Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Role of HPA Axis Dysregulation in Cancer-related Fatigue Based on Principle of "Treating Overstrain with Warming" / 中国实验方剂学杂志

This paper discusses the theoretical basis of traditional Chinese medicine （TCM） for the treatment of cancer-related fatigue （CRF） based on the principle of treating overstrain with warming in the Huangdi's Internal Classic 《黄帝内经》 and the role of hypothalamic-pituitary-adrenal （HPA） axis dysregulation in CRF， aiming to provide new ideas for the clinical treatment of CRF. In the pulsatile regulation of the HPA axis， cortisol， which is synthesized and released by the adrenal cortex， plays an essential role in the life activities. The abnormal circadian rhythm and reduced serum level of cortisol are major factors leading to CRF. Therefore， increasing the serum level and stimulating the biological activity of cortisol and restoring the normal function of HPA axis are important targets for the treatment of CRF and also the key to the TCM treatment of this disease. According to the TCM principle of treating overstrain with warming， we interpreted the etiology and clinical manifestations of overstrain and further explored the causes of CRF. It is believed that the depletion of Qi and blood， Yin and Yang， and fluid in the kidney， spleen， and liver is the key of the disease， which results in symptoms such as fatigue. Further， we elaborated on the theoretical connotation of warming and summarized the two main treatment principles of tonifying with warm-natured herbs and relieving fever with sweet- and warm-natured herbs. According to the different characteristics of the organs affected by pathogen， we proposed the treatment method of warming kidney to cultivate essence， warming stomach and nourishing spleen to replenish Qi， nourishing liver and tonifying blood to promote Qi movement， and relieving fever with sweet- and warm-natured herbs to alleviate fatigue. The warming method can elevate the serum level and invigorate the biological functions of cortisol in CRF patients， which provides a new theoretical basis for alleviating the symptoms and improving the quality of life of cancer patients in clinical practice.

Antidepressant Effects of Oligosaccharides and Polysaccharides in Chinese Medicine： A Review / 中国实验方剂学杂志

Depression is a common psychiatric disease that seriously affects the physical and mental health and quality of life of patients， and has become one of the major global disease burdens. The etiology of depression is intricate， and despite extensive research， its pathogenesis remains inconclusive， resulting in various hypotheses of its onset mechanisms. Presently， the primary approach for clinically treating depression involves the utilization of selective inhibitors targeting the reuptake of monoamine neurotransmitters within the central nervous system. However， these drugs are generally characterized by delayed onset of action， limited efficacy and obvious resistance. Recently， researchers have gradually turned their attention to the development of antidepressant drugs with novel mechanisms. Notably， as a category of abundantly available active ingredients in Chinese medicine， numerous pharmacological studies have demonstrated that oligosaccharides and polysaccharides possess promising antidepressant properties， such as Morindae Officinalis Radix oligosaccharides， Polygalae Radix oligosaccharide esters， Poria polysaccharides and Astragali Radix polysaccharides. Their pharmacological mechanisms are various， including enhancing the levels of monoamine neurotransmitters in the brain， inhibiting the hyperactivation of the hypothalamic-pituitary-adrenal axis（HPA axis）， increasing the expression of neurotrophic factors（NTF）， regulating immune-inflammatory responses and modulating the microbiota-gut-brain axis. Therefore， oligosaccharides and polysaccharides from Chinese medicine have become a vital source of safe and effective novel antidepressant candidates due to the potential to improve depression through integrated regulatory effects. This article aims to provide a comprehensive and systematic review of recent progress to contribute to the elucidation of the mechanisms underlying the antidepressant effects of oligosaccharides and polysaccharides derived from Chinese medicine.

