Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppre...Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppression. Methods Forty-three SD rats were randomly, by using digits, divided into three groups： group A, B and C. Group A （n=10） was taken as a control group. Rats in group B （n=17） accepted intense swimming exercise for 150 min each time, 6 times each week for 8 weeks. Rats in group C （n=16） accepted EA intervention following each swimming since the second week of swimming exercise with the same duration and times as those in group B. The indices reflecting functional states of the HPA axis such as hypothalamic corticotropin releasing hormone （CRH）, plasma adrenocorticotropic hormone （ACTH）, corticosterone （CORT） etc. and changes in TE, serum γ-IFN, and IL-2 were determined. Results （1） Compared with group A, the values of ACTH and CORT in group B significantly increased （P〈0.01, P〈0.05）, but no significant differences were found in group C （both P〉0.05） though they were somewhat elevated. Compared with group A, CRH values increased by 85.14% in group B and decreased by 64.09% in group C, respectively, but both differences were without statistical significance （both P〉0.05）. Serum IL-2, γ-IFN and TE values in group B were significantly lower than those in group A（P〈0.05, P〈0.01 ）, among which γ-IFN decreased by 32.19%. The values of IL-2, γ-IFN and TE in group C tended to reduce but without significance, compared with group A. （2） Compared with group B, ACTH value in group C was very significantly lowered than that in group B （P〈0.01）, and CRH value was lower while CORT value was higher than those in group B but without significance （both P〉0.05）. The values of TE and γ-IFN in group C were significantly higher than those in group B （P〈0.01, P〈0.05）. Conclusion （1） Long-term of intense exercise induces accentuation of functions of the HPA axis and sustained high level of CORT, resulting in neuroendocrine disturbance and inhibition of immune functions. （2） EA provides favorable modulation on long-term of intense exercise-induced lowering of immune function and on the HPA axis.展开更多
The present study was designed to investigate the possible role ofHPA （hypothalamic-pituitary-adrenal） axis in neuropathic pain in streptozotocin induced diabetic rats. Wistar albino rats of either sex weighing 180-...The present study was designed to investigate the possible role ofHPA （hypothalamic-pituitary-adrenal） axis in neuropathic pain in streptozotocin induced diabetic rats. Wistar albino rats of either sex weighing 180-220 g （n = 6） were employed. Diabetes was induced by administering STZ （streptozotocin） （45 mg/kg, i.p.） once. Neuropathy was induced by the ligation of sciatic nerve in diabetic animals. A glucocorticoid receptor antagonist： ketoconazole 175 mg/kg, p.o. and glucocorticoid receptor agonist： hydrocortisone 1 mg/kg, i.p. were given. Assessment of neuropathic pain was achieved using hot plate and hot immersion tests. Tissue biochemical： lipid peroxidation, NO and glutathione were estimated on 28th day spectrophotometrically. Plasma cortisol level was also estimated using HPLC （high performance liquid chromatography）. Sciatic nerve ligation to diabetic animals caused significant increase in nociceptive responses as hyperalgesia and allodynia, tissue lipid peroxidation and NO products, and decrease in GSH （glutathione） level, in comparison to SC （saline control）. Ketoconazole administration produced decreased pain responses as well as decrease in oxidative stress and inflammatory mediators. Administration of hydrocortisone resulted in suppression of HPA axis. The activation of HPA axis in diabetic animals resulted in significant pain response. This may be due to increased corticosterone level which in turn desensitizes HPA axis and decreased nociceptive response in diabetic animals observed.展开更多
Objective:To observe the effects of long-snake moxibustion on the hypothalamic-pituitary-adrenocortical(HPA)axis and hepatic 11β-hydroxy steroid dehydrogenase type 1(11β-HSD1)expression in rats with kidney yang defi...Objective:To observe the effects of long-snake moxibustion on the hypothalamic-pituitary-adrenocortical(HPA)axis and hepatic 11β-hydroxy steroid dehydrogenase type 1(11β-HSD1)expression in rats with kidney yang deficiency to provide a basis for later in-depth exploration of the action mechanism of longsnakemoxibustion on suchrats.Methods:Fifteen SPF-grade,male,SD rats were randomly divided into a blank control group,a model group,and a long-snake moxibustion treatment group,with five rats in each group.Hydrocortisone powder(30 mg/kg)was administered by gavage at a volume of 10 mL/kg to prepare the rat model of kidney yang deficiency.After successful modeling,the