Protective effect of LW-AFC against fear sensitization induced by traumatic stress / 军事医学

Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside(LW-AFC)against fear sensitization induced by traumatic stress.Methods Mice were divided into naive,control,stressed and LW-AFC administration groups.The LW-AFC treated group received LW-AFC(1.6 g/kg daily)via oral gavage for two weeks following exposure to traumatic stress.The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated,including behavior in novel environments,social interaction,and observational fear tests.Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance,freezing time,and corner time,and comprehensively examined fear sensitization behaviors across the groups.Additionally,serum concentrations of adrenocorticotropic hormone,corticosterone,aldosterone,renin,angiotensin Ⅱ,and aldosterone were measured using ELISA.Results Compared to the control group,stressed mice exhibited significantly reduced travel distance(P<0.0001)and increased freezing time(P<0.0001)in the new context test.Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test(P<0.0001).In the social interaction test,stressed mice demonstrated significantly reduced travel distance(P<0.0001),increased freezing time(P<0.0001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).In the observational fear test,stressed mice showed significantly reduced travel distance(P<0.05),increased freezing time(P<0.001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).Compared to the stressed group,mice in the LW-AFC treated group displayed trends toward improvement in travel distance,freezing time,corner time,and integrated Z-scores in the new context tests,albeit without statistical significance.In the social interaction test,the LW-AFC treated group exhibited a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.05).In the observational fear test,the LW-AFC treated group showed a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.01).Compared to the naive group,control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test.Although there were no significant differences between stressed and control groups,renin and aldosterone levels significantly increased between stressed and naive groups(P<0.05,P<0.05).Following LW-AFC treatment,serum renin levels showed no significant change,while aldosterone levels significantly decreased(P<0.05).Conclusion Stressed mice exhibited significant fear sensitization behavior in new context,social interaction,and observational fear tests,possibly associated with partial activation of the renin-angiotensin-aldosterone system(RAAS)system.LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test,potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.

Mechanism of Electroacupuncture in Functional Dyspepsia Rats Based on Hypothalamic-Pituitary-Adrenal Axis / 世界科学技术-中医药现代化

Objective We aimed to explore the therapeutic mechanism of electroacupuncture at Yintang(EX-HN3),Neiguan(PC6)and Zusanli(ST36)on the Hypothalamic-Pituitary-Adrenal axis(HPA)of functional dyspepsia(FD)rats.Methods Forty SD rats were randomly divided into blank group,model group and EA group.The FD model was replicated by tail clamping,irregular diet,and filling the stomach with ice of Saline Solution.After modeling,the EA group received acupuncture treatment for 1 time day,30 minutes time,for 14 days.Recording the general state of the rat.Detection of locomotion and catatonia in rats by open field test.HE staining to observe the morphology and inflammation of gastric mucosa in rats.PCR detection of mRNA expression of 5-hydroxytryptamine3 receptor and corticotropin-releasing hormone in rat hypothalamus.Detection of corticotropin-releasing hormone receptor-2 and NOD-like receptor protein 6 inflammasome protein expression in rat duodenum by Western blotting.Alcian blue staining was used to detect the expression of rat duodenum goblet cells.Results Compared with the blank group,the general state,distance,speed,duodenum CRHR2 and NLRP6 proteins in the model group were significantly decreased(P<0.05),the hypothalamic 5-HT3R and CRH mRNA were significantly increased(P<0.05).Compared with the model group,the general state,distance,speed,expression of CRHR2,NLRP6 protein and goblet cells in the duodenum of rats in the EA group were significantly increased(P<0.05),the 5-HT3R and CRH mRNA in the hypothalamus were significantly decreased(P<0.05).In the model group,the connective tissue of the gastric mucosa was loosely arranged,the submucosa had mild edema,and there were some lymphocytes.The connective tissue of the gastric mucosa of the rats in the blank group and the electroacupuncture group was closely arranged,and there was no obvious proliferation of interstitial cells and no inflammatory cells.Conclusion EA can increase the expression of CRHR2,NLRP6 protein and goblet cells in the duodenum,and inhibit the expression of 5-HT3R and CRH in the hypothalamus.EA can improve gastrointestinal motility and locomotion,relieve anxiety,repair the mucosal barrier of the defective intestine,and restore the function of the Hypothalamic-Pituitary-Adrenal axis.