Relation between testosterone, cortisol and aggressive behavior in humans: a systematic review / Relação entre testosterona, cortisol e comportamento agressivo em humanos: uma revisão sistemática / Relación entre testosterona, cortisol y comportamiento agresivo en humanos: una revisión sistemática

Aggression is an evolutionary behavior as it has a role in survival, increasing one's access to food, shelter, status and reproduction. Testosterone and Cortisol are hormones often linked to aggressive behavior. We gathered and organized data from the last five years on the relation among Testosterone, Cortisol and aggression, while assessing the methods used by those scientific papers. A systematic review was made according to PRISMA guidelines. The search for indexed articles was performed in January 2019 using the keywords aggress* AND Testosterone AND Cortisol in three databases: Web of Science, SCOPUS and PsycInfo. The specific role of Testosterone and Cortisol in aggressive behavior is not unanimous. However, most articles found either an increase in Testosterone or a decrease in Cortisol associated with this behavior. There is the need for standardizing methods of triggering and assessing aggressive behavior, taking into account the assessment of social desirability and its impacts.

Agressividade é um comportamento evolutivo, tendo um papel na sobrevivência ao aumentar o acesso à comida, abrigo, status social e reprodução. A testosterona e o cortisol são hormônios frequentemente associados a comportamentos agressivos. Este estudo reúne e organiza dados dos últimos cinco anos sobre a relação entre testosterona, cortisol e agressividade, avaliando também os métodos utilizados pelos artigos. Uma revisão sistemática foi conduzida segundo as diretrizes do PRISMA. Uma pesquisa eletrônica de artigos foi realizada em janeiro de 2019, usando as palavras-chave agress* AND Testosterone AND Cortisol em três bancos de dados: Web of Science, SCOPUS e PsycInfo. O papel desses hormônios no comportamento agressivo não é unânime, porém a maioria dos artigos incluídos encontrou um aumento na testosterona ou uma diminuição no cortisol, associados a esse comportamento. Há a necessidade de padronizar os métodos de induzir e de avaliar agressividade, levando em conta a desejabilidade social e seus impactos.

La agresividad es un comportamiento evolutivo, por desempeñar papel en la supervivencia, aumentando el acceso a comida, refugio, estatus social y reproducción. La testosterona y el cortisol son hormonas frecuentemente relacionadas con el comportamiento agresivo. Este estudio reúne y organiza datos de los últimos cinco años sobre la relación entre testosterona, cortisol y agresividad, junto a los métodos de evaluación utilizados por los artículos científicos. Se realizó una revisión sistemática de acuerdo con las directrices PRISMA. La búsqueda electrónica de artículos indexados fue realizada enero de 2019, utilizándose de las palabras clave aggress* AND Testosterone AND Cortisol en tres bases de datos: Web of Science, SCOPUS y PsycInfo. El papel de esas hormonas en el comportamiento agresivo no es unánime, aunque la mayoría de los artículos incluídos hayan hallado aumento de testosterona o disminución en cortisol, asociados a ese comportamiento. Se necesita la estandarización de los métodos de inducción y evaluación de la agresividad, teniendo en cuenta la deseabilidad social y sus impactos.

Protective Effect of Total Ginsenoside Ginseng Root on Learning and Memory Impairment and Anxiety in Rats Induced by Hindlimb Suspension / 中国实验方剂学杂志

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （<italic>P</italic><0.05，<italic> P</italic><0.01）， the content of dopamine， acetylcholine， glutamic acid， and <italic>γ</italic>-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and <italic>γ</italic>-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

Effect of Sinisan on BDNF/TrkB， 5-HT/5-HT1AR， and HPA axis in Depression Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg^-1） group， and low- （1.25 g·kg^-1）， medium- （2.5 g·kg^-1）， and high-dose （5 g·kg^-1） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.