rats in the long-snake moxibustion treatment group underwent long-snake moxibustion treatment every other day along the governor vessel from Dazhui(GV14)to Shenshu(BL23),for a period of 14 days.The remaining two groups were secured in the same way as the long-snake moxibustion treatment group,although they did not receive any treatment.The body weight,rectal temperature,and spontaneous activity count of the rats,as well as serum levels of corticotropin releasing hormone(CRH)and corticosterone(CORT)were detected by ELISA before modeling,after modeling,and after treatment.The amount of 11β-HSD1 protein in rat liver was determined by immunohistochemistry and Western blot analysis.Results:Compared with the rats in the blank control group,those in the model group exhibited a significant decrease in the trend of body weight growth and in rectal temperature(P<0.05),as well as a slight yet non-significant decrease in spontaneous activity count(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in rectal temperature(P<0.05)and in spontaneous activity count(P<0.05).Moreover,after 14 days of treatment,compared with the rats in the blank,the rats in the model group exhibited a significant decrease in serum cORT content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant decrease in serum CRH content(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in serum CRH content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant increase in serum CORT content(P>0.05).Conclusion:Long-snake moxibustion can increase the rectal temperature and spontaneous activity count of rats with kidney yang deficiency,improve the function of the HPA axis,and increase the expression of 11β-HSD1 in the liver.展开更多
Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats. Hyperactivity of the hypothalamic-pituitary-adrenal （HPA）...Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats. Hyperactivity of the hypothalamic-pituitary-adrenal （HPA） axis is one of the most consistent biological findings in anxiety- and depression-related disorders. The HPA axis is reported to be susceptible to developmental reprogramming. The present study focused on HPA reactivity in postnatal day （PND） 80 male rats exposed perinatally to environmental-dose BPA. When female breeders were orally administered 2 μg/（kg.day） BPA from gestation day 10 to lactation day 7, their offspring （PND 80 BPA-exposed rats） showed obvious anxiety/depression-like behaviors. Notably, significant increase in serum corticosterone and adrenocorticotropin, and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor. Additionally, the level of glucocorticoid receptor mRNA in the hippocampus, but not the hypothalamus, was decreased in BPA-exposed rats. The levels of hippocampal mineralocorticoid receptor mRNA, neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats. In addition, the testosterone level was in BPA-exposed rats. The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.展开更多
Anxiety disorder is a common and serious mental disorder.At present,the pathogenesis of anxiety disorder includes hypothalamus-pituitary-adrenal(HPA)axis,neuroimmune,and brain-gut axis disorders,among others.This pape...Anxiety disorder is a common and serious mental disorder.At present,the pathogenesis of anxiety disorder includes hypothalamus-pituitary-adrenal(HPA)axis,neuroimmune,and brain-gut axis disorders,among others.This paper discusses the correlation between anx-iety disorder and the hypothalamus-pituitary-endocrine axis and finds that immune inflammation can be used as a“bridge”between the hypothalamus-pituitary-endocrine axis and anxiety disorder.展开更多
Functional pain syndromes are very common diseases that negatively impact the quality of life of patients with important socio-economic repercussions. The clinical alterations associated with these pathologies are mul...Functional pain syndromes are very common diseases that negatively impact the quality of life of patients with important socio-economic repercussions. The clinical alterations associated with these pathologies are multiple and have a complex psycho-organic character that moves along the micorobiome-gut-brain-axis. For the present study, 45 patients of both sexes (19 male, 26 female) aged 30 - 59 years were enrolled because of a diagnosis of Functional pain syndromes (FPS) that lasted for more than 6 months. All patients underwent pre-treatment clinical assessments (T0) for anxiety disorder, multidimensional assessment of pain, monitoring of baseline values of Alpha-Theta cerebral rhythm in occipital region and monitoring of salivary cortisol levels. All the patients underwent a clinical treatment combined with central neuromodulation with neurofeedback—Alpha Theta increase protocols (once