Humans ; Occupational Diseases ; diagnosis ; Saliva ; chemistry ; metabolism ; Stress, Psychological ; diagnosis

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cognitive Dysfunction/complications* ; DNA Methylation ; Homocysteine/metabolism* ; Hyperhomocysteinemia/metabolism* ; Rats ; Stress, Psychological/physiopathology*

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.
Rats ; Mice ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Ghrelin/metabolism* ; Antidepressive Agents/therapeutic use* ; Hippocampus ; Stress, Psychological ; Mammals/metabolism*

AIMTo elucidate the mechanism of depression induced by chronic unpredictable mild stress (CUMS), the effects of CUMS on serotonin (5-HT), tryptophan, stress hormones and behaviour were investigated in rats.

METHODSDepression was induced by for 8 weeks CUMS and confirmed by behavioral tests, the brain and plasma levels of monoamine neurotransmitters were analyzed by HPLC-ECD techniques, the content of plasma corticosterone was evaluated by I125 cortisol radioactivity immunoassay and the serum tryptophan content was measured by HTTACHI L-8800 amino acid analyzer.

RESULTS(1) Rats exposed to a series of mild, unpredictable stressors for 8 weeks displayed the decreased body weight, reduced scores of open-field test and preference of sucrose solution (P < 0.05). (2) Plasma and brain 5-HT contents in rats after exposure to CUMS 8 weeks decreased significantly (P < 0.05). While serum tryptophan content increased at the same time (P < 0.05). (3) Plasma norepinephrine and epinephrine in rats were increased after CUMS 8 weeks, but there was no difference between control and CUMS group in plasma corticosterone.

CONCLUSIONThe behavioral changes induced by CUMS for 8 weeks are similar to the features of human depression, which may be related to the disturbances of tryptophan metabolism induced by increased norepinephrine and epinephrine in CUMS rat.

Animals ; Depression ; metabolism ; Epinephrine ; metabolism ; Hippocampus ; metabolism ; Male ; Neurosecretory Systems ; metabolism ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Stress, Psychological ; metabolism

PURPOSE: Purpose of this study was to examine the effects of the Mindfulness Meditation program on perceived stress, ways of coping, salivary cortisol level, and psychological stress response in patients with breast cancer. METHODS: This was a quasi-experimental study with a non-equivalent control group pre-post test design. Participants in this study were 50 patients who had completed breast cancer treatment (experimental group, 25, control group, 25). The experimental group received the Mindfulness Meditation program for 3 hours/session/ week for 8 weeks. Data were analyzed using chi2-test and t-test for subject homogeneity verification, and ANCOVA to examine the hypotheses. RESULTS: The experimental group had significantly lower scores for perceived stress, emotional focused coping, salivary cortisol level, and psychological stress response compared to the control group. However, no significant differences were found between two groups for the scores on problem focused stress coping. CONCLUSION: According to the results, the Mindfulness Meditation program was useful for decreasing perceived stress, emotional focused coping, salivary cortisol level, and psychological stress response. Therefore, this program is an effective nursing intervention to decrease stress in patients with breast cancer.
Adaptation, Psychological ; Adult ; Breast Neoplasms/metabolism/pathology/*psychology ; Emotions ; Female ; Humans ; Hydrocortisone/analysis ; Middle Aged ; Perception ; *Program Evaluation ; Questionnaires ; Salivary Glands/metabolism ; Stress, Psychological

OBJECTIVETo study the feasibility of monoamine neurotransmitters, serum glucose, serum glycerinate and cholesterol as objective indices for evaluating occupational stress.

METHODSJob stressors, modifiers, job strains in 844 people with four kinds of occupation were investigated, and the concentration of monoamine neurotransmitters, glucose, glycerinate and cholesterol in blood were detected at the same time. The methods of multiple stepwise regression and covariance analysis were used to analyze the data.

RESULTSThere was close relationship between monoamine neurotransmitters and job stressors, the forecast of the equation of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) was 0.7238, 0.5703, 0.4438 respectively, the critical values of them were 804.00, 226.00 and 275.00 ng/ml respectively. There was a little contribution of job stressors to the equation of glucose, glycerinate and cholesterol, the critical values were 6.40, 2.51 and 5.92 mmol/L respectively.

CONCLUSIONMonoamine neurotransmitters may be a direct objective evaluating indices. Sugar, glycerinate and cholesterol may be an indirect objective indices.

Adult ; Blood Glucose ; analysis ; Cholesterol ; blood ; Female ; Humans ; Male ; Middle Aged ; Neurotransmitter Agents ; blood ; Occupational Diseases ; metabolism ; Stress, Psychological ; metabolism

AIMTo observe the effect of Xiaoyao Powder on the content changes of CRF mRNA in relative brain zone (hypothalamus, pituitary, hippocampus, cortex) in chronic restrained stress rats.

METHODSRT-PCR and graphic analysis methods were applied to test the content changes of CRF mRNA in relative brain zone.

RESULTSThe CRF-1 gene expression in hypothalamus was modulated lower in stress group and the difference was significant when compared with control group (P < 0.01). The gene expression of CRF-1 in Xiaoyao Powder group was markedly modulated lower in hypothalamus, but it was markedly modulated higher in cortex as compared with control group (P < 0.01). The gene expression of CRF-2 in Xiaoyao Powder group was higher in hypothalamus than that in stress group (P < 0.01), and it was also higher in hippocampus as compared with that in control and stress group (P < 0.01, P < 0.05 respectively).

CONCLUSIONThe modulation point of Xiaoyao Powder group on central neuropeptide of chronic restrained stress is respectively hypothalamus, pituitary, hippocampus and cortex. The modulating target is hypothalamus, the limbic system and the cortex center. It can be suggested that medicine of smoothing the liver simultaneously have poly-target and dual-modulating action and been involved in the integration function of nerve-endocrine-immune net.

