Restraint water-immersion stress (RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala (CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress (RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition, RWIS, but not RS, induced the activation of corticotropin-releasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers. This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.
Action Potentials ; drug effects ; physiology ; Analysis of Variance ; Animals ; Central Amygdaloid Nucleus ; pathology ; Corticotropin-Releasing Hormone ; metabolism ; Disease Models, Animal ; Gastric Mucosa ; pathology ; Gene Expression Regulation ; physiology ; Neurons ; physiology ; Patch-Clamp Techniques ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar ; Stress, Physiological ; physiology ; Stress, Psychological ; etiology ; physiopathology

Helicobacter pylori infection is related to the development of gastric diseases. Our previous studies showed that high thioredoxin-1 (Trx1) expression in H. pylori can promote gastric carcinogenesis. To explore the underlying molecular mechanisms, we performed an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis of stomach tissues from Mongolian gerbil infected with H. pylori expressing high and low Trx1. Differences in the profiles of the expressed proteins were analyzed by bioinformatics and verified using Western blot analysis. We found three candidate proteins, 14-3-3α/β, glutathione-S-transferase (GST), and heat shock protein 70 (HSP70), in high Trx1 tissues compared with low Trx1 tissues and concluded that cellular stress and redox activity-related proteins were involved in the pathogenesis of gastric cancer associated with H. pylori Trx1.
14-3-3 Proteins/physiology* ; Animals ; Computational Biology ; Gerbillinae ; Glutathione Transferase/physiology* ; HSP70 Heat-Shock Proteins/physiology* ; Helicobacter Infections/complications* ; Helicobacter pylori ; Oxidation-Reduction ; Stomach Neoplasms/etiology* ; Stress, Physiological ; Thioredoxins/physiology*

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized mainly by motor dysfunction resulting in bradykinesia, rigidity, tremor, gait impairment, and postural instability. The classic pathogenic feature of PD is preferential loss of dopaminergic neurons in the substantia nigra. Downregulation of rRNA transcription is one of major mechanisms to maintain cellular homeostasis under stress conditions. Nucleolar stress has emerged as a component of the degenerative process caused by impaired rRNA transcription and altered nucleolar integrity. Recent study has indicated that the response to stress conditions and quality control mechanisms are impaired in PD, and that metabolic stress may be a trigger mechanism for PD. This review aims to present evidence for a role of nucleolar stress in PD and has summarized mechanisms by which nucleolar stress may play a role in the progression of PD.
Cell Nucleolus ; physiology ; Humans ; Parkinson Disease ; etiology ; physiopathology ; RNA, Ribosomal ; genetics ; Signal Transduction ; Stress, Physiological ; TOR Serine-Threonine Kinases ; physiology

OBJECTIVETo investigate the clinical value of Physiologic Ability and Surgical Stress (E-PASS) and modified Estimation of Physiologic Ability and Surgical Stress (mE-PASS) scoring systems in predicting the mortality and surgical risk of gastric cancer patients, and to analyze the relationship between the parameters of E-PASS and early postoperative complications.

METHODSClinical data of 778 gastric cancer patients who underwent elective surgical resection in Tianjin Medical University General Hospital from Jan. 2010 to Jan. 2014 were analyzed retrospectively. E-PASS and mE-PASS scoring systems were used to predict the mortality of gastric cancer patients, respectively. Univariate and unconditioned logistic regression analyses were performed to assess the relationships between nine parameters of E-PASS system and early postoperative complications.

RESULTSE-PASS and mE-PASS systems were used to predict the mortality in the death group and non-death group. The Z value was -5.067 and -4.492, respectively, showing a significant difference between the two groups (P<0.05). AUCs of mortality predicted by E-PASS and mE-PASS were 0.926 and 0.878 (P>0.05), and the prediction calibration of postoperative mortality showed statistically non-significant difference (P>0.05) between the E-PASS and mE-PASS prediction and actual mortality. Univariate analysis showed that age, operation time, severe heart disease, severe lung disease, diabetes mellitus, physical state index and ASA classification score are related to postoperative complications (P<0.05 for all). Unconditioned logistic regression analysis showed that severe lung disease, diabetes mellitus, ASA classification score and operation time are risk factors for early postoperative complications (P<0.05 for all).

CONCLUSIONSBoth mE-PASS and E-PASS scoring system have good consistency in the predicting postoperative mortality and actual mortality, and both are suitable for clinical application. Moreover, the mE-PASS scoring system is clinically more simple and convenient than E-PASS scoring system. Preoperative severe lung disease, diabetes mellitus, ASA classification score and operation time are independent factors affecting the early postoperative complications.