a week for three months), administration of multispecies probiotic (one dose per day for 3 months) and clinical psychological interviews (once a week for three months). At the end of treatment (T1), patients were re-evaluated. Results show statistically relevant improvements of each feature considered: the Relief from Pain provided by the medication increases on average from 36.6% to 87.3%, the salivary Cortisol level at 11 pm decreases from 6.4 ng/ml to a physiological value of 1.2 ng/ml, and the anxiety rating score is reduced from 28 to 12. Moreover, the 23.9% increase in α-θ relative power shows the positive outcome of the brain autoregulation. This study highlights that the combined approach of Neurofeedback with drugs and multispecies probiotic results in great improvements in the patients’ life.展开更多
The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adapt...The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.展开更多
There is no agreement on the etiology of chronic fatigue syndrome (CFS), and the main theories (behavioural and viral/immune) do not satisfactorily explain the condition. A growing body of evidence suggests that CFS m...There is no agreement on the etiology of chronic fatigue syndrome (CFS), and the main theories (behavioural and viral/immune) do not satisfactorily explain the condition. A growing body of evidence suggests that CFS may be caused by a dysfunction of the stress system—and the hypothalamic-pituitary-adrenal (HPA) axis in particular—as a result of chronic stress. CFS shares many similarities to occupational burnout, including similar symptoms, physiological abnormalities and triggers. After a brief review of the science of stress, burnout, central fatigue and CFS, I propose a model of CFS based on a state of persistent burnout that remains after the initial stressors have been removed. This persistence may be due to a combination of a dysregulation of the HPA axis, and behavioural factors. A novel treatment approach based on self-efficacy and positive goals is proposed.展开更多
Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of...Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine.Methods:10 C57BL/6J mice were used as blank group,and 20 ApoE-/-mice were randomly divided into AS group and AS+CUMS group.After one week of adaptive feeding,except for the blank group,the other two groups were fed with high fat diet.Meanwhile,the AS+CUMS group was given chronic unpredictable mild stress.The model was evaluated after 16 weeks of modeling.During the experiment,the body weight,food intake,excitability,hair color and other general morphology of mice in each group were observed and recorded.Behavioral indexes(Sucrose preference tests and Open Field test)were detected in each group.The levels of 5-hydroxytryptamine(5-HT)and hypothalamic-pituitary-adrenal(HPA)axis hormones,including adrenocorticotropin(ACTH)and corticosterone(CORT),were detected by ELISA.Serum lipid levels,including total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),were detected by ELISA.HE staining was used to observe the pathological condition of aorta.Results:Compared with blank group,the excitability and food intake of AS+CUMS group were significantly decreased.There were no significant differences in sugar water consumption and activity capacity of mice in AS group,while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased(P<0.01).The serum 5-HT levels in AS group and AS+CUMS group were decreased,and the levels of ACTH and CORT in AS+CUMS group were significantly decreased(P<0.01),and the levels of ACTH and CORT in AS+CUMS group were significantly increased(P<0.01).The serum TC,TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased(P<0.01),while the HDL-C level of mice in both groups was significantly decreased(P<0.01).HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier.Conclusion:High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.展开更多
Personality Disorders(PDs)and Anxiety Disorders(ADs)are common mental disorders.PDs are often more or less related to anxiety and ADs are affected by Personality Functioning(PF).To clarify the pathology of both ADs an...Personality Disorders(PDs)and Anxiety Disorders(ADs)are common mental disorders.PDs are often more or less related to anxiety and ADs are affected by Personality Functioning(PF).To clarify the pathology of both ADs and PDs,along with their similarities and differences,the literature review by paired keywords search on NCBI PubMed and subsequent analysis are used.The findings support that abnormal stressors can damage the Hypothalamus-Pituitary-Adrenal(HPA)axis time by time throughout life through the epigenetic pathway,lowering down the ability of the stress system to deal with stressors.Biological