Animals ; Brain ; metabolism ; Corticotropin-Releasing Hormone ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Stress, Physiological ; genetics ; Stress, Psychological ; genetics ; metabolism

AIMTo study the role of NO in the midbrain periaqueductal gray (PAG) in the development of stress-induced hypertension (SIH).

METHODSThe model of stress-induced hypertension (SIH) rat was established by electric-foot in company with noise, NADPH-d histochemistry technique was used to investigate the change of nitric oxide synthase (NOS) positive neurons. Selecting and using microinjection and radioimmunoassay, we studied the effects of blood pressure and the content of Ach in rostral ventrolateral medulla (RVLM) after microinjection of L-NNA into PAG.

RESULTS(1) The blood pressure increased, the cell number decreased and the grey degree value increased for the NOS positive neurons of PAG dorsolateral subdivision in SIH rats, and the content of Ach increased in RVLM. (2) Following microinjection of 100 mmol/L 0.1 microl L-NNA into PAG, the mean arterial pressure (MAP) and the content of Ach in RVLM increased in control rats, whereas the change of MAP was significantly smaller in SIH rats than control.

CONCLUSIONThe plastic change of NOS positive neurons of PAG in SIH rats may be involved in the development of SIH, which may be mediated by Ach in RVLM.

Animals ; Blood Pressure ; Hypertension ; etiology ; metabolism ; physiopathology ; Male ; Neurons ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Periaqueductal Gray ; metabolism ; Rats ; Rats, Wistar ; Stress, Psychological

OBJECTIVES: This study was conducted to determine the appropriate sampling time of the salivary stress markers, chromogranin A (CgA) and cortisol as objective indices of job stress assessment in adult females. METHODS: The subjects were 20~39-year-old women (13 office workers, 11 sales-service workers, and 11 college students) who were eligible for the study and free of acute and chronic medical conditions. Salivary CgA and cortisol levels were determined by enzyme-linked immunosorbent assay (ELISA). Saliva samples were collected (2ml each) at 7:00, 8:00, 10:30, 12:00, 17:30, and 22:30 on a typical day. Salivary CgA and cortisol levels, according to sampling time, were compared among the three groups using general linear model. The full version of the Korean Occupational Stress Scale (KOSS), which includes socioeconomic characteristics, health behavior, work-related characteristics, and BMI, was used to access the subjects' job stress. Multiple regression analysis of the job stressors identified by the KOSS was performed on salivary CgA and cortisol levels. RESULTS: The salivary CgA level peaked at 7:00 (time of awakening), then decreased and were maintained at a low level throughout the day, and increased slightly at 17:30. The salivary cortisol level increased steeply within the 1st hour after awakening, followed by a gradual decrease by 12:00, and was then maintained at a low level throughout the day. The salivary cortisol levels of subjects who worked < or =5 days per week and graduated from the university were significantly lower at 8:00 (p=0.006). The salivary cortisol levels of non-smokers were significantly lower at 7:00 (p=0.040) and 8:00 (p=0.003) compared to smokers. There were no significant differences in salivary CgA and cortisol levels at 10:30 and 12:00 in general characteristics. The regression coefficients on salivary CgA level were significant with interpersonal conflict at 17:30 and job insecurity at 22:30. Regression coefficients on salivary cortisol level were significant with organizational system and total job stressors at 17:30. CONCLUSIONS: We suggest that the appropriate sampling times for the salivary stress markers, CgA and cortisol, are at 7:00 (time of awakening), 8:00 (1 hour after awakening), 17:30 (early evening), and 22:30 (before sleep).
Adult ; Biological Markers/metabolism ; Chromogranin A/*metabolism ; Circadian Rhythm ; Female ; Humans ; Hydrocortisone/*metabolism ; Korea ; Saliva/*metabolism ; Stress, Psychological/diagnosis/etiology/*metabolism ; Workplace/*psychology ; Young Adult

OBJECTIVETo observe the effects of Shuyu Ningxin Recipe (SNR) on the praxiology and the expressions of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) of model rats with chronic stress-induced depression, thus exploring its anti-depression mechanisms.

METHODSSixty adult SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the fluoxetine group, the high dose SNR group, the medium dose SNR group, and the low dose SNR group, 10 in each group. All rats were subjected to establish chronic stress-induced depression model for 21 consecutive days. Except those in the normal control group, rats in the rest groups received gastrogavage from the 22nd day. Mice in the model group were administered with normal saline by gastrogavage. SNR at 25.0, 7.5, and 2.5 g/kg was respectively administered to rats in the high dose SNR group, the medium dose SNR group, and the low dose SNR group by gastrogavage. Fluoxetine suspension (12 mg/kg) was given to rats in the fluoxetine group by gastro-gavage. All medication lasted for 3 successive weeks. The weight, open-field test, and the immobility time in forced swimming test were determined before modeling, 3 weeks (after successful modeling), and 6 weeks (by the end of medication). The expressions of hippocampal BDNF and TrkB were measured after the brain tissues were drawn by the end of the experiment.

RESULTSCompared with the normal control group, the body weight grew slowly, the behavior index decreased, the immobility time in forced swimming test was prolonged, and the expressions of BDNF and TrkB were weaken in the model group (P <0.05, P <0.01).The body weight increased, the behavior was improved, the immobility time in forced swimming test was shortened, and the expressions of BDNF and TrkB were enhanced in the high dose SNR group and the fluoxetine group by the and of medication, showing statistical difference when compared with the model group (P <0.05, P <0.01).

CONCLUSIONSNR could exert anti-depression by improving the expression levels of hippocampal BDNF and TrkB.

Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism ; Stress, Psychological ; metabolism