Effects Of Chronic Restraint Stress Research Articles

The Effect of Chronic Restraint Stress Induced Alzheimer Like Changes In Male Adult Rats

Abstract Chronic stress has become a common problem that cannot be ignored and has become an important risk factor for the onset of many diseases. Responses to chronic stress are systemic reactions involving multiple organs and can induce symptoms such as depression, cognitive impairment, cardiovascular disease, immune dysfunctions, impaired reproductive ability, bone loss, and reduced life expectancy. Aim The present study was designed to investigate the effect of chronic restraint stress on the cognitive function in male albino rats, further to demonstrate its relation to amyloid and tau protein accumulation. Methods 24-albino male wistar rats were divided into 2 groups as Control group and Chronic restraint stress (CRS) subjected group (done by restraining rats for 3 hours daily for 4 weeks). Body weight, morris water maze test (MWM) and brain levels of p tau and amyloid beta were investigated Results CRS increased body weight significantly in week 4 and increased latency time as observed in MWM test compared to control group. Additionally, p tau and amyloid beta levels in CRS group were significantly increased. Conclusion chronic stress is able to accelerate the appearance of Alzheimer’s disease (AD) Changes upon chronic stress in the brain were related to accumulation of β-amyloid, TAU hyperphosphorylation in males.

Sex-Dependent Effects of Chronic Restraint Stress on Mood-Related Behaviours and Neurochemistry in Mice.

Anxiety and depressive disorders are closely associated; however, the pathophysiology of these disorders remains poorly understood. Further exploration of the mechanisms involved in anxiety and depression such as the stress response may provide new knowledge that will contribute to our understanding of these disorders. Fifty-eight 8-12-week-old C57BL6 mice were separated into experimental groups by sex as follows: male controls (n = 14), male restraint stress (n = 14), female controls (n = 15) and female restraint stress (n = 15). These mice were taken through a 4-week randomised chronic restraint stress protocol, and their behaviour, as well as tryptophan metabolism and synaptic proteins, were measured in the prefrontal cortex and hippocampus. Adrenal catecholamine regulation was also measured. The female mice showed greater anxiety-like behaviour than their male counterparts. Tryptophan metabolism was unaffected by stress, but some basal sex characteristics were noted. Synaptic proteins were reduced in the hippocampus in stressed females but increased in the prefrontal cortex of all female mice. These changes were not found in any males. Finally, the stressed female mice showed increased catecholamine biosynthesis capability, but this effect was not found in males. Future studies in animal models should consider these sex differences when evaluating mechanisms related to chronic stress and depression.

Effect of chronic restraint stress on body weight of male Sprague Dawley rats

Effect of chronic restraint stress on body weight of male Sprague Dawley rats

Effects of chronic restraint stress in the prostate of prepubertal and adult rats.

To investigate the effects of chronic stress in the prostate of prepubertal and adult rats. Thirty-two male rats were assigned into four groups depending on the type of treatment (control or stressed) and the age at which stress was initiated (prepubertal or adult). Restraint stress stimuli were applied for six weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimuli were named SP and SA groups, respectively. Age-matched rats were used as control groups (CP and CA). At the end of the experiment, the rats were euthanized, and prostate morphological parameters were evaluated and statistically compared. Application of stress stimuli to the SP group resulted in reduced body weight, but no prostate morphological modification was noted. The SA group showed reduced testosterone level and prostatic epithelium surface density, in comparison to CA group. Further, the prostatic lumen surface density was increased in adult stressed animals, in comparison to adult controls. The stress stimuli promoted changes in hormonal and morphological parameters in the prostate of adult stressed rats. Prepubertal stressed animals did not presented modifications of prostate morphology.

Chronic restraint stress impairs voluntary wheel running but has no effect on food-motivated behavior in mice

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed that exposure of mice to 2-hour daily restraint sessions for 14 to 16 days during the light phase of the cycle reliably decreased voluntary wheel running but had no effect on working for food in a fixed ratio 10 schedule of food reinforcement or in a progressive ratio schedule of food reinforcement. This dissociation between the two types of behavioral activities could reflect an adaptive response to the constraint imposed by chronic restraint stress on mitochondria function and its negative consequences on energy metabolism. To determine whether it is the case, we administered mesenchymal stem cells intranasally to chronically restrained mice to repair the putative mitochondrial dysfunction induced by chronic restraint stress. This intervention had no effect on wheel running deficits. Assessment of mitochondrial gene expression in the brain of mice submitted to chronic restraint stress revealed an increase in the expression of genes involved in mitochondrial biology that showed habituation with repetition of daily sessions of restraint stress. These original findings can be interpreted to indicate that chronic restraint stress induces behavioral and mitochondrial adjustments that contribute to metabolic adaptation to this stressor and maintain metabolic flexibility.