basis,like the genetic issue,for PDs,is important but after-born experience also matters a lot.Adjoint stressful long-term memory may largely affect normal personality formation,contributing to some kinds of PDs.It seems that early exposure to these stressors influences PDs more,compared to ADs.More researches are needed to explore the effect on ADs from later life stress.This study partially explained the process of ADs and PDs,linked them by abnormal stressors,and emphasized the importance of focusing on the effect of stressful long-term memory formation,which is psychological,and the HPA axis disability,which is biological,on patients having these diseases,reminds psychiatrist to treat disease at the source,to lower down the potential risk of getting PDs in patients who are diagnosed with ADs,to prevent arouse of ADs in patients who are diagnosed with PDs and to combine biological treatment with psychological therapies.展开更多
The “National Institutes of Health” genetically heterogeneous (NIH-HS) rat stock was created in the 1980s through an eight-way cross of as much as possible separate inbred rat strains (i.e. the MR/N, WN/N, WKY/N, M5...The “National Institutes of Health” genetically heterogeneous (NIH-HS) rat stock was created in the 1980s through an eight-way cross of as much as possible separate inbred rat strains (i.e. the MR/N, WN/N, WKY/N, M520/N, F344/N, ACI/N, BN/SsN and BUF/N strains) which were readily available at that time. Hansen and Spuhler [1] developed a more naturalistic, genetically heterogeneous rat stock with the aim of optimizing the distribution of genotypic frequencies and recombination and under the hypothesis that the NIH-HS stock could yield a broad-range distribution of responses (broader than commonly used laboratory rat strains) to experimental conditions, and thus serve as a base population for selection studies. Along the last decade, in a series of studies we have phenotypically characterized the NIH-HS rat stock (a colony exists at our laboratory since 2004) for their anxiety/fearfulness profiles (using a battery of both unconditioned and conditioned tests/tasks), as well as regarding their stress-induced hormonal responses, coping style under inescapable stress and spatial learning ability. We have also compared the phenotypic profiles of NIH-HS rats with those of the low anxious RHA-I and the high anxious RLA-I rat strains. The NIH-HS rat stock is, as a population, a rather anxious type of rat, with predominantly reactive/passive coping style in unlearned and learned anxiety/fear tests, and elevated stress hormone responses (as well as enhanced “depressive” symptoms in the forced swimming test). Genetic studies currently under way have thus far revealed that the genetically heterogeneous NIH-HS rat stock constitutes a unique tool for fine mapping of QTL (for multiple behavioural and biological complex traits) to megabase resolution levels, thus enabling candidate gene identification. We give some examples of this in the present paper, while also highlighting that microarray gene expression studies reveal that HPA-axis- and prolactin-related genes (among others) in the amygdala appear to be related with (or associated to) the coping style and anxiety/fearfulness responses of NIH-HS rats.展开更多
Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesi...Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.展开更多
Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown th...Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.展开更多
Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment,leading to changes in the regulation of multiple ...Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment,leading to changes in the regulation of multiple organ systems.This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term deter-minants that these epigenetic changes may have on future illness.We retrospectively ana-lysed the effect of exposure to adverse childhood experiences(ACEs,specifically those relating to childhood maltreatment)between the ages of 0 and 16years on the human epi-genome,as well as possible clinical associations.After meeting inclusion and exclusion crite-ria,36 articles were included in this systematic review.Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation.Of the remaining 28 studies,nine were genome-wide association studies,whereas the rest were candidate gene studies,mainly studying effects on neuroendocrine,serotoninergic and immunoregulatory systems.Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r=0.291(P<0.0001),and meta-analysis of two epigenome-wide association studies(EWASs)identified 44 differen-tially methylated CpG sites.In conclusion,childhood maltreatment may mediate epigenetic mechanisms through DNA methylation,thereby affecting physiological responses and con-ferring a predisposition to an increased risk for psychopathology and forensic repercussions.Similar evidence for somatic illnesses is not yet available.展开更多
