Stress Response In Mice Research Articles

Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes

BackgroundLow serum osteocalcin is a risk factor for type 2 diabetes mellitus (T2DM), and osteocalcin release from bone is associated with an acute stress response in mice. Both diabetes and stress are associated with depression. Here, we assess relationships between serum osteocalcin, depression and subjective stress in people with T2DM. MethodsParticipants with T2DM (HbA1c above 6.4 %, impaired fasting glucose or impaired glucose tolerance) were assessed for a major depressive episode using the research version of the Structured Clinical Interview for DSM-5 depression criteria (SCID-5RV). Subjective stress over the past month was assessed using the Perceived Stress Scale (PSS). Serum carboxylated (cOCN) and fully decarboxylated (dcOCN) osteocalcin were assayed from fasting morning blood by commercial enzyme-linked immunosorbent assay. ResultsAmong 95 participants (mean age 62.4 ± 9.9, 51 % women), 22 % were experiencing a depressive episode (9 men, 12 women). The presence of a depressive episode was not associated with dcOCN or cOCN concentrations; however, higher concentrations of cOCN were associated with higher PSS scores in participants with depression (r = 0.585, p = 0.005). In an analysis of covariance model controlling for age, sex, body mass index, glycemic control (glycosylated hemoglobin), insulin resistance (homeostatic model), depression, and antidepressant use, cOCN was associated with PSS scores (F=10.302, p = 0.002), and this relationship was stronger in those with depression (depression × cOCN interaction F=4.978, p = 0.028). Although associations between dcOCN concentrations and PSS scores did not reach significance, the same trend seen with cOCN concentrations was observed in participants with depression for dcOCN (r=0.365, p=0.10), and for a depression × dcOCN interaction associated with PSS scores in the whole group (F=2.165, p = 0.15). ConclusionsOsteocalcin is a neuroendocrine marker associated with perceived chronic stress among people with T2DM experiencing a depressive episode.

Participation of Hsp70 and Hsp90α Heat Shock Proteins in Stress Response in the Course of Type 1 Diabetes Mellitus.

The role of two heat shock proteins, Hsp70 and Hsp90α, on stress response in mice with severe diabetes mellitus induced by a high dose of alloxan (500 mg/kg body weight), as well as in RIN-m5F β cells cultured in the presence of cytokines (IL-1 and TNF-α) was studied. Our results showed that severe type 1 diabetes mellitus (T1D) caused a higher expression of Hsp90α, but not Hsp70. Moreover, injections of the peroxiredoxin 6 antioxidant enzyme (PRDX6) did not affect the expression of these chaperones. Conversely, pro-inflammatory cytokines added to β-cells caused a significant increase in the expression of Hsp90α and, substantially, Hsp70. Moreover, cells cultivated in the presence of PRDX6 were more susceptible to the cytokine effect. Thus, in the course of severe alloxan-induced T1D, no protective role of the heat shock proteins, was revealed, and their expression level was not increased by PRDX6. At the same time the protective potential of these proteins was shown in vitro with the use of RIN-m5F β cells. Thus, the system of heat shock proteins was unable to prevent the devastating effects of severe T1D accompanied by high animal mortality.

6-Gingerol abates benzo[a]pyrene-induced colonic injury via suppression of oxido-inflammatory stress responses in BALB/c mice

Exposure to benzo[a]pyrene (BaP), the most toxic polycyclic aromatic hydrocarbon and a procarcinogen, is a global health concern which necessitates preventive measures. [6]-Gingerol (6-G), the most pharmacologically active constituent of ginger has been reported to promote gut health in various experimental settings. This study investigated the role of 6-G in BaP-induced colonic oxidative and inflammatory stress responses in mice. Experimental mice were randomly assigned into five groups of eight mice each and were orally gavage with BaP (125 mg/kg) singly or in combination with 6-G at 50 and 100 mg/kg for 14 consecutive days. Following sacrifice, the colonic activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), myeloperoxidase (MPO) as well as levels of glutathione (GSH), nitrites and lipid peroxidation (LPO) were assessed spectrophotometrically. Moreover, colonic concentration of epoxide hydrolase (EPXH), tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were assessed using ELISA. Administration of 6-G augmented BaP detoxification and colonic antioxidant status by increasing the EPXH, GST, SOD and CAT activities, GSH level with concomitant decrease in MDA level when compared with BaP alone group. In addition, 6-G suppressed BaP-induced colonic inflammation by decreasing MPO activity as well as nitrites, TNF-α, IL-1β, COX-2 and iNOS levels when compared with BaP alone group. In conclusion, 6-G protected against a decrease in colonic epoxide detoxifying enzymes and antioxidant defense mechanisms caused by BaP.

Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice.

Glycosylation is a post-translational protein modification in eukaryotes and plays an important role in controlling several diseases. N-glycan structure is emerging as a new paradigm for biomarker discovery of neuropsychiatric disorders. However, the relationship between N-glycosylation pattern and depression is not well elucidated to date. This study aimed to explore whether serum N-glycan structures are altered in depressive-like behavior using a stress based mouse model. We used two groups of BALB/c mice; (i) treated group exposed to chronic unpredictable mild stress (CUMS) as a model of depression, and (ii) control group. Behavioral tests in mice (e.g., sucrose preference test, forced swimming test, and fear conditioning test) were used to evaluate the threshold level to which mice displayed a depressive-like phenotype. Serum N-glycans were analyzed carefully using glycoblotting followed by Matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) to exhibit N-glycan expression levels and to illustrate the changes in the N-glycome profile. N-glycan expression levels were commonly altered in the depressive-like model and correlated well with the behavioral data. Our results indicated that sialylated N-glycan was identified as a biomarker associated with depressive symptoms, which may have utility as a candidate biomarker for the clinical diagnosis and monitoring of depression.

Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression.

Flavonoid-Rich Fraction of Ocimum gratissimum Attenuates Lipopolysaccharide-Induced Sickness Behavior, Inflammatory and Oxidative Stress in Mice.

Ocimum gratissimum L. leaves has been traditionally used for management of febrile illnesses and symptoms typified of sickness behavior. In this work we investigated the modulatory effect of flavonoid-rich fraction of O. gratissimum leaves (EAFOg) on sickness behavior, inflammatory and oxidative stress responses in LPS-challenged mice. O. gratissimum leaf was first extracted with n-hexane, chloroform and methanol, and EAFOg was obtained by ethylacetate partitioning of a sequentially resultant methanol extract. The effect of EAFOg (25-100 mg/kg) on acute LPS-induced neurobehavioral impairment in an open field test (OFT) and depressive-like behavior in forced swimming test (FST) was investigated. Serum nitrite and TNF-α, as well as myeloperoxidase (MPO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in liver and brain tissues. EAFOg prevented the reduction in locomotor and rearing activity in OFT and the increase in immobility time in FST. The fraction significantly attenuated the elevation of serum TNF- α and nitrite levels. EAFOg reversed LPS-induced increase in MDA, MPO, and nitrite levels and attenuated GSH depletion in liver and brain tissues of mice. Flavonoid-rich fraction of O. gratissimum leaf demonstrated significant modulation of LPS-induced sickness behavior, inflammatory and oxidative stress response in mice. This suggests an important therapeutic strategy in slowing down LPS-mediated hepatic and neuronal disease processes.

Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors.

Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here we examined a possible role for the DNA dioxygenase, ten-eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region. We show decreased Tet1 expression in NAc in stress-susceptible mice only. Surprisingly, selective knockout of Tet1 in NAc neurons of adult mice produced antidepressant-like effects in several behavioral assays. To identify Tet1 targets that mediate these actions, we performed RNAseq on NAc after conditional deletion of Tet1 and found that immune-related genes are the most highly dysregulated. Moreover, many of these genes are also upregulated in the NAc of resilient mice after chronic social defeat stress. These findings reveal a novel role for TET1, an enzyme important for DNA hydroxymethylation, in the brain's reward circuitry in modulating stress responses in mice. We also identify a subset of genes that are regulated by TET1 in this circuitry. These findings provide new insight into the pathophysiology of depression, which can aid in future antidepressant drug discovery efforts.

Stress-Dependent Changes in the CacyBP/SIP Interacting Protein S100A6 in the Mouse Brain.