Effects of Chronic Restraint Stress on Apoptosis of Amygdala Cells in Rats.

To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model. The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry. Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group. This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.

Effect of chronic restraint stress and western‐diet feeding on colonic regulatory gene expression in mice

AbstractBackgroundDiet‐induced obesity (DIO) and psychological stress are significant independent regulators of gastrointestinal physiology; however, our understanding of how these two disorders influence the host‐microbe interface is still poorly characterized. The aim of this study was to assess the combined influences of diet‐induced obesity and psychological stress on microbiome composition and colonic gene expression.MethodsC57BL/6J mice (n = 48) were subject to a combination of 22 weeks of Western diet (WD) feeding and a chronic restraint stressor (CRS) for the last 4 weeks of feeding. At the end of the combined intervention, microbiome composition was determined from cecal contents, and colonic tissue gene expression was assessed by multiplex analysis using NanoString nCounter System and real‐time qPCR.ResultsWD feeding induced a DIO phenotype with increased body weight, worsened metabolic markers, and alterations to microbiome composition. CRS reduced body weight in both dietary groups while having differential effects on glucose metabolism. CRS improved the Firmicutes/Bacteroidetes ratio in WD‐fed animals while expanding the Proteobacteria phyla. Significantly lower expression of colonic Tlr4 (p = 0.008), Ocln (p = 0.004), and Cldn3 (p = 0.004) were noted in WD‐fed animals compared to controls with no synergistic effects observed when combined with CRS. No changes to colonic expression of downstream inflammatory mediators were observed. Interestingly, higher levels of expression of Cldn2 (p = 0.04) and bile acid receptor Nr1h4 (p = 0.02) were seen in mice exposed to CRS.ConclusionDifferential but not synergistic effects of WD and CRS were noted at the host‐microbe interface suggesting multifactorial responses that require further investigation.

The effects of chronic restraint stress on empathy-like behaviour in rats

It is clearly known that psychological stress is an important threat to health in today's modern societies. Recent studies have shown that acute stress causes an increase in positive social behaviours such as prosocial behaviour and devotion which are components of empathic behaviour. Neuropsychiatric manifestations such as anxiety and depression may affect empathic behaviour. The aim of this study was to investigate the effects of chronic restraint stress on empathy-like behaviour and the histopathological changes in the amygdala, prefrontal cortex in the adrenal glands and thymus, as well as the neurochemical pathways associated with empathy, oxytocin and vasopressin. The chronic stress group was subjected to restraint stress daily for 14 days after all subjects were trained to rescue its stressed cagemate using empathy test equipment for 12 days. It was observed that chronic restraint stress had no effect on empathy-like behaviour in rats. Vasopressin levels in amygdala was increased in chronic stress group compared to control group. Anxiety and depression indicators did not change in both groups. In the open field test, control group spent more time in thigmo zone compared to chronic stress group. Adrenal glands relative weights and apoptotic cell ratios were significantly higher in the chronic stress group compared to the control group (expectedly). Although there was no significant difference in behavioral tests, histopathological changes were detected. In subsequent studies, it is appropriate to examine the effects of different types of stress applications, gender-related changes, and other neurochemical pathways associated with stress and empathy.

White Matter Changes Following Chronic Restraint Stress and Neuromodulation: A Diffusion Magnetic Resonance Imaging Study in Young Male Rats

BackgroundRepetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation technique, is an effective treatment for depression. However, few studies have used diffusion magnetic resonance imaging to investigate the longitudinal effects of rTMS on the abnormal brain white matter (WM) described in depression. MethodsIn this study, we acquired diffusion magnetic resonance imaging from young adult male Sprague Dawley rats to investigate 1) the longitudinal effects of 10- and 1-Hz low-intensity rTMS (LI-rTMS) in healthy animals; 2) the effect of chronic restraint stress (CRS), an animal model of depression; and 3) the effect of 10 Hz LI-rTMS in CRS animals. Diffusion magnetic resonance imaging data were analyzed using tract-based spatial statistics and fixel-based analysis. ResultsSimilar changes in diffusion and kurtosis fractional anisotropy were induced by 10- and 1-Hz stimulation in healthy animals, although changes induced by 10-Hz stimulation were detected earlier than those following 1-Hz stimulation. Additionally, 10-Hz stimulation increased axial and mean kurtosis within the external capsule, suggesting that the two protocols may act via different underlying mechanisms. Brain maturation–related changes in WM, such as increased corpus callosum, fimbria, and external and internal capsule fiber cross-section, were compromised in CRS animals compared with healthy control animals and were rescued by 10-Hz LI-rTMS. Immunohistochemistry revealed increased myelination within the corpus callosum in LI-rTMS–treated CRS animals compared with those that received sham or no stimulation. ConclusionsOverall, decreased WM connectivity and integrity in the CRS model corroborate findings in patients experiencing depression with high anxiety, and the observed LI-rTMS–induced effects on WM structure suggest that LI-rTMS might rescue abnormal WM by increasing myelination.

Chronic restraint stress induces anxiety-like behavior and remodeling of dendritic spines in the central nucleus of the amygdala

Previous studies have shown that the anxiogenic effects of chronic stress do not correlate with dendritic remodeling in the central nucleus of the amygdala (CeA). We analyzed the effect of chronic restraint stress (CRS; 20 min/day for 14 days), relative to control (CTRL) conditions on anxiety-like behavior in the elevated plus maze (EPM) and the open field tests, and dendritic morphology, dendritic spine density and spine type numbers in pyramidal neurons of the CeA. Reversal of CRS-induced effects was explored in animals allowed a 14-day stress-free recovery after treatments. CRS decreased the frequency and time in the open arms and increased the anxiety index in the EPM, and reduced visits and time in the center of the open field. Morphological assays in these animals revealed no effect of CRS on dendritic complexity in CeA neurons; however, a decrease in dendritic spine density together with decreased and increased amounts of mushroom and thin spines, respectively, was detected. Subsequent to a stress-free recovery, a significant reduction in open arm entries together with an increased anxiety index was detected in CRS-exposed animals; open field parameters did not change significantly. A decreased density of total dendritic spines, in parallel with higher and lower numbers of thin and stubby spines, respectively, was observed in CeA neurons. Results suggest that CRS-induced anxiety-like behavior might be accounted for by a reduction in synaptic connectivity of the CeA. This effect, which is long lasting, could mediate the persisting anxiogenic effects of chronic stress after exposure to it has ended.

Comparing the effects of crocin at different doses on excitability and long-term potentiation in the CA1 area, as well as the electroencephalogram responses of rats under chronic stress.

Stress adversely affects the cellular and electrophysiological mechanisms of memory; however, crocin has beneficial effects on brain functions. Nonetheless, the electrophysiological effects of using this active saffron component at different doses are not yet studied in rats under chronic restraint stress. Therefore, this study compared the impact of crocin at different doses on the excitability and long-term potentiation(LTP) in the CA1 area of rats, as well as their electroencephalogram(EEG) responses, hippocampal and frontal cortical glucose levels under chronic restraint stress (an emotional stress model).Forty rats were allocated into five groups of control, sham, restraint stress (6h/day/21days), and two stress groups receiving intraperitoneal injections of crocin (30, 60mg/kg/day). Besides measuring the slope and amplitude of field excitatory postsynaptic potentials(fEPSPs) in the input-output and LTP curves, the EEG waves and hippocampal and frontal cortical glucose levels were assessed in all groups.Chronic restraint stress significantly decreased the fEPSP slope and amplitude in the input-output curves and after LTP induction. Both doses of crocin (60and particularly 30mg/kg) significantly improved fEPSP slope and amplitude in the stressed groups. Also, stress and crocin only at a dose of 30mg/kg altered the EEG waves. Hippocampal and frontal cortical glucose levels displayed no significant differences in the experimental groups.Crocin at doses of 60mg/kg/day and particularly 30mg/kg/day reversed the harmful effects of chronic restraint stress on LTP as a cellular memory-related mechanism. However, only the lower dose of crocin affected the electrical brain activity in EEG.