It is commonly known that psychological stress affects immunity through the nervous system,but the specific stress networks between brain and peripheral leukocytes,or their relationship with disease initiation or prog...It is commonly known that psychological stress affects immunity through the nervous system,but the specific stress networks between brain and peripheral leukocytes,or their relationship with disease initiation or progression have yet to been delineated.A recent study by Poller and his colleagues1 propose an innovative perspective that distinct brain circuits rapidly manipulate a large-scale whole-body re-distribution of leukocytes(neutrophils,monocytes,lymphocytes)during psychological stress.展开更多
基金Supported by Guangdong Natural Science Foundation Project: 050042740
文摘Objective To observe modulatory effects of electroacupuncture （EA） on hypothalamus-pituitary adrenal （HPA） axis, thymus-exponent （TE）, γ-IFN and interleukin-2 （IL-2） in rats with exercise-induced immunosuppression. Methods Forty-three SD rats were randomly, by using digits, divided into three groups： group A, B and C. Group A （n=10） was taken as a control group. Rats in group B （n=17） accepted intense swimming exercise for 150 min each time, 6 times each week for 8 weeks. Rats in group C （n=16） accepted EA intervention following each swimming since the second week of swimming exercise with the same duration and times as those in group B. The indices reflecting functional states of the HPA axis such as hypothalamic corticotropin releasing hormone （CRH）, plasma adrenocorticotropic hormone （ACTH）, corticosterone （CORT） etc. and changes in TE, serum γ-IFN, and IL-2 were determined. Results （1） Compared with group A, the values of ACTH and CORT in group B significantly increased （P〈0.01, P〈0.05）, but no significant differences were found in group C （both P〉0.05） though they were somewhat elevated. Compared with group A, CRH values increased by 85.14% in group B and decreased by 64.09% in group C, respectively, but both differences were without statistical significance （both P〉0.05）. Serum IL-2, γ-IFN and TE values in group B were significantly lower than those in group A（P〈0.05, P〈0.01 ）, among which γ-IFN decreased by 32.19%. The values of IL-2, γ-IFN and TE in group C tended to reduce but without significance, compared with group A. （2） Compared with group B, ACTH value in group C was very significantly lowered than that in group B （P〈0.01）, and CRH value was lower while CORT value was higher than those in group B but without significance （both P〉0.05）. The values of TE and γ-IFN in group C were significantly higher than those in group B （P〈0.01, P〈0.05）. Conclusion （1） Long-term of intense exercise induces accentuation of functions of the HPA axis and sustained high level of CORT, resulting in neuroendocrine disturbance and inhibition of immune functions. （2） EA provides favorable modulation on long-term of intense exercise-induced lowering of immune function and on the HPA axis.
文摘The present study was designed to investigate the possible role ofHPA （hypothalamic-pituitary-adrenal） axis in neuropathic pain in streptozotocin induced diabetic rats. Wistar albino rats of either sex weighing 180-220 g （n = 6） were employed. Diabetes was induced by administering STZ （streptozotocin） （45 mg/kg, i.p.） once. Neuropathy was induced by the ligation of sciatic nerve in diabetic animals. A glucocorticoid receptor antagonist： ketoconazole 175 mg/kg, p.o. and glucocorticoid receptor agonist： hydrocortisone 1 mg/kg, i.p. were given. Assessment of neuropathic pain was achieved using hot plate and hot immersion tests. Tissue biochemical： lipid peroxidation, NO and glutathione were estimated on 28th day spectrophotometrically. Plasma cortisol level was also estimated using HPLC （high performance liquid chromatography）. Sciatic nerve ligation to diabetic animals caused significant increase in nociceptive responses as hyperalgesia and allodynia, tissue lipid peroxidation and NO products, and decrease in GSH （glutathione） level, in comparison to SC （saline control）. Ketoconazole administration produced decreased pain responses as well as decrease in oxidative stress and inflammatory mediators. Administration of hydrocortisone resulted in suppression of HPA axis. The activation of HPA axis in diabetic animals resulted in significant pain response. This may be due to increased corticosterone level which in turn desensitizes HPA axis and decreased nociceptive response in diabetic animals observed.