Effects of depression and insomnia on HPA axis and amino acid and monoamine neurotransmitters in hypothalamus of rats / 中国药理学通报

Aim To explore the effects of chronic unpredictable mild stress combined with sleep deprivation on the hypothalamic-pituitary-adrenal axis (HPA) and the amino acid and monoamine transmitters in hypothalamus of rats. Methods Chronic unpredictable mild stress combined with modified multi-platform water environment sleep deprivation was used to replicate depression and insomnia rat models. ELISA was used to measure the content of HPA axis related molecules in serum and hypothalamus, the content of amino acid transmitter glutamate (Glu) and GABA in hypothalamus; HPLC-ECD was applied to measure the content of monoamine transmitter NE, 5-HT, DA in hypothalamus; WB and RT-qPCR were employed to measure the expression of GABA related molecules GAD67, GABA

The effect of antidepressant treatment on the HPA axis, changes in depression score and serum levels of TNF-α in depressed infertile women

Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.

Establishment of rat heart-kidney insomnia model consistent with traditional Chinese medicine syndrome and its serum metabolomics / 中国中药杂志

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.

Effect of Tianwang Buxin Pills on Behavior, HPA Axis, BDNF Expression and Phosphorylation of GSK3β in Mice with Chronic Unpredictable Stress / 中国实验方剂学杂志

Objective:To investigate the effect of Tianwang Buxin pills on behavior， hypothalamus pituitary adrenal axis （HPA axis）， hippocampal glycogen synthase kinase 3β （GSK3β） phosphorylation and brain-derived neurotrophic factor （BDNF） expression in mice with chronic unpredictable stress， and explore its mechanisms for antidepressant-like action. Method:Totally 60 male ICR mice were randomly divided into normal group， chronic stress model group， fluoxetine hydrochloride group （10 mg·kg-1） and Tianwang Buxin pills high， middle and low dose groups （3.6， 1.8， 0.9 g·kg-1）. The mice were subjected to the chronic unpredictable stress （CUS） protocol for a period of 28 d to induce depressive-like behavior. Then， a sucrose preference test， open-field test and novelty-suppressed feeding test were performed to detect the behavior changes. The blood， adrenal gland and hippocampus of mice were collected. The contents of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The changes of GSK3β phosphorylation and BDNF expression in hippocampus were detected by Western blot， and the adrenal index was then calculated. Result:As compared with the normal group， the sucrose water preference was significantly decreased （P<0.01）， the number of opening activities was significantly reduced （P<0.05）， the feeding latency of novelty inhibition was prolonged （P<0.01）， the serum ACTH and CORT contents were significantly increased （P<0.05，P<0.01）， GSK3β phosphorylation and BDNF expression levels in hippocampus were significantly decreased （P<0.01）， and adrenal index was significantly increased in model group （P<0.01）. As compared with the model group， Tianwang Buxin pills treatment significantly reversed the CUS-induced behavioral abnormalities in depression model mice （P<0.05， P<0.01）， significantly decreased the levels of plasma ACTH and CORT （P<0.01） and adrenal and adrenal gland index （P<0.01）， while increased GSK3β phosphorylation and BDNF expression in hippocampus （P<0.05， P<0.01）， with its effect similar to that of fluoxetine hydrochloride. Conclusion:Tianwang Buxin pills produced antidepressant-like effects in chronic unpredictable stress mice， and its mechanism may be associated with inhibiting HPA axis activity and up-regulating GSK3β phosphorylation and BDNF protein expression in hippocampus.

Eosinophil Count: Parameter to Assess the Psychological Stress

Human body is endowed with an enormous capacity to cope up with stress. Body’s entire machinery work together to achieve the goal of maintaining the homeostasis. Stressful situations have also become a part of life and both physical and psychological stress are subjected to body response in different ways.Stress is defined as nonspecific response of the body to any demand. Most of the time such stress is psychological one. Aims & Objectives: This study was conducted to see the effect of psychological stress in young students, to evaluate the magnitude of stress under different grades and to identify the students more vulnerable to stress. Methods: The present study was conducted on first year students of Medical College in Meerut. Pulse rate and Eosinophil count were measured of all the students during various periods. Results: Pulse rate was increased significantly in all the subjects of either sex before the examination and Eosinophil count was decreased significantly in all the subjects of either sex. Conclusion: In our study a compare of eosinophil count was made among the students in various phase of psychological stress. All the changes in stress occur probably due to stimulation of sympatho-adrenanl activation via hypothalamo-pituitary-adrenal axis (HPA axis). We must focus on stress-free environment in schools and colleges.