Role and Mechanism of Chronic Restraint Stress in Regulating Energy Metabolism and Reproductive Function Through Hypothalamic Kisspeptin Neurons

Objectives: The purpose of this study was to investigate whether stress affected energy metabolism and reproductive function through the glucocorticoid receptor (GR) on Kisspeptin neurons in the hypothalamus. Methods: 1. The first part of this study focused on the effects of chronic restraint stress on energy metabolism and reproductive function in mice. 2. The second part of this study focused on the effects of chronic restraint stress on the expression of serum cortisol and prolactin and the expression of GR and Kiss1 genes in the hypothalamus.3. Based on the above research, we constructed Kisspeptin specific glucocorticoid receptor knock out (KGRKO) mice. The mice were subjected to restraint stress intervention, the body weight of the mice was monitored every day, and the vaginal smear was performed on the female mice to observe the estrous cycle. After 28 days of restraint stress, serum was collected to detect serum sex hormone levels, including LH, FSH and estrogen levels in female mice and testosterone level in male mice by ELISA. Results: 1.The body weight and energy intake of the restraint stress group were lower than those of the control. 2.After restraint stress, the female mice showed irregular estrous cycle. LH and FSH levels in the stress group were significantly decreased compared with the control group.3. After restraint stress, the levels of serum cortisol and prolactin in male and female mice were significantly higher than the control group, and the hypothalamus Kiss1 gene mRNA expression and Kisspeptin protein expression were significantly decreased.4. In female mice, compared with GRflox/flox/Kiss1Cre-control mice, the nadir serum cortisol increased significantly in the morning in GRflox/flox/Kiss1Cre+ KGRKO mice, however, there was no significant difference in the serum peak cortisol in the afternoon. Compared with the control group, the restraint stress group and the KGRKO + restraint stress group had a significant weight loss compared with the KGRKO group. Compared with the restraint stress group, the KGRKO+restraint stress group had a reduced weight loss, suggesting that restraint stress might partially affect the energy metabolism through GR on Kisspeptin neurons. Conclusions: Chronic restraint stress induced weight loss in mice and reversed body weight gain induced by high-fat diet. Chronic restraint stress played a negative role in regulating reproductive function. The effects of chronic restraint stress on energy metabolism and reproduction were partially mediated by GR on Kisspeptin neurons in the hypothalamus. This study provided a central mechanism for chronic restraint stress in affecting energy metabolism and reproductive function, and was of great significance in revealing the relationship between the HPA axis with energy metabolism and reproduction.

Chronic restraint stress impairs cognition via modulating HDAC2 expression.

BackgroundTo investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice.MethodsIn the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress.ResultsDecreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions.ConclusionThis work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.

Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis

Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis.

Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling.

Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C γ (PLCγ) pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.

Chronic Restraint Stress Affects Network Oscillations in the Anterior Cingulate Cortex in Mice

The anterior cingulate cortex (ACC) is vulnerable to stress. Its dysfunction is observed in psychiatric disorders manifested as alterations in network oscillations. Mechanisms linking stress load to disturbed emotional–cognitive behaviors are of essential importance to further elucidate therapeutic strategies for psychiatric diseases. Here, we analyzed the effects of chronic restraint stress (CRS) load in juvenile mice on kainic acid (KA)-induced network oscillations in ACC slice preparations and on the forced swim test (FST). The immobility time (IT) was shortened at the beginning of the FST in CRS mice. Power spectral density (PSD) obtained from KA-induced oscillations in field potentials in the superficial layers of the ACC were altered in slices from the CRS mice. The PSD was decreased in CRS mice at the alpha (8–12 Hz), beta (13–30 Hz), low gamma (30–50 Hz), and high gamma (50–80 Hz) components. Noradrenaline increased the PSD of the theta (3–8 Hz) components in both the control and CRS groups, and also in alpha components only in the CRS group. Dopamine did not modulate the PSD of any frequency components in the control mice, whereas it enhanced the PSD of theta and alpha components in CRS mice. It was suggested that chronic stress load affects the dynamics of the network oscillations in the ACC with enhanced cathecolaminergic modulation.

Changes of Hippocampal Noradrenergic Capacity in Stress Condition

This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-β-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition.