Risk factors of depression and anxiety in epilepsy patients and their relationship with quality of life / 实用医学杂志

Objective To explore the risk factors of depression and anxiety in adult patients with epilepsy and their relationship with quality of life.Methods From May 2022 to January 2023,patients diagnosed with epilepsy(aged≥18 years)in the department of neurology of our hospital were collected.General demographic data and disease-related information were recorded.Quality of life,depression and anxiety scales were measured in all patients.SPSS26.0 software was used for multiple linear regression analysis,multiple ordered Logistic regression analysis,rank sum test,Pearson correlation analysis,etc.Results Among the 111 patients,49.5%had depression and 43.2%had anxiety.Depression score and anxiety score were correlated with attack type,attack frequency,quality of life and right temporal lobe,and there was a significant negative correlation between life quality score and anxiety and depression score(P<0.01).Seizure frequency,seizure type and right temporal lobe were common risk factors for depression and anxiety in patients with epilepsy(P<0.05).Conclusion Epileptic depression and anxiety were affected by seizure frequency and seizure type,and this bad mood further affected the quality of life of patients.No clear link has been found between the lateralization of seizures and the presence of depression and anxiety states,and further research is needed.

Establishment and Evaluation of Mouse Model of Pregnancy Pain-depression Comorbidity Induced by Chronic Unpredictable Stress, Complete Freund's Adjuvant and Formalin / 实验动物与比较医学

Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress (CUS), complete Freund's adjuvant (CFA), and formalin, and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity.Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group (no intervention before pregnancy) and a CUS model group (CUS intervention before pregnancy) based on sucrose preference test (SPT) data. After completing the CUS treatment, female and male mice were paired and mated. Pain was induced by injecting 50% CFA and 5% formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity. The experiment was divided into 8 subgroups: control-blank group, CUS-blank group, control-CFA group, CUS-CFA group, control-formalin group, CUS-formalin group, control-CFA+formalin group, and CUS-CFA+formalin group, with 10 mice in each group. The mice in each group were subject to behavioral tests, including the SPT, forced swimming test, tail suspension test, and open field test before and after CUS intervention, during pregnancy, and after delivery. Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests. Mice were then euthanized. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in hippocampus, as well as cortisol and adrenocorticotropic hormone (ACTH) in serum, were detected by enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the control-blank group, the CUS-blank group showed a significant depression-like behavior with reduced pain threshold (P<0.001). The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection (P<0.01). Compared with the control-blank and control-formalin groups, the pain threshold was significantly lower in the CUS-formalin group (P<0.01), with a sequential decrease among the three. Compared with the control-blank and control-CFA groups, the pain threshold was significantly lower in the CUS-CFA group (P<0.001), with a sequential decrease among the three. Compared with the control-blank and control-CFA+formalin groups, the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower (P<0.001) and the thermal radiation tolerance time was shorter (P<0.01), both with sequential decreases among the three. Compared with the control-CFA+formalin and the CUS-blank groups, the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference (P<0.001), longer immobility time during the forced swimming test (P<0.001) and tail suspension test (P<0.001), reduced central exploration time in the open field test (P<0.001), reduced total exploration distance (P<0.001), and reduced percentage of distance traveled for central exploration (P<0.001). Compared with the control-CFA+formalin and CUS-blank groups, the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher (P<0.01), and the levels of IL-6 and TNF-α in the hippocampus were higher (P<0.05).Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity. The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal (HPA) axis.

Effect and mechanism investigation on improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata based on plasma metabolomics / 药学学报

Plasma nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata. Thirty-five ICR mice were randomly divided into the control group, the model group, the BB24 h (braising with black bean sauce for 24 hours) group, the BB32 h group, and the BB40 h group. Biochemical indices in blood plasma of mice were measured by collecting eye blood after modeling. Changes in plasma endogenous metabolites of mice from each group were determined by ultra-performance liquid chromatography-linear trap quadrupole-orbitrap XL (UPLC-LTQ-orbitrap XL), and differential metabolites were screened. The results of pharmacodynamic investigation showed that compared to the model group, the levels of estradiol increased obviously in the BB24 h (P < 0.05), and the levels of cortisol increased obviously in BB32 h (P < 0.05). The hormone level of mice with kidney deficiency was significantly improved after taking processed Polygonum multiflorum. A total of 70 differential endogenous metabolites in blood plasma of mice were identified from all treatment groups, which mainly involved glycerophospholipid meta-bolism, arachidonic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism. The study indicated that Polygoni Multiflori Radix Praeparata may play the role of tonifying liver and kidney by improving the disorder of hypothalamic-pituitary-adrenal axis and regulating lipid metabolism in mice. Correlation analysis on differential metabolites in blood plasma and the chemical constituents showed that stilbene glycosides and saccharides may be the key pharmacodynamic material basis. The present study provides a new reference and theoretical foundation for revealing the potential pharmacodynamic material basis and mechanism investigation on tonifying liver and kidney of Polygoni Multiflori Radix Praeparata. This study was carried out following the ethical guidelines and regulations for the use of laboratory animals of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and passed the animal experimental ethical review [No. SYXK (Jing) 2019-0003].

