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

Breast cancer is a major chronic disease threatening women's health. It has topped the global cancers as the diagnosed cases outnumbered lung cancer patients in 2020. Internal damage due to the seven emotions is an important cause of breast cancer and the disorders of hypothalamic-pituitary-adrenal(HPA) axis and endocrine system and the abnormal immune defense mechanism in response to psychological stress all affect the occurrence and development of breast cancer. It is noteworthy that the theory of seven emotions in traditional Chinese medicine and the psychological stress theory of modern medicine have something in common in some aspects. Therefore, this study explored the correlation between internal damage due to the seven emotions and psychological stress and analyzed the molecular biological mechanisms of psychological stress influencing breast cancer from the perspective of modern medicine, which is helpful to reasonably prevent breast cancer and other related tumors and improve the prognosis of breast cancer patients through emotion regulation.
Breast Neoplasms/genetics* ; Emotions ; Female ; Humans ; Hypothalamo-Hypophyseal System ; Medicine, Chinese Traditional ; Pituitary-Adrenal System ; Stress, Psychological

OBJECTIVETo observe the effects of acute immobilization stress on the mRNA expression of tyrosine kinase B (TrkB) in rats' hippocampus.

METHODSEighteen SD rats were randomly divided into three groups, i.e., the normal control group, the model group, and the medication group, 6 in each group. The acute immobilization stress model was prepared in the model group using acute immobilization for 2 h. Ginsenoside Rb1 (40 mg/kg) was peritoneally injected to rats in the medication group 30 min before modeling, with the same procedure as those for rats in the model group. No treatment was performed to rats in the normal control group. The plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) contents were detected using ELISA. The mRNA expression of TrkB in the rats' hippocampus was detected using real-time fluorescence quantitative RT-PCR.

RESULTSBefore modeling there was no statistical difference of plasma CORT or ACTH concentrations among three groups (P >0.05). The plasma CORT and ACTH concentrations increased in the model group and the medication group more significantly after modeling than before modeling, showing statistical difference (P <0.05). Besides, they were obviously higher in the model group than in the normal control group (P <0.05). They were obviously higher in the medication group than in the model control group (P <0.05). Compared with the normal control group, the mRNA expression of TrkB significantly decreased in the model group (87.73 +/- 7.62 vs 50.65 +/- 5.19, P < 0.05), showing statistical difference. The mRNA expression of TrkB was significantly higher in the medication group (78.91 +/- 18.07) than in the model group, showing statistical difference (P <0.05).

CONCLUSIONPretreatment by ginsenoside Rb1 could increase the plasma CORT and ACTH concentrations, maintain the mRNA expression of TrkB, thus relieving injury induced by acute immobilization stress.

Adrenocorticotropic Hormone ; blood ; Animals ; Corticosterone ; blood ; Ginsenosides ; pharmacology ; Hippocampus ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; genetics ; metabolism ; Stress, Psychological ; metabolism

OBJECTIVETo find out whether tumor necrosis factor (TNF)-alpha-308 and TNF-alpha-238 locus (G-->A) mutation within the TNF-alpha gene promoter region is associated with susceptibility to occupational stress.

METHODS169 pipelining workers were investigated using the occupational stress measuring instrument. The subjects were divided into high and low strain groups according to the job strain score of the questionnaire. By means of polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha gene polymorphisms of all subjects were analyzed.

RESULTSThere were 34 workers with genotype -308G/G and 4 with -308G/A genotype in the low strain group while in the high strain group, there were 117 workers with genotype -308G/G and 10 with -308G/A genotype and 1 with -308A/A. No significant difference in -308 genotype was found between the two groups (chi2 = 0.0001, P > 0.05). There were 30 workers with genotype -238G/G and 7 with -238G/A genotype and 1 with -238A/A in the low strain group while there were 118 workers with genotype -238G/G and 10 with -238G/A genotype in high strain group. The frequencies of TNF-alpha-238A in the low strain groups were significantly higher than that in high strain groups (chi2 = 5.45, P < 0.05).

CONCLUSIONTNF-alpha promoter G238A polymorphism is associated with occupational stress. There is no evident relationship between TNF-alpha promoter G308A polymorphism and susceptibility to occupational stress.

Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Occupational Diseases ; psychology ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Stress, Psychological ; genetics ; Surveys and Questionnaires ; Tumor Necrosis Factor-alpha ; genetics

The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1β, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1β, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
Animals ; Antidepressive Agents ; Behavior, Animal ; Chromatography, Liquid ; Depression/etiology* ; Disease Models, Animal ; Drugs, Chinese Herbal ; Hippocampus ; Mice ; Molecular Docking Simulation ; Sirtuin 1/genetics* ; Stress, Psychological ; Tandem Mass Spectrometry

OBJECTIVETo explore association between GR and ACTHR gene polymorphisms and quantitative trait of stress in Chinese Han population.

METHODSFour polymorphic markers (GRA5556G, A5556G, GAGG4534/4536AAAG, promoter T-2C) in GR gene and ACTHR gene were genotyped with PCR-RLFP in 200 healthy Hans. ISTA6.0 and life event stressor questionnaire was used to assess stressors. JSS, SCL-90 and GWB questionnaires were used to quantify the phenotypes of stress. Blood cortical and ACTH levels, and nervous behavior function were measured to assess Physiological strain. CWAI questionnaire was used to assess work ability. Then strain was assessed with Structural equation modeling (SEM).

RESULTSThe subjects with GR A5556G genotype (G/A) showed significantly higher plasma cortisol levels, higher psychological stress scores, lower work ability scores and lower plasma ACTH levels compared with the subjects with wild-type (P < 0.01). Psychological stress scores and plasma cortisol levels in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly higher than those in the subjects with wild-type, but the reaction and action sensitivity in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly lower than those in ones with wild-type (P < 0.01). The ACTH level in the subjects with ACTHR promoter T-2C T/T genotype was significantly lower than that in ones with C/C and C/T genotype (P < 0.01). Interaction of GRA5556G and GG4534/4536AAAG with plasma cortisol was positively associated (βs = 0.543, P < 0.01), but with SCL-90 score was negatively associated (βs = -0.374, P < 0.01). Interaction of GRA5556G and GGC6294G with plasma cortisol was correlated (βs = 0.465, P < 0.05). While GR and ACTHR gene variants are the risk factors for psychological strain, physiological strain and decreased work ability (βs are 0.62, 0.43, -0.74, respectively (P < 0.01). While scarce social support, job stressors, negative life stressors and dangerous individual characters are the risk factors for occupational strain, psychological strain, physiological strain and decreased work ability (P < 0.01).

CONCLUSIONGRA5556G, GRA5556G, GAGG4534/4536AAAG and ACTHR promoter T-2C variants might be associated with quantitative trait of strain, and GR and ACTHR gene variants with stressors increased the risk for developing strain.

Asian Continental Ancestry Group ; genetics ; Genotype ; Humans ; Life Change Events ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Corticotropin ; genetics ; Receptors, Glucocorticoid ; genetics ; Social Support ; Stress, Psychological ; epidemiology ; genetics ; Surveys and Questionnaires ; Workload

The aim of this study was to investigate the influence of neonatal isolation stress on hyperlocomotion in complexin II knockout mouse (Cplx2(-/-)). The mice were randomly divided into 4 groups: Cplx2(-/-) with stress, Cplx2(+/+) with stress, Cplx2(-/-) without stress and Cplx2(+/+) without stress. Isolation stress was employed on the pups of stress groups from the 2nd day after the postnatal to the 21st day. The PCR was used to determine the gene type and the hyperlocomotion test was employed to detect the change of animal behavior after methamphetamine or saline injection (i.p.). The results showed that the animals of all groups increased their movement after injection of 0.2 mg/kg methamphetamine in different levels (P < 0.01), compared with those injected with saline. The Cplx2(-/-) mouse with stress revealed a significant increase in the distance of free movement after injection of 0.2 mg/kg methamphetamine compared with the knockout mouse without stress (P < 0.001). When Cplx2(-/-) mouse with stress was compared with wild type with stress, Cplx2(-/-) mouse with stress had more movement (P < 0.001), indicating that Cplx2 has effect on the hyperlocomotion as well. These results suggest an involvement of stress and Cplx2 in the movement behavior of mice.
Adaptor Proteins, Vesicular Transport ; genetics ; Animals ; Animals, Newborn ; Behavior, Animal ; physiology ; Locomotion ; physiology ; Methamphetamine ; pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Mutant Strains ; Nerve Tissue Proteins ; genetics ; Social Isolation ; Stress, Psychological ; psychology

OBJECTIVETo study the interactive effect of job stress and genetic susceptibility (or gene polymorphism) on hypertension.