Chronic restraint stress induces esophageal fibrosis with enhanced oxidative stress in a murine model

Although the underlying mechanism of stress remains unknown, it has been associated with the pathophysiology of gastroesophageal reflux diseases, the development of which appear to be accelerated by oxidative stress and fibrosis. The aim of the current study was to investigate the effect of chronic restraint stress on esophageal oxidative stress and fibrosis, as well as the impact of oxidative stress in a murine model whereby 8-week old C57BL/6J male mice were subjected to intermittent chronic restraint stress for a two-week period. The current study demonstrated that chronic restraint stress significantly reduced the body weight of mice compared with the control group. Although chronic restraint stress did not significantly alter the levels of triglycerides or cholesterol, free fatty acid concentration was significantly increased compared with the control group. Furthermore, chronic restraint stress significantly upregulated the expression levels of several fibrotic biomarkers including collagen type I, transforming growth factor β-1, α-smooth muscle actin and SMAD-3 compared with the control group. In addition, the expression levels of the reactive oxygen species (ROS) NADPH oxidase-4 and malondialdehyde were significantly increased, while the expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 were significantly decreased in esophageal tissue from mice in the chronic restraint stress group compared with the control group. In conclusion, chronic restraint stress may induce esophageal fibrosis by accumulating ROS and increasing fibrotic gene expression in a murine model.

Neuroinflammation caused by mental stress: the effect of chronic restraint stress and acute repeated social defeat stress in mice

ABSTRACTObjectives: Cerebrovascular disease (CVD) is the leading cause of permanent disability worldwide. Inflammation has been reported to play an important role in the progression of CVD. Neuropsychiatric disorders such as depression are associated with increased incidence of CVD epidemiologically, although the mechanisms underlying this association are not clear. In this study, we assessed the effect of the acute repeated social defeat stress (RSDS) and chronic restraint stress (CRS) on neuroinflammation in mice.Methods: A total of 40 6-week-old male C57BL/6J mice were divided into RSDS, CRS, and corresponding control groups. In the RSDS group, male C57BL/6J mice were repeatedly subjected to bouts of social defeat by a larger CD-1 mouse for 10 min daily for 10 consecutive days. In the CRS group, the mice were exposed to restraint stress for 6 h per day for 28 consecutive days. Depressive behavior was evaluated by conducting sucrose preference test over 24 h. Peripheral blood serum and brain tissues were collected for measurement of corticosterone (CORT), epinephrine (EPI), and inflammatory factors (TNF-α and IL-6) using ELISA or real-time PCR 24 h after the sucrose preference test.Results: Both RSDS and CRS decreased the sucrose preference ratio. The acute stress increased serum CORT and EPI, while the chronic stress did not significantly influence them. Both stress models induced an inflammatory response in peripheral serum and the brain.Conclusions: RSDS and CRS are two effective models of depressive behavior, and both models cause neuroinflammation, which may be responsible for the increased risk of CVD seen in patients with depression.

Chronic stress produces enduring sex- and region-specific alterations in novel stress-induced c-Fos expression

Prolonged or repeated exposure to stress increases risk for a variety of psychological disorders, many of which are marked by dysfunction of corticolimbic brain regions. Notably, women are more likely than men to be diagnosed with these disorders, especially when onset of symptoms follows stressful life events. Using rodent models, investigators have recently begun to elucidate sex-specific changes in the brain and behavior that occur immediately following chronic stress. However, little is known regarding the lasting sequelae of chronic stress, as well as how potential changes may impact responsivity to future stressors. We recently demonstrated that male and female rats show different patterns of dendritic reorganization in medial prefrontal cortex in the days following chronic stress. Here, we examined the immediate and lasting effects of chronic restraint stress (CRS; 3 h/day, 10 days) on neuronal activation, across several corticolimbic brain regions, induced by novel acute stress exposure. Chronically stressed male and female rats were exposed to acute elevated platform stress (EPS) either 1 (CRS-EPS) or 7 (CRS-Rest-EPS) days after CRS. Compared to rats exposed to EPS only, significant reductions in acute stress-induced c-Fos expression were observed in the medial prefrontal cortex, hippocampus, and paraventricular nucleus of the hypothalamus (PVN) in CRS-EPS male rats, some of which persisted to 7 days post-stress. In contrast, we found little modulation of novel stress-induced c-Fos expression in CRS-EPS female rats. However, CRS-Rest-EPS female rats exhibited a significant enhancement of acute stress-induced neuronal activity in the PVN. Together, these data show that prior chronic stress produces sex- and region-specific alterations in novel stress-induced neuronal activation, which are dependent on the presence or absence of a rest period following chronic stress. These findings suggest that the post-stress rest period may give rise to sex-specific neuroadaptations to stress, which may underlie sex differences in stress susceptibility versus resilience.