基金Supported by National Natural Science Foundation of China:81960900。
文摘Objective:To observe the effects of long-snake moxibustion on the hypothalamic-pituitary-adrenocortical(HPA)axis and hepatic 11β-hydroxy steroid dehydrogenase type 1(11β-HSD1)expression in rats with kidney yang deficiency to provide a basis for later in-depth exploration of the action mechanism of longsnakemoxibustion on suchrats.Methods:Fifteen SPF-grade,male,SD rats were randomly divided into a blank control group,a model group,and a long-snake moxibustion treatment group,with five rats in each group.Hydrocortisone powder(30 mg/kg)was administered by gavage at a volume of 10 mL/kg to prepare the rat model of kidney yang deficiency.After successful modeling,the rats in the long-snake moxibustion treatment group underwent long-snake moxibustion treatment every other day along the governor vessel from Dazhui(GV14)to Shenshu(BL23),for a period of 14 days.The remaining two groups were secured in the same way as the long-snake moxibustion treatment group,although they did not receive any treatment.The body weight,rectal temperature,and spontaneous activity count of the rats,as well as serum levels of corticotropin releasing hormone(CRH)and corticosterone(CORT)were detected by ELISA before modeling,after modeling,and after treatment.The amount of 11β-HSD1 protein in rat liver was determined by immunohistochemistry and Western blot analysis.Results:Compared with the rats in the blank control group,those in the model group exhibited a significant decrease in the trend of body weight growth and in rectal temperature(P<0.05),as well as a slight yet non-significant decrease in spontaneous activity count(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in rectal temperature(P<0.05)and in spontaneous activity count(P<0.05).Moreover,after 14 days of treatment,compared with the rats in the blank,the rats in the model group exhibited a significant decrease in serum cORT content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant decrease in serum CRH content(P>0.05);compared with the rats in the model group,the rats in the treatment group exhibited a significant increase in serum CRH content(P<0.05)and in the expression of 11β-HSD1 in the liver(P<0.05),as well as a slight yet non-significant increase in serum CORT content(P>0.05).Conclusion:Long-snake moxibustion can increase the rectal temperature and spontaneous activity count of rats with kidney yang deficiency,improve the function of the HPA axis,and increase the expression of 11β-HSD1 in the liver.
基金supported by China Postdoctoral Science Foundation(2013M540456)Jiangsu Planned Projects for Postdoctoral Research Funds(1301065B)+3 种基金Grants for 973(2014CB943303)NSFC(810710273117144081000482)
文摘Accumulating studies have proved that perinatal exposure to environmental dose causes long-term potentiation in anxiety/depression-related behaviors in rats. Hyperactivity of the hypothalamic-pituitary-adrenal （HPA） axis is one of the most consistent biological findings in anxiety- and depression-related disorders. The HPA axis is reported to be susceptible to developmental reprogramming. The present study focused on HPA reactivity in postnatal day （PND） 80 male rats exposed perinatally to environmental-dose BPA. When female breeders were orally administered 2 μg/（kg.day） BPA from gestation day 10 to lactation day 7, their offspring （PND 80 BPA-exposed rats） showed obvious anxiety/depression-like behaviors. Notably, significant increase in serum corticosterone and adrenocorticotropin, and corticotropin-releasing hormone mRNA were detected in BPA-exposed rats before or after the mild stressor. Additionally, the level of glucocorticoid receptor mRNA in the hippocampus, but not the hypothalamus, was decreased in BPA-exposed rats. The levels of hippocampal mineralocorticoid receptor mRNA, neuronal nitric oxide synthase and phosphorylated cAMP response element binding protein were increased in BPA-exposed rats. In addition, the testosterone level was in BPA-exposed rats. The results indicate that reprogramming-induced hyperactivity of the HPA axis is an important link between perinatal BPA exposure and persistent potentiation in anxiety and depression.
文摘Anxiety disorder is a common and serious mental disorder.At present,the pathogenesis of anxiety disorder includes hypothalamus-pituitary-adrenal(HPA)axis,neuroimmune,and brain-gut axis disorders,among others.This paper discusses the correlation between anx-iety disorder and the hypothalamus-pituitary-endocrine axis and finds that immune inflammation can be used as a“bridge”between the hypothalamus-pituitary-endocrine axis and anxiety disorder.
文摘Functional pain syndromes are very common diseases that negatively impact the quality of life of patients with important socio-economic repercussions. The clinical alterations associated with these pathologies are multiple and have a complex psycho-organic character that moves along the micorobiome-gut-brain-axis. For the present study, 45 patients of both sexes (19 male, 26 female) aged 30 - 59 years were enrolled because of a diagnosis of Functional pain syndromes (FPS) that lasted for more than 6 months. All patients underwent pre-treatment clinical assessments (T0) for anxiety disorder, multidimensional assessment of pain, monitoring of baseline values of Alpha-Theta cerebral rhythm in occipital region and monitoring of salivary cortisol levels. All the patients underwent a clinical treatment combined with central neuromodulation with neurofeedback—Alpha Theta increase protocols (once a week for three months), administration of multispecies probiotic (one dose per day for 3 months) and clinical psychological interviews (once a week for three months). At the end of treatment (T1), patients were re-evaluated. Results show statistically relevant improvements of each feature considered: the Relief from Pain provided by the medication increases on average from 36.6% to 87.3%, the salivary Cortisol level at 11 pm decreases from 6.4 ng/ml to a physiological value of 1.2 ng/ml, and the anxiety rating score is reduced from 28 to 12. Moreover, the 23.9% increase in α-θ relative power shows the positive outcome of the brain autoregulation. This study highlights that the combined approach of Neurofeedback with drugs and multispecies probiotic results in great improvements in the patients’ life.