Effect of Guiluerxianjiao on behaviors and HPA axis function in a rat model of post-traumatic stress disorder / 中国药理学通报

To investigate the effects of Guiluerx-ianjiao (GLEXJ) on the change of behaviors and HPA axis function in a rat model of post-traumatic stress disorder ( PTSD ). Methods Single-prolonged stress (SPS) was used to establish the model of PTSD. The level of locomotor activities and anxiety behaviors were assessed by open field test and elevated plus maze test. The hypothalamic-pituitary-adrenal fast negative feedback function was assessed by dexamethasone suppression test. The contents of both plasma CORT and ACTH were measured by ELISA. Results On day 8 after SPS, model group showed enhanced HPA fast negative feedback and continued to day 22. The anxiety level of model group increased on day 8 and lasted on day 29. While on day 29, locomotor activities decreased and plasma CORT content increased. When continuously treated by GLEXJ for 14 days, the enhanced HPA axis negative feedback function was significantly inhibited in GLEXJ group. After 21 days of continuous administration, locomotor activities increased. In addition, the level of anxiety and CORT content were down-regulated in GLEXJ group. Conclusions GLEXJ could mitigate behavior disorder in a rat model of PTSD, which may be related to regulating HPA axis dysfunction.

Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis / O exercício físico pode modular os níveis de cortisol em indivíduos com depressão? Uma revisão sistemática e metanálise

Abstract Introduction: Major depressive disorder (MDD) is a prevalent medical illness that is associated with chronic stress. Patients with MDD can show an imbalance in cortisol levels, which can be restored with the remission of symptoms. Physical exercise training has been used as a tool to promote changes in cortisol levels in healthy individuals. However, it is unknown if exercise can produce the same results in individuals with MDD. Objective: To review evidence of cortisol changes after exercise training in individuals with MDD. Methods: We conducted a search on PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus, and PsycInfo databases. Random effects meta-analysis was performed and standardized mean difference (SMD) effect size was calculated. Analyses of forest and funnel plots was conducted using Stata v.11.0 software. Results: At first, 463 studies were obtained in the search. After completion of the selection procedure, five articles with seven analyses were included. Type of exercise, frequency of training, cortisol measurement, and type of control group were analyzed. There was a reduction of cortisol levels in the exercise group (SMD = −0.65, 95%CI 1.30-0.01). Moreover, sensitivity analysis and subgroup analyses revealed an effect of type (aerobic exercise) and frequency (five times per week) of exercise on reduction of cortisol levels. However, these results should be interpreted cautiously due to the small number of studies and a substantial heterogeneity among them. Conclusion: Physical exercise promotes a reduction in cortisol levels in individuals with MDD. However, this finding can be influenced by type of exercise, weekly frequency, and type of cortisol measurement.

Resumo Introdução: A depressão maior (DM) é uma doença associada ao estresse crônico que pode apresentar um desequilíbrio nos níveis de cortisol, podendo ser recuperado com a remissão dos sintomas. O exercício tem sido utilizado como uma ferramenta para promover mudanças nos níveis de cortisol em indivíduos saudáveis. No entanto, não se sabe se o exercício produz os mesmos resultados em indivíduos com DM. Objetivo: Revisar evidências de alterações dos níveis de cortisol após o exercício em indivíduos com DM. Métodos: Foi realizada busca nas bases de dados PubMed, SciELO, LILACS, ISI Web of Knowledge, Scopus e PsycInfo. Procedeu-se a metanálise com o cálculo do tamanho do efeito da diferença de média padronizada. Foi utilizado o software Stata v.11.0. Resultados: Foram obtidos na busca 463 estudos. Após o procedimento de seleção, cinco artigos com sete análises foram incluídos. O tipo de exercício, frequência de treinamento, tipo de medida do cortisol e tipo de grupo controle foram analisados como subgrupos. Houve uma redução dos níveis de cortisol no grupo de exercício. Além disso, a análise de sensibilidade e análises de subgrupos revelaram um efeito do tipo (exercício aeróbico) e da frequência (cinco vezes por semana) de exercício na redução dos níveis de cortisol. No entanto, esses resultados devem ser interpretados com cautela, devido ao pequeno número de estudos e uma heterogeneidade substancial entre eles. Conclusão: O exercício promove redução dos níveis de cortisol em indivíduos com DM. No entanto, esse achado pode ser influenciado pelo tipo de exercício, medida do cortisol e frequência semanal.