The CacyBP/SIP target S100A6 is widely present in the nervous system, and its up-regulation is associated with certain neurodegenerative diseases. Here, we examined the involvement of S100A6 protein in stress responses in mice. Using Western blotting, we observed a marked change in brainstem structures, whereby stressed mice showed approximately one-third the protein level produced in the control group. A decreased level of S100A6 protein in stressed animals was also detected in the olfactory bulb and the cerebellum and stress-related structures such as the hippocampus and the hypothalamus. Additionally, using immunohistochemistry, high levels of S100A6 expression were observed in astrocytes localized in the border zones of all brain ventricles, tanycytes of the ventro-lateral walls of the hypothalamus, including the arcuate nucleus (ARH) and low levels of this protein were in neurons of the olfactory bulb, the hippocampus, the thalamus, the cerebral cortex, the brainstem and the cerebellum. Although S100A6-expressing cells in all these brain structures did not change their phenotype in response to stress, the intensity of immunofluorescent labeling in all studied structures was lower in stressed mice than in control animals. For example, in the ARH, where extremely strong immunostaining was observed, the number of immunolabeled fibers was decreased by approximately half in the stressed group compared with the controls. Although these results are descriptive and do not give clue about functional role of S100A6 in stress, they indicate that the level of S100A6 decreases in several brain structures in response to chronic mild stress, suggesting that this protein may modify stress responses.

Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a classical target for antidiabetic therapies with thiazolidinedione compounds. PPARγ agonists such as rosiglitazone and pioglitazone are in clinical use for the treatment of insulin resistance. PPARγ has recently attracted attention for its involvement in the regulation of CNS immune response and functions. Here, we demonstrate that neuronal PPARγ activation prevented the negative emotional effects of stress and exerted anxiolytic actions without influencing hypothalamic-pituitary-adrenal axis function. Conversely, pharmacological blockade or genetic deletion of PPARγ enhanced anxiogenic responses and increased vulnerability to stress. These effects appear to be controlled by PPARγ neuronal-mediated mechanisms in the amygdala.

Effect of perioperative infection factor on apoptosis in hippocampal neurons after surgery in mice

Objective To evaluate the effect of the perioperative infection factor on apoptosis in hippocampal neurons after surgery in mice. Methods Ninety-six healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups (n=24 each) using a random number table: control group (group C), surgery group (group S), infection group (group I) and infection + surgery group (group I+ S). Open reduction and internal fixation was performed after tibial fracture was induced in S and I+ S groups.In I and I+ S groups, lipopolysaccharide 100 μg/kg was injected intraperitoneally at 1 day and 2 h before surgery and 1, 2 and 3 days after surgery once a day for 5 consecutive days.At 1 and 3 days after surgery, 12 mice in each group were selected to perform the contextual fear conditioning test, and the rate of time spent freezing was recorded to evaluate the cognitive function.At 1 day after surgery, venous blood samples were collected for determination of concentrations of adrenocorticotrophin in serum and corticosterone in plasma.After the contextual fear conditioning test, the mice were sacrificed, and the hippocampi were removed to detect the neuronal apoptosis and expression of activated caspase-3, activated poly(ADP-ribose) polymerase-1, Bax and Bcl-2.The apoptosis index and ratio of Bax to Bcl-2 were calculated. Results Compared with group C, the rate of time spent freezing was significantly decreased (P 0.05). Compared with group S, the rate of time spent freezing was significantly decreased, the concentrations of adrenocorticotrophin in plasma and corticosterone in serum were increased, the apoptosis index and Bax/Bcl-2 ratio were increased, and the expression of activated caspase-3 and poly(ADP-ribose) polymerase-1 was up-regulated in group I+ S(P<0.01). Conclusion The mechanism by which perioperative infection factor aggravates postoperative cognitive dysfunction is related to induction of apoptosis in hippocampal neurons through enhancing stress responses in mice. Key words: Bacterial infections; Intraoperative period; Postoperative complications; Cognition disorders; Apoptosis; Hippocampus; Neurons

The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility is also important. Light intensity, isoflurane, and CO2 flow rate were studied for their impact on the stress response of mice during CO2 euthanasia. Behavior was observed and scored during euthanasia and serum corticosterone was measured immediately after death. Unsurprisingly, animals euthanized with a high-flow rate of CO2 became unconscious in the least amount of time, while animals euthanized with a low-flow rate required the most time to reach unconsciousness. There was a significant increase in anxious behaviors in animals in the isoflurane group (F1,12 = 6.67, P = 0.024), the high-flow rate CO2 group (F1,12 = 10.24, P = 0.007), and bright chamber group (F1,12 = 7.27, P = 0.019). Serum corticosterone was highest in the isoflurane group (124.72 ± 83.98 ng/ml), however there was no significant difference in corticosterone levels observed for the other study variables of light and flow-rate. A darkened chamber and low CO2 flow rates help to decrease stress experienced during CO2 euthanasia, while the use of isoflurane was observed to increase the stress response during euthanasia.