基金Foundation items： The preparation of this review was partially supported by a grant from the National Institute of Mental Health （5R01 MH097718-02）, U.S.A.
文摘The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.
文摘There is no agreement on the etiology of chronic fatigue syndrome (CFS), and the main theories (behavioural and viral/immune) do not satisfactorily explain the condition. A growing body of evidence suggests that CFS may be caused by a dysfunction of the stress system—and the hypothalamic-pituitary-adrenal (HPA) axis in particular—as a result of chronic stress. CFS shares many similarities to occupational burnout, including similar symptoms, physiological abnormalities and triggers. After a brief review of the science of stress, burnout, central fatigue and CFS, I propose a model of CFS based on a state of persistent burnout that remains after the initial stressors have been removed. This persistence may be due to a combination of a dysregulation of the HPA axis, and behavioural factors. A novel treatment approach based on self-efficacy and positive goals is proposed.
基金Fund Project:National Natural Science Foundation of China(No.81874415)Liaoning Province Traditional Chinese Medicine Clinical Key Discipline(Specialty)Service Capacity Building Project(No.LNZYXZK.201908)。
文摘Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine.Methods:10 C57BL/6J mice were used as blank group,and 20 ApoE-/-mice were randomly divided into AS group and AS+CUMS group.After one week of adaptive feeding,except for the blank group,the other two groups were fed with high fat diet.Meanwhile,the AS+CUMS group was given chronic unpredictable mild stress.The model was evaluated after 16 weeks of modeling.During the experiment,the body weight,food intake,excitability,hair color and other general morphology of mice in each group were observed and recorded.Behavioral indexes(Sucrose preference tests and Open Field test)were detected in each group.The levels of 5-hydroxytryptamine(5-HT)and hypothalamic-pituitary-adrenal(HPA)axis hormones,including adrenocorticotropin(ACTH)and corticosterone(CORT),were detected by ELISA.Serum lipid levels,including total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),were detected by ELISA.HE staining was used to observe the pathological condition of aorta.Results:Compared with blank group,the excitability and food intake of AS+CUMS group were significantly decreased.There were no significant differences in sugar water consumption and activity capacity of mice in AS group,while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased(P<0.01).The serum 5-HT levels in AS group and AS+CUMS group were decreased,and the levels of ACTH and CORT in AS+CUMS group were significantly decreased(P<0.01),and the levels of ACTH and CORT in AS+CUMS group were significantly increased(P<0.01).The serum TC,TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased(P<0.01),while the HDL-C level of mice in both groups was significantly decreased(P<0.01).HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier.Conclusion:High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.
文摘Personality Disorders(PDs)and Anxiety Disorders(ADs)are common mental disorders.PDs are often more or less related to anxiety and ADs are affected by Personality Functioning(PF).To clarify the pathology of both ADs and PDs,along with their similarities and differences,the literature review by paired keywords search on NCBI PubMed and subsequent analysis are used.The findings support that abnormal stressors can damage the Hypothalamus-Pituitary-Adrenal(HPA)axis time by time throughout life through the epigenetic pathway,lowering down the ability of the stress system to deal with stressors.Biological basis,like the genetic issue,for PDs,is important but after-born experience also matters a lot.Adjoint stressful long-term memory may largely affect normal personality formation,contributing to some kinds of PDs.It seems that early exposure to these stressors influences PDs more,compared to ADs.More researches are needed to explore the effect on ADs from later life stress.This study partially explained the process of ADs and PDs,linked them by abnormal stressors,and emphasized the importance of focusing on the effect of stressful long-term memory formation,which is psychological,and the HPA axis disability,which is biological,on patients having these diseases,reminds psychiatrist to treat disease at the source,to lower down the potential risk of getting PDs in patients who are diagnosed with ADs,to prevent arouse of ADs in patients who are diagnosed with PDs and to combine biological treatment with psychological therapies.