Age Factors ; Area Under Curve ; Diabetes Complications ; Elective Surgical Procedures ; Homeostasis ; Humans ; Lung Diseases ; complications ; Operative Time ; Postoperative Complications ; etiology ; mortality ; Postoperative Period ; Predictive Value of Tests ; Regression Analysis ; Retrospective Studies ; Risk Assessment ; methods ; Risk Factors ; Stomach Neoplasms ; mortality ; physiopathology ; surgery ; Stress, Physiological

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the alpha1-adrenergic receptor (alpha1-AR) and beta2-adrenergic receptor (beta2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of alpha1-AR and beta2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1beta, IL-6 and IL-8 were detected after pretreatment with the alpha1/beta2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, alpha1-AR and beta2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of alpha1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of alpha1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1beta, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an alpha1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
Adrenergic alpha-1 Receptor Antagonists/*therapeutic use ; Animals ; Cells, Cultured ; Cytokines/immunology ; Fibroblasts/immunology/pathology ; Humans ; Lipopolysaccharides/administration & dosage/immunology ; Male ; Periodontal Ligament/cytology/immunology/pathology ; Periodontitis/*drug therapy/*etiology/immunology/pathology ; Phentolamine/*therapeutic use ; Rats ; Rats, Wistar ; Receptors, Adrenergic, alpha-1/analysis/*immunology ; Signal Transduction/drug effects ; *Stress, Physiological/drug effects ; Tyrosine 3-Monooxygenase/analysis/immunology

OBJECTIVETo investigate the relationship between emotional status, cold-dry environment and long-term immune responses to the stressors, and the potential pathological mechanisms between causative factors of abnormal Savda syndrome (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to identify the optimal ASS animal model for further studies on traditional Uighur therapeutical formulations.

METHODSSixty mice were randomly and equally divided into 4 groups: control and 3 stress groups. The cold-dry environment was applied by keeping the mice in a climatic chamber. The emotional stress was induced by the application of the repeated electric foot-shocks in the electric foot-shock apparatus. The mice of the combined stress group underwent the repeated electric foot-shock treatment before being housed in the climatic chamber. The experimental routine was repeated for 21 days. In order to look into endocrine and immune stress responses, ELISA was used to determine the serum levels of the hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), Beta-endorphin (β-END) and corticosterone (CORT), of the cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α), and of the immunoglobulins immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG). Lymphocyte subsets were analyzed in duplicate in order to determine differences in the T cell ratio.

RESULTSIn the cold-dry environment group, the serum levels of CRH, ACTH and CORT were significantly higher than those of the control group, whereas serum β-END was not found significantly different. In both the repeated electric foot-shock group as well as in the combined stress group the serum levels of CRH, ACTH, β-END and CORT were significantly higher. Compared to the control animals, the serum concentration of INF-γ was significantly lower in all three different stress groups. The serum level of IL-2 was decreased in the combined stress group whereas the serum TNF-α level was significantly higher. The serum IgG level was significantly higher in all three stress groups, whereas the IgA level was lower in both chronic electric foot-shock group and combined stress group. The IgM level was found significantly higher in the combined stress group only. The percentage of CD4(+) cells in peripheral blood was dramatically decreased in mice exposed to colddry environment, chronic electric foot-shock and combined stress, whereas the percentage of the CD8(+) subset was not significantly different. The CD4(+)/CD8(+) ratios were markedly lower in both cold-dry environment group and combined stress group.

CONCLUSIONSCombined stress can cause hyperactivity of the HPA axis, and an imbalance in the Th1/Th2 cell subset may contribute to illustrate the partial pathological mechanisms of ASS. This study identified this animal model of a combination of physical and emotional stress as an optimal model for further studies on ASS and relative therapies.