Stress, A Self Generated Problem-an Ayurvedic Approach

In the modern era, the high-tech communication facilities, rapid industrialization, sophisticated life style and extensive use of computers have made lives much easier but they are blamed for making the life stressed. It is estimated that 80% of all modern diseases have their origin in stress. Stress and health are closely linked. Constant exposure to stress leads to psycho-somatic disorders affecting immune, cardiovascular and nervous systems. The diseases linked to stress includes heart disease, asthma, allergies, hypertension, diabetes and even cancer. In view of the changing concepts of health and diseases and with the emergence of modern health hazards, attention has been drawn to the holistic concept of Ayurveda. Ayurveda proclaims that the main purpose of human birth is to attain Purusharthas -Dharma, Artha, Kama and Moksha. To achieve these aims, one needs a healthy body and healthy mind. Ayurveda considers body and mind as inter-related and inter-dependent to each other. Dhi, Dhairya and Atmadi vignynana plays a very important role in the attainment of healthy mind and it in turn contributes a healthy body. Any factor which adversely affects the Sareera, Indriya, Satwa and Athma may lead to ill health either at somatic or psychic level. This review tries to explain how the individuals himself is responsible for stress.

Associations Among Plasma Stress Markers and Symptoms of Anxiety and Depression in Patients with Breast Cancer Following Surgery

OBJECTIVE: The objective of present study is to analyze the prevalence of depression and anxiety following breast cancer surgery and to assess the factors that affect postoperative psychological symptoms. METHODS: The Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Body Image Scale (BIS), and Rosenberg Self Esteem Scale (RSES) were used to assess the psychological states of patients who had been diagnosed with and had undergone surgery for breast cancer. Blood concentrations of the stress markers adrenocorticotropic hormone, cortisol, arginine-vasopressin, and angiotensin-converting enzyme were measured. Pearson’s correlation analysis and multilinear regression analysis were used to analyse the data. RESULTS: At least mild depressive symptoms were noted in 50.5% of patients, while 42.4% of patients exhibited at least mild anxiety symptoms. HAM-D score was positively correlated with HAM-A (r=0.83, p < 0.001) and BIS (r=0.29, p < 0.001) scores and negatively correlated with RSES score (r=-0.41, p < 0.001). HAM-A score was positively correlated with BIS score (r=0.32, p < 0.001) and negatively correlated with RSES score (r=-0.27, p < 0.001). There were no statistically significant associations between stress markers and depression/anxiety. CONCLUSION: Patients with breast cancer frequently exhibit postoperative depression and anxiety, which are related to low levels of self-esteem and distorted body image.

Potassium 2-(1-hydroxypentyl)-benzoate improves depressive-like behaviors in rat model