基金grants for the MICINN (PSI2009-10532) “Fundació La Maratò TV3” (ref. 092630/31) 2009SGR-0051 and the European pro- ject/consortium “EURATRANS” (grant agreement HEALTH-F4- 2010-241504)
文摘The “National Institutes of Health” genetically heterogeneous (NIH-HS) rat stock was created in the 1980s through an eight-way cross of as much as possible separate inbred rat strains (i.e. the MR/N, WN/N, WKY/N, M520/N, F344/N, ACI/N, BN/SsN and BUF/N strains) which were readily available at that time. Hansen and Spuhler [1] developed a more naturalistic, genetically heterogeneous rat stock with the aim of optimizing the distribution of genotypic frequencies and recombination and under the hypothesis that the NIH-HS stock could yield a broad-range distribution of responses (broader than commonly used laboratory rat strains) to experimental conditions, and thus serve as a base population for selection studies. Along the last decade, in a series of studies we have phenotypically characterized the NIH-HS rat stock (a colony exists at our laboratory since 2004) for their anxiety/fearfulness profiles (using a battery of both unconditioned and conditioned tests/tasks), as well as regarding their stress-induced hormonal responses, coping style under inescapable stress and spatial learning ability. We have also compared the phenotypic profiles of NIH-HS rats with those of the low anxious RHA-I and the high anxious RLA-I rat strains. The NIH-HS rat stock is, as a population, a rather anxious type of rat, with predominantly reactive/passive coping style in unlearned and learned anxiety/fear tests, and elevated stress hormone responses (as well as enhanced “depressive” symptoms in the forced swimming test). Genetic studies currently under way have thus far revealed that the genetically heterogeneous NIH-HS rat stock constitutes a unique tool for fine mapping of QTL (for multiple behavioural and biological complex traits) to megabase resolution levels, thus enabling candidate gene identification. We give some examples of this in the present paper, while also highlighting that microarray gene expression studies reveal that HPA-axis- and prolactin-related genes (among others) in the amygdala appear to be related with (or associated to) the coping style and anxiety/fearfulness responses of NIH-HS rats.
基金funded by the Italian Ministry of Education,University and Research(PRIN GEN2PHEN)
文摘Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.
基金Yunnan Provincial Department of Science and Technology Project(202101AY070001-224).
文摘Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.
文摘Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment,leading to changes in the regulation of multiple organ systems.This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term deter-minants that these epigenetic changes may have on future illness.We retrospectively ana-lysed the effect of exposure to adverse childhood experiences(ACEs,specifically those relating to childhood maltreatment)between the ages of 0 and 16years on the human epi-genome,as well as possible clinical associations.After meeting inclusion and exclusion crite-ria,36 articles were included in this systematic review.Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation.Of the remaining 28 studies,nine were genome-wide association studies,whereas the rest were candidate gene studies,mainly studying effects on neuroendocrine,serotoninergic and immunoregulatory systems.Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r=0.291(P<0.0001),and meta-analysis of two epigenome-wide association studies(EWASs)identified 44 differen-tially methylated CpG sites.In conclusion,childhood maltreatment may mediate epigenetic mechanisms through DNA methylation,thereby affecting physiological responses and con-ferring a predisposition to an increased risk for psychopathology and forensic repercussions.Similar evidence for somatic illnesses is not yet available.
基金This work was supported by the National Natural Science Foundation of China(No.82125038,82004231)Guangdong Basic and Applied Basic Research Fund(No.2020A1515110388,China)GDUPS(2019,China).
文摘It is commonly known that psychological stress affects immunity through the nervous system,but the specific stress networks between brain and peripheral leukocytes,or their relationship with disease initiation or progression have yet to been delineated.A recent study by Poller and his colleagues1 propose an innovative perspective that distinct brain circuits rapidly manipulate a large-scale whole-body re-distribution of leukocytes(neutrophils,monocytes,lymphocytes)during psychological stress.