Regulating effects of Neiguan(PC6)and Gongsun(SP4)on hypothalamic-pituitary-adrenal axis in rats with functional dyspepsia / 针灸推拿医学（英文版）

Objective:To investigate the effects and the possible mechanisms of Neiguan(PC6)and Gongsun(SP4)on the hypothalamic-pituitary-adrenal(HPA)axis in rats with functional dyspepsia(FD),thus to provide a theoretical basis for the clinical application of the Eight Confluent Points.Methods:Forty specific-pathogen-free Sprague-Dawley rats were divided into a blank group,a model group,an electroacupuncture(EA)group,and a Western medicine group by the random number table method,with 10 rats in each group.Rats in the blank group did not receive modeling or intervention.Rats in the other three groups were subjected to the FD with mood disorder model using the compound etiology modeling method.After the successful modeling,rats in the model group did not receive any interventions,rats in the Western medicine group received deanxit and mosaprid intervention,and those in the EA group received EA intervention on the ipsilateral Neiguan(PC6)and Gongsun(SP4)for 21 d.The sugar-water consumption rate was measured before the experiment and before and after interventions to assess the emotional status.The gastric emptying rate was measured after interventions to assess the gastrointestinal dynamics.The expression levels of hypothalamic corticotropin-releasing hormone(CRH),pituitary adrenocorticotropic hormone(ACTH),and adrenal corticosterone(CORT)were measured by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the sugar-water consumption rate and the gastric emptying rate were decreased(P<0.01),and the hypothalamic CRH,pituitary ACTH,and adrenal CORT expression levels were increased(P<0.01)in the model group.Compared with the model group,the sugar-water consumption rate and the gastric emptying rate were significantly increased(P<0.01),while the expression levels of hypothalamic CRH,pituitary ACTH,and adrenal CORT were significantly decreased(P<0.01)in the EA group and the Western medicine group.The differences between the EA group and the Western medicine group were not statistically significant(P>0.05).Conclusion:The Eight Confluent Points Neiguan(PC6)and Gongsun(SP4)can improve the mood and gastrointestinal dynamics in FD rats,which may be achieved by down-regulating the hypothalamic CRH,pituitary ACTH,and adrenal CORT,as well as by correcting the HPA axis hyperfunction.

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.

Hypothalamic-Pituitary-Adrenal axis activity in SARS-CoV-2 infected noncritically ill hospitalized patients / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#This study determined the baseline hormonal levels of the hypothalamic-pituitary-adrenal axis and their associated factors in noncritically ill hospitalized patients with coronavirus disease 2019 (COVID-19).@*Methodology@#This cross-sectional observational study was carried out in 91 noncritical RT-PCR-confirmed COVID-19 patients (18-65 years) recruited consecutively from the COVID unit, of two tertiary care hospitals over a period of six months. After screening for exclusion criteria relevant history and physical examinations were done, and blood was drawn between 07:00 am to 09:00 am in a fasting state to measure serum cortisol and plasma adrenocorticotropic hormone (ACTH) by chemiluminescent microparticle immunoassay.@*Result@#Of 91 patients, 54, 26, and 11 had mild, moderate, and severe disease respectively. Median values of serum cortisol (p=0.057) and plasma ACTH (p=0.910) were statistically similar among the severity groups. Considering cortisol cut-off of 276 nmol/L (<10 μg/dL), the highest percent of adrenal insufficiency was present in severe (27.3%), followed by mild (25.9%) and least in moderate (3.8%) COVID-19 cases. Using the cortisol/ACTH ratio >15, only 6.6% had enough reserve.@*Conclusions@#The adrenocortical response was compromised in a significant percentage of noncritically ill hospitalized patients with COVID-19, which is unrelated to infection severity, with greater percentages present in severely infected cases.

Research progress on effects of intergenerational transmission on allergic disease susceptibility in offspring / 中国药理学通报

Allergic diseases are diseases caused by abnormal immune responses to antigens. Recently the prevalence of allergic diseases in children is on the rise, which has become one of the urgent public health problems to date. Recent clinical data and research show that the susceptibility of allergic diseases in offspring is inextricably associated with intergenerational transmission factors. Some unfavorable factors suffered by mothers before or during pregnancy may increase the allergic disease susceptibility in offspring. Therefore, it is of great significance to identify early risk factors (mother's generation) for the prevention of allergic diseases in children. At present, under the background of intergenerational transmission, some progress has been made in the research on the susceptibility of allergic diseases in offspring, and some researches have elucidated the potential molecular biological mechanisms. The current review summarizes the effects of maternal pregestational and prenatal unfavorable factors on the susceptibility of allergic diseases in offspring.

The effect of psychosocial stress on asthma in children and its mechanism / 国际儿科学杂志

With the development of the understanding of bronchial asthma(asthma for short) and the accumulation of diagnosis and treatment experience, people realize that asthma is a heterogeneous physical and mental disease.Psychosocial stress can increase the frequency of asthma attacks in children and increase the burden of family and society.Psychosocial stress from individual, family and other levels transduces signals in the brain, which are transmitted to downstream effectors, producing effectors such as adrenocorticosteroids, enhancing Th2 and