CD44 Deficiency Is Associated with Increased Susceptibility to Stress-Induced Anxiety-like Behavior in Mice.

CD44 is a cell surface adhesion molecule and its principal ligand is hyaluronic acid (HA), a key component of the brain's extracellular matrix. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in genome wide association study as a possible risk gene in suicidal behavior. In order to define the pathobiological mechanisms by which CD44 may affect behavior, we investigated the role of CD44 using male CD44 knockout (CD44KO) and wild-type mice that underwent chronic mild stress (CMS). Behavior was characterized using the sucrose preference and forced swim tests, open field, novel object recognition, social preference, and the elevated plus maze tests. Gene expression in hippocampus was evaluated using quantitative real-time PCR. Brain monoamines and their metabolites were assessed by high-performance liquid chromatography and serum HA and IL-1β levels were measured using ELISA and electrochemiluminescence assays. CD44KO mice were more susceptible to stress-induced anxiety-like behavior and displayed increased anhedonia and despair than the wild-type controls. The behavioral phenotype of stressed CD44KO mice was associated with reduced cortical serotonergic and striatal dopaminergic turnover. The hippocampal expression of the receptor for HA-mediated motility (RHAMM) was reduced in the non- stressed CD44KO mice compared with WT mice, in a value similar to that observed in WT mice following exposure to stress. Taken together, our experiments suggest that CD44 plays a key role in stress response in mice.

Abstract # 1771 Experimental procedures performed sequentially exert a stress that activates caspase-1 and impairs memory in mice

Various forms of psychological and physical stress, such as restraint and chronic mild stress, have been shown to activate the neuroimmune system and lead to cognitive impairment and depressive-like behaviors. Additionally, it has been shown that minor environmental changes, and even changes in gender, can induce stress responses in mice. Many of these models show increases in the pro-inflammatory cytokine IL-1 β . IL-1 β is produced in an inactive form and requires activation by caspase-1, which is activated by the sensing of a danger signal by the inflammasome complex. However, the danger signals responsible for these changes remains unknown. Here, we show that a novel stressor paradigm of common experimental procedures (weighing, scruffing, and needle pricks) performed sequentially can activate caspase-1 and impair memory which is dependent on adenosine signaling. 6 hr of stress increases caspase-1 activity 2–3 fold in the amygdala, hippocampus, and prefrontal cortex and impairs novel object recognition. However, 3 hr of stress was unable to change object recognition memory. Additionally, stress-induced memory impairment and caspase-1 activation can be blocked by IP administration of the pan-adenosine receptor antagonist caffeine. Finally, we show that stress-induced memory impairment can also be blocked by genetic knockout of the adenosine A2 receptor (A2AR). Taken together, these data show that common experimental techniques can exert a stress response in mice that is dependent on adenosine-induced caspase-1 activation.

Genetic regulation analysis reveals involvement of tumor necrosis factor and alpha-induced protein 3 in stress response in mice

In order to study whether Tnfaip3 is related to stress response and further to find it's genetic regulation, we use C57BL/6J (B6) and DBA/2 (D2) mice to built the model of chronic unpredictable mild stress. RT-PCR, Western blotting and immunohistochemistry were used for studying the expression variation of Tnfaip3 in hippocampus tissue of B6 and D2 mice after being stressed. We found that the expression of Tnfaip3 was more remarkably increased in chronic unpredictable stress models than that in untreated mice (P<0.05). It is indicated that Tnfaip3 might take part in the process of stress response. The expression of Tnfaip3 is regulated by a cis-acting quantitative trait locus (cis-eQTL). We identified 5 genes are controlled by Tnfaip3 and the expression of 64 genes highly associated with Tnfaip3, 9 of those have formerly been participate in stress related pathways. In order to estimate the relationship between Tnfaip3 and its downstream genes or network members, we transfected SH-SY5Y cells with Tnfaip3 siRNA leading to down-regulation of Tnfaip3 mRNA. We confirmed a significant influence of Tnfaip3 depletion on the expression of Tsc22d3, Pex7, Rap2a, Slc2a3, and Gap43. These validated downstream genes and members of Tnfaip3 gene network provide us new insight into the biological mechanisms of Tnfaip3 in chronic unpredictable stress.