Animals ; Chronic Disease ; Cold Temperature ; Disease Models, Animal ; Emotions ; physiology ; Endocrine System ; physiology ; Immunity, Innate ; physiology ; Male ; Medicine, East Asian Traditional ; Mice ; Mice, Inbred ICR ; Stress, Physiological ; physiology ; Stress, Psychological ; etiology ; immunology ; psychology ; Syndrome ; Water-Electrolyte Imbalance ; complications ; immunology

OBJECTIVE: To detect the expression of miR-16 in the hippocampus of a rat depression model induced by maternal deprivation, and to explore whether miR-16 is involved in the pathological process of maternal deprivation-induced depression. METHODS: Newborn SD rats were randomly divided into a maternal deprivation group (n=17) and a control group (n=17). Rats in the maternal deprivation group experienced maternal deprivation for 6 h per day from 1st to 14th postnatal day, while rats in the control group rats received no treatment. When the rats were 13 weeks old, depression-like behaviors were assessed by forced swimming test and sucrose consumption test, and the expression of hippocampal miR-16 in rats was detected by real-time RT-PCR. RESULTS: Maternal-deprived rats exhibited significantly longer passive floating time and lower sucrose preference rate than rats in the control group (P<0.05). Maternal-deprivation rats expressed higher level of miR-16 in the hippocampus than rats in the control group, and the expression level of miR-16 was significantly associated with the passive floating time (r=0.65, P<0.05) and the sucrose preference rate (r=-0.59, P<0.05). CONCLUSION Maternal deprivation can induce depressive behaviors in rats and increase the expression of miR-16 in the hippocampus in rats. MiR-16 may be involved in the pathological mechanism of the maternal deprivation-induced depression.
Animals ; Animals, Newborn ; Depression ; etiology ; genetics ; Hippocampus ; metabolism ; Male ; Maternal Deprivation ; MicroRNAs ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; physiology

OBJECTIVE: To observe the change of serum homocysteine (Hcy) and anti-citrullinated peptide (CCP) antibody concentration in depression rat model induced by chronic unpredictable mild stress (CUMS), and to explore the immunologic mechanism of depression and the relation between depression and its autoimmunity. METHODS: Sixty adult male SD rats were randomly divided into 2 groups, 30 rats in each group, which were divided into 3 subgroups: a normal control group, a model group and a fluoxetinetreated group. The depression rat model was established under CUMS and seperated feeding, after which, open field, sugar consumption and forced swimming test were applied in the first group. After the blood was taken in the second group of rats through heart puncture, the level of serum Hcy was detected by enzymatic cycling assay and serum anti-CCP antibody by ELISA. RESULTS: Compared with the control group and the fluoxetine treatment group, spontaneous activity and sucrose consumption and preference percentage of the rats in the model group significantly reduced, while the immobility time in forced swimming test and the level of Hcy and anti-CCP antibody in the rat serum significantly increased. CONCLUSION Immunity inflammation and autoimmune reaction exist in CUMS depression model rats, and fluoxetine treatment can improve these immune response.
Animals ; Autoantibodies ; blood ; Depression ; drug therapy ; etiology ; immunology ; Disease Models, Animal ; Fluoxetine ; therapeutic use ; Homocysteine ; blood ; Male ; Peptides, Cyclic ; immunology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; immunology

Animals ; Depression ; etiology ; metabolism ; Frontal Lobe ; metabolism ; Glutamic Acid ; metabolism ; Male ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Stress, Physiological ; physiology ; Swimming

The present study was to investigate the role of dopamine D1 receptors and its relationship with glutamate, N-methyl-D-aspartic acid (NMDA) receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in depression induced by chronic unpredictable mild stress (CUMS). CUMS-induced depression model was established in Sprague-Dawley rats, and intrahippocampal microinjections of D1 dopamine receptor agonist SKF38393, non-competitive NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX were respectively adopted by rat brain stereotaxic coordinates. The behavioral observations were conducted by measurement of weight changes, sucrose preference test, open-field test and tail suspension test. The concentration of glutamic acid and the expression of its receptors' subunits were detected by HPLC and Western blot, respectively. The results showed that, compared with control group, CUMS rats showed depression-like behavioral changes, higher concentration of glutamic acid, lower expressions of NMDA receptor (NR1) and AMPA receptor (GluR2/3) in hippocampus. Pretreatment with injection of SKF38393 could rescue such depression effect of CUMS, decrease the concentration of glutamic acid, and increase the expressions of NMDA receptor (NR1), AMPA receptor (GluR2/3) in hippocampus. Pretreatment with MK-801 could enhance the antidepressant effect of SKF38393, while NBQX weakened. These results suggest that agonists of D1 dopamine receptor could reduce the concentration of glutamic acid in hippocampus, and its antidepressant effect may be mediated by AMPA receptor partially.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Animals ; Depression ; etiology ; physiopathology ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; Glutamates ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; metabolism ; Receptors, Dopamine D1 ; agonists ; physiology ; Stress, Physiological ; physiology