restrained stress and oral administration (S group) or 10 ml/Kg/day saline solution (SS group) or 100 mg/kg/day of MEBc (MEBc group) or 20 mg/kg/day of fluoxetine (F group). After 4 weeks of these treatments the antidepressant activity was evaluated through behavioral tests and also IL-6 determinations were performed. Results: Mice administered with MEBc showed significantly diminished immobility time in the forced swimming test (P < 0.01), tail suspension test (P < 0.001) and the time spent in the open arm of the elevated plus-maze (P < 0.01) versus SS group. By contrast, animals treated with fluoxetine only diminished immobility time in the tail suspension test (P < 0.01). The vegetal extract was more effective (P < 0.05) that fluoxetine in preventing the increase of interleukin 6 (IL-6) over the hippocampus and prefrontal cortex region (45 and 20 %, respectively). Conclusion: These results demonstrate the antidepressant and anxiolytic effects of MEBc over the chronic stress depression-induced model.

A method to establish a chronic restraint stress mouse model with colorectal cancer xenografts

Colorectal cancer (CRC) remains one of the most common clinical cancers of digestive tract. Recently, a large number of researches have shown that chronic stress can actively participate in the development of CRC. The proposed method successfully established the model of chronic stress mouse model with colorectal cancer.•Chronic restraint stress (CRS) was used to establish chronic stress model.•CRS was combined with a colorectal cancer xenografts model.•Behavioural tests and tumour growth were used to evaluate model construction.

Adult neurogenesis augmentation attenuates anhedonia and HPA axis dysregulation in a mouse model of chronic stress and depression

Major depressive disorder is a common debilitating mental health problem that represents one of the leading causes of disability. Up to date, the therapeutic targets and approaches are still limited. Adult hippocampal neurogenesis (AHN) has been proposed as a critical contributor to the pathophysiology and treatment of depression, altering the hippocampal control over stress response at network, neuroendocrine and behavioral levels. These findings together have suggested that manipulating AHN may be a promising therapeutic strategy for depression. To investigate this question, we assessed whether increasing adult neurogenesis would be sufficient to produce antidepressant-like effects at behavioral and neuroendocrine levels in a mouse model of depression; the unpredictable chronic mild stress (UCMS). For this purpose, we used a bi-transgenic mouse line (iBax) in which AHN increase was induced by deletion of the pro-apoptotic gene Bax from the neural progenitors following the tamoxifen-dependent action of CreERT2 recombinases. UCMS induced a syndrome that is reminiscent of depression-like states, including anhedonia (cookie test), physical changes (coat deterioration, reduced weight gain), anxiety-like behaviors (higher latency in the novelty-supressed feeding –NSF– test), passive stress-coping behaviors (immobility in the forced swim test –FST–) and a blunted hypothalamo-pituitary-adrenal (HPA) axis reactivity to acute stress in addition to AHN decrease. Tamoxifen injection reversed the AHN decrease as well as partly counteracted UCMS effects on the cookie test and HPA axis but not for the coat state, weight gain, NSF test and FST. Taken together, our results suggest that a strategy directing at increasing AHN may be able to alleviate some depression-related behavioral and neuroendocrine dimensions of UCMS, such as anhedonia and HPA axis reactivity deficits, but may be hardly sufficient to produce a complete recovery.