NPY-Y1 coexpressed with NPY-Y5 receptors modulate anxiety but not mild social stress response in mice.

The Y1 and Y5 receptors for neuropeptide Y have overlapping functions in regulating anxiety. We previously demonstrated that conditional removal of the Y1 receptor in the Y5 receptor expressing neurons in juvenile Npy1r(Y5R-/-) mice leads to higher anxiety but no changes in hypothalamus-pituitary-adrenocortical axis activity, under basal conditions or after acute restraint stress. In the present study, we used the same conditional system to analyze the specific contribution of limbic neurons coexpressing Y1 and Y5 receptors on the emotional and neuroendocrine responses to social chronic stress, using different housing conditions (isolation vs. group-housing) as a model. We demonstrated that control Npy1r(2lox) male mice housed in groups show increased anxiety and hypothalamus-pituitary-adrenocortical axis activity compared with Npy1r(2lox) mice isolated for six weeks immediately after weaning. Conversely, Npy1r(Y5R-/-) conditional mutants display an anxious-like behavior but no changes in hypothalamus-pituitary-adrenocortical axis activity as compared with their control littermates, independently of housing conditions. These results suggest that group housing constitutes a mild social stress for our B6129S mouse strain and they confirm that the conditional inactivation of Y1 receptors specifically in Y5 receptor containing neurons increases stress-related anxiety without affecting endocrine stress responses.

Mitochondrial functions modulate the stress response in mice

The aim of this study was to test whether glucocorticoid hormones can directly affect olfactory function. Following detection of the glucocorticoid receptor (GR) in the OM, we hypothesised that: (1) GR action could be pharmacologically regulated in vitro; (2) acute in vivo (2mg/kg ip, 6h) injection of synthetic glucocorticoid (dexamethasone) would affect OM gene expression and electrophysiological properties; (3) dexamethasonewould alter rat behaviour in response to olfactory stimulation In contrast with published data, GR was not expressed in OSN but in the gliallike Olfactory Ensheathing Cells (OEC). In OEC primary cultures, expression of a GR activation marker gene (SGK1) was increased by dexamethasone, but repressed with the antagonist RU486. In vivo, SGK1 and other GR-regulated transcripts were affected by dexamethasone. This was accompanied by up to 30% reduction in ElectroOlfactoGram signal amplitude in response to odorants. Dexamethasone did not affect rat behaviour in an open field, but their reactivity was increased in an olfactory-based habituationdishabituation task. The first step of olfactory detection is sensitive to glucocorticoid hormones; we are further investigating the biological significance of this phenomenon.

Short-Term &lt;I&gt;in Situ Action&lt;/I&gt; of Melatonin on Ion Transport in Mice Kept at Restraint Stress

Melatonin, a pleiotropic hormone, is involved in many physiological functions including combating oxidative stress. However, its role in ion transport during stress response is not yet understood. The dose-dependent effect of in situ melatonin was examined in Swiss albino mice. Perfusion of melatonin at 10 -7 M for 20 minutes produced a significant decrease in Na + , K + -ATPase activity in the kidney, liver, stomach and intestinal tissues. A dose-responsive decrease in cytosolic and mitochondrial H + ATPase activity was found in these tissues after melatonin perfusion. Likewise, the cytosolic and mitochondrial Ca 2+ ATPase activities decreased in the kidney, liver, stomach and intestine. The mitochondrial Mg 2+ ATPase activity decreased in the tested tissues in a dose-responsive manner. Subjecting mice to restraint stress for seven days increased the Na + , K + -ATPase, H + ATPase, Ca 2+ ATPase and Mg 2+ ATPase activities to significant levels in kidney, liver, stomach and intestinal tissues. On the contrary, in-situ perfusion of melatonin to stressed mice at 10 -9 M caused decrease in the stress-induced hyperactivity of these transmembrane ion transporters. These results provide evidence for a role of melatonin in ion transporter activity and point to a protective role of melatonin in ion transport during stress response in mice.