METHODSA cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. beta2-AR genotypes and allele frequencies at amino acid positions 16 (beta2-AR-16: Arg-->Gly) and 27 (beta2-AR-27: Gln-->Glu) were identified by PCR-RFLP.

RESULTSJob stress was related with the prevalence of hypertension in males (P < 0.05), whereas no significant relationship was found in females (P > 0.05). Differences in genotypes and allele frequencies of the beta2-AR-16 were statistically significant between the hypertension and control groups (P < 0.05), whereas those of beta2-AR-27 were not (P > 0.05). The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group (P < 0.01 or 0.05).

CONCLUSIONHigh job stress and polymorphism of beta2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

Adult ; China ; epidemiology ; Employment ; psychology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Polymorphism, Genetic ; Power Plants ; Prevalence ; Receptors, Adrenergic, beta-2 ; genetics ; Stress, Psychological ; complications ; Young Adult

OBJECTIVETo observe the changes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit and related regulatory protein mRNA expression in the hippocampus and amygdala in immobilization stressed rats and effect of Xiaoyaosan (XYS) on them.

METHODSImmobilization model rats were established by binding for 3 h per day and intervened with XYS, the expression of AMPA receptor subunit (GluR1-4), N-ethylmaleimide sensitive factor (NSF) and protein interacting with C-kinase 1 (PICK1) mRNA expression in model rats' CA1 and CA3 regions of hippocampus, dentate gyrus and amygdala were detected on day 7 and day 21 after modeling.

RESULTSOn day 7, expression of GluR1 mRNA was significantly decreased in CA1 region (P < 0.05) and increased in CA3 region and amygdala (all P < 0.05); expression of GluR2 and GluR3 mRNA in amygdala (all P < 0.05) and GluR4 mRNA in CA1 region (P < 0.01) significantly increased, but the expression of NSF and PICK1 mRNA in amygdala only showed an increasing trend. XYS showed effective regulation on GluR4 mRNA in CA1 region (P < 0.01) and GluR1-3 mRNA expression (P < 0.05, P < 0.01) in amygdala. On day 21, the expression of GluR4 mRNA in CA1 region (P < 0.05) and GluR2 mRNA in dentate gyrus (P < 0.05) markedly lowered and expression of GluR1 mRNA in amygdala increased (P < 0.01); XYS significantly regulated the expression of GluR1 and GluR4 mRNA in CA1 region (all P < 0.05).

CONCLUSIONRepeated stress in a short time shows effect on expression of AMPA receptor subunit mRNA stronger than chronic stress. The regulation of XYS to AMPA receptor subunit mRNA expression were obvious in hippocampal CA1 region and amygdala.

Amygdala ; drug effects ; metabolism ; Animals ; Carrier Proteins ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; Hippocampus ; drug effects ; metabolism ; Male ; N-Ethylmaleimide-Sensitive Proteins ; genetics ; Nuclear Proteins ; genetics ; Protein Subunits ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; genetics ; Restraint, Physical ; Reverse Transcriptase Polymerase Chain Reaction ; Stress, Psychological ; physiopathology

BACKGROUNDBrain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats.

METHODSForty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry.

RESULTSAge and stress had different effects on the behavior of different aged animals (age: F = 6.173, P < 0.05, stress: F = 6.056, P < 0.05). Stress was the main factor affecting sucrose preference (F = 123.608, P < 0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P < 0.05). The older stress rats showed a lower sucrose preference than young stress rats (P < 0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P < 0.05), exhibiting fewer vertical movements (P < 0.05) and less grooming (P < 0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P < 0.05), a reduction that was still present at the eighth day after stress (P < 0.05). Stress and age were the main factors affecting the expression of BDNF (F = 9.408, P < 0.05; F = 106.303, P < 0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point.

CONCLUSIONStress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.

Age Factors ; Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; analysis ; genetics ; Chronic Disease ; Dentate Gyrus ; chemistry ; Exploratory Behavior ; Hippocampus ; chemistry ; Immunohistochemistry ; Rats ; Rats, Wistar ; Stress, Psychological ; metabolism ; psychology ; Sucrose ; administration & dosage