Potassium 2-(1-hydroxypentyl)-benzoate (PHPB) is a novel drug candidate for acute ischemic stroke. PHPB has been also shown to be beneficial for some neurodegenerative diseases. In this study, we demonstrated that PHPB improved depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Male SD rats were subjected to the stress for five weeks. PHPB (30 and 100 mg/kg) or fluoxetine (FLX 10 mg/kg, as positive control) was administered orally from the third week in CUMS procedure. The behavioral tests were applied and then the biochemical studies were carried out. PHPB or FLX treatment rescued the behavioral deficiency in CUMS-exposed rats. Meanwhile, PHPB normalized the enhanced level of serum corticosterone, improved hippocampal and serum BDNF levels, as well as p-CREB level in hippocampus. In addition, PHPB could reverse the reduced level of extracellular 5-HT and its metabolite 5-HIAA in prefrontal cortex (PFC) of depressed rats. In summary, our results showed that PHPB improved depression-like behaviors in CUMS-exposed rats. The mechanisms might relate to the reverse of neurotrophic disturbance in the brain, reducing excessive HPA axis response and facilitating the release of 5-HT.

Effect of electroacupuncture on HPA axis depended on FKBP5 located in hypothalamic paraventricular nucleus during traumatic stress / 复旦学报（医学版）

Objective To observe hypothalamic-pituitary-adrenal (HPA) axis activity after traumatic stress via electroacupuncture (EA) modulation,and to explore the role of FKBP5 located in hypothalamic paraventricular nucleus (PVN).Methods Sixty male rats were randomly divided into 5 groups (n =12):control,1 day after trauma,3 days after trauma,7 days after trauma and EA intervention.SP-6 and ST-36 EA were applied to the strongest stress group as the intervention in order to observe the recovery of HPA axis.Then the body temperature of each group was measured at the corresponding time points,immunohistochemical staining was used to detect the expressions of c-fos and FOSB in the hypothalamic PVN.The levels of serum hormones were measured by radioimmunoassay.Western blot was used to detect FKBP5 expression Results The body temperature of the rats in the one day trauma group was significantly higher [(37.90 ± 0.21)℃ vs.(37.20 ± 0.25)℃,P＜0.05] than that in the control group,and the expression levels of c-fos (1.00 ± 0.16 vs.2.30 ± 0.22,P＜0.01) and FOSB (1.00± 0.08 vs.2.00± 0.33,P＜0.001) in the hypothalamic paraventricular nucleus also increased significantly.However,compared with the strongest stress group,the serum ACTH (33.80 ± 4.88 vs.28.20 ± 3.31,P＜0.05) and CORT (338.39 ± 29.51 vs.280.85 ± 30.39,P＜0.01) of the intervention group decreased significantly.At the same time,Western blot results showed that FKBP5 (3.30 ± 0.47 vs.2.50 ± 0.42,P＜0.05)expression in hypothalamic PVN was also significantly reduced.Conclusions The activity of HPA axis can reach the highest level 1 day after traumatic stress,and can be significantly down-regulated by EA which may be depended on FKBP5.

Effects of Xiaoyao Kang'ai Jieyu Formula on Depressive Symptoms of Mice with Breast Cancer Related Depression / 中国中医药信息杂志

Objective To investigate the effects of Xiaoyao Kang'ai Jieyu Formula on mice with breast cancer related depression; To explore its mechanism. Methods BALB/c female mice were set as study objects. Subaxillary injection of inflammatory 4T1 cells and intraperitoneal injection of corticosterone were used to establish a model of breast cancer related depression. According to the consumption of sugar water, mice were randomly divided into blank group, model group, paclitaxel group, Xiaoyao Kang'ai Jieyu Formula group, chemotherapy+fluoxetine group, and chemotherapy + Xiaoyao Kang'ai Jieyu Formula group. After 21 days, sucrose preference test, open-field test, and novelty feeding test were performed to detect changes in the behavior of mice in each group. ELISA were used to detected the contents of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in plasma, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), tumor markers carbohydrate antigen CA153, CA125 and carcinoembryonic antigen (CEA) in serum. Results Compared with the blank group, the consumption of sugar, horizontal and vertical movements of mice in the model group significantly decreased (P<0.01, P<0.05); the latency of ingestion significantly increased (P<0.01, P<0.05); the levels of tumor markers CA153, CA125, CEA and some indexes of HPA axis significantly increased (P<0.01); the expressions of monoamine neurotransmitter NE, DA and 5-HT significantly decreased (P<0.01). Compared with the model group, sugar consumption and autonomic activity significantly increased in the chemotherapy + Xiaoyao Kang'ai Jieyu Formula group, and behavioral despair condition was improved (P<0.01, P<0.05); the content of tumor markers and some indexes related to HPA axis significantly decreased (P<0.01, P<0.05); the contents of 5-HT, DA and NE significantly increased (P<0.01, P<0.05). Conclusion The combination of Xiaoyao Kang'ai Jieyu Formula and paclitaxel can effectively relieve the depressive symptoms of breast cancer related depression.

Study on model of tree shrew induced by chronic corticosterone injection in anxious depression / 中国药理学通报

Aim To investigate the effects of chronic corticos-terone injection on anxiety and depression-like behavior of tree shrews, evaluate the predictability of drug and establish a novel animal model of anxious depression .Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group, model group and venlafaxine group .The anxious depres-sion model of tree shrew was established by chronic corticoster-one injection ( ih, 27 mg· kg-1 , 21 d) .The venlafaxine group received intragastric administration (6 mg· kg-1).Autonomous activity score, sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behav-ior of tree shrews .The expressions of CRH , ACTH and COR in the tree shrew plasma were determined by Elisa kit .The con-tents of monoamine neurotransmitters of tree shrews in the hippo-campus , amygdala and prefrontal cortex were detected by HPLC-ECD.Results Compared with the normal group , the autono-mous activity score , sugar water partial eclipse degree and the learning and memory ability significantly decreased (P<0.01), while the contents of CRH , ACTH and COR significantly in-creased ( P<0.05) , and the contents of 5-HT, NE and DA in the hippocampus , amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group, the learning and memory abilities of the tree shrews were improved , the lev-els of CRH and COR in plasma were significantly decreased ( P<0.05), and the contents of 5-HT, NE and DA were increased (P<0.05).Conclusions The tree shrews of anxious depres-sion have obvious HPA axis hyperactivity and monoamine neuro-transmitter disorder , and venlafaxine can reverse this phenome-non, indicating that the tree shrews model of anxious depression has drug predictability , which is a kind of novel animal model of anxious depression closer to human in clinic .

Anti-depressant effects of Jieyu Anshen granule in chronic unpredictable mild stress-treated rats after ischemic stroke / 中国药理学与毒理学杂志

OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule (JY) in chronic unpredictable mild stress (CUMS)-treated rats after ischemic stroke. METHODS A rat model of post-stroke depression(PSD)was developed by additional CUMS procedures after middle cere-bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg-1and 3 g·kg-1of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg-1)served as a reference drug.Behavioral tests including sucrose preference test, forced swim test and open-field test were performed to evaluate the antidepressant effects. Levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in rat brain were assayed. The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain. Serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were estimated as indices of hypothalamic-pituitary-adrenal (HPA) axis activity. Western blot analysis was used to evaluate hippo-campal expression of the 5-HT1A receptor (5-HT1AR) and brain-derived neurotrophic factor (BDNF). RESULTS PSD rats exhibited decreased sucrose consumption and motor activity, increased immobility time (P<0.01). JY treatment reversed the depressive behaviors in PSD rats (P<0.05, P<0.01). Treat-ment with JY resulted in significantly increased levels of NE, DA and 5-HT in the hippocampus and prefrontal cortex (P<0.05, P<0.01), and increased expression of 5- HT1AR and BDNF in the hippocampus(P<0.01). JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus andprefrontal cortex (P<0.05). Treatment with JY also resulted in significantly decreased ACTH and CORTin serum which had been increased (P<0.05). CONCLUSION These findings suggest that JY treat-ment could ameliorate PSD, and the effects are likely ascribed to inhibiting HPA axis hyperfunction andinflammatory, up-regulating the levels of neurotransmitters (NE, DA and 5-HT), and the expression ofhippocampal 5-HT1AR and BDNF.