The expression of interleukin-6 and its receptor in various brain regions and their roles in exploratory behavior and stress responses

We examined the involvement of interleukin-6 (IL-6) and its receptor IL-6Rα on behavior and stress responses in mice. In the open field, both wild-type (WT) and IL-6 deficient mice displayed similar levels of locomotor activity; however, IL-6 deficient mice spent more time in the central part of the arena compared to control WT mice. After behavioral testing, mice were subjected to stress and then sacrificed. The levels of IL-6 and its receptor in their brains were determined. Immunohistochemical labeling of brain sections for IL-6 showed a high level of expression in the subventricular zone of the lateral ventricles and in the border zone of the third and fourth ventricles. Interestingly, 95% of the IL-6-expressing cells had an astrocytic phenotype, and the remaining 5% were microglial cells. A low level of IL-6 expression was observed in the olfactory bulb, hypothalamus, hippocampus, cerebral cortex, cerebellum, midbrain and several brainstem structures. The vast majority of IL-6-expressing cells in these structures had a neuronal phenotype. Stress increased the number of IL-6-immunoreactive astrocytes and microglial cells. The levels of the IL-6Rα receptor were increased in the hypothalamus of stressed mice. Therefore, in this study, we describe for the first time the distribution of IL-6 in various types of brain cells and in previously unreported regions, such as the subventricular zone of the lateral ventricle. Moreover, we provide data on regional distribution and expression within specific cell phenotypes. This highly differential expression of IL-6 indicates its specific roles in the regulation of neuronal and astrocytic functions, in addition to the roles of IL-6 and its receptor IL-6Rα in stress responses.

Exposure to 50 Hz electric fields reduces stress-induced glucocorticoid levels in BALB/c mice in a kV/m- and duration-dependent manner.

Electric fields (EFs) can reduce elevated levels of stress-related hormones in some organisms. In this study, endocrine effects of exposure to a 50 Hz EF were investigated in male BALB/c mice. Specifically, plasma glucocorticoid (GC) levels were examined because GC is known to mediate the stress response in mice, including changes induced by immobilization. Mice were exposed to 50 Hz EFs (at 2.5-200 kV/m) for 60 min. They were immobilized for the latter half (30 min). At the end of exposure period, blood samples were collected and GC levels estimated by spectrofluorometry. GC levels were not influenced by EFs in absence of immobilization, but they were significantly higher in immobilized mice than in non-immobilized mice (P < 0.01). Elevated GC levels induced by immobilization were significantly reduced by exposure to an EF at 10 kV/m (P < 0.05), and the effect of EFs at 0-10 kV/m on GC levels increased in a kV/m-dependent manner (P < 0.05). In contrast, following treatment with EFs at 50 and 200 kV/m, GC levels were higher than those observed at 10 kV/m. To assess the effect of EF treatment duration, mice were also exposed to 50 Hz EFs (10 kV/m) for 6, 20, or 60 min. Immobilization-induced increase in GC levels was significantly suppressed by EF exposure for 20 and 60 min. Therefore, our results demonstrate that extremely low-frequency EFs alter stress response of mice in a kV/m- and duration-dependent manner.

Effects of Methyl Jasmonate on Acute Stress Responses in Mice Subjected to Forced Swim and Anoxic Tests.

Methyl jasmonate (MJ) is an anti-stress hormone released by plants in response to external stressors and aids adaptation to stress. In this study, we evaluated the anti-stress activity of MJ using the forced swim endurance test (FSET) and anoxic tolerance test in mice. Male Swiss mice were given MJ (25–100 mg/kg, i.p) 30 min before the FSET and anoxic test were carried out. The first occurrence of immobility, duration of immobility, time spent in active swimming, and latency to exhaustion were assessed in the FSET. The onset to anoxic convulsion was measured in the anoxic tolerance test. MJ significantly (p < 0.05) delayed the first occurrence of immobility and shortened the period of immobility, which indicates anti-stress property. MJ also increased the time spent in active swimming and prolonged the latency to exhaustion, which further suggests anti-stress activity. In addition, it also exhibited anti-stress property as evidenced by prolonged latency to first appearance of anoxic convulsions. The results of this study suggest that MJ demonstrated anti-stress activity and may be useful as an energizer in times of body weakness or exhaustion. Although more studies are necessary before concluding on how MJ exerts its anti-stress activity, the present data suggest an action similar to adaptogens in boosting energy and resilience in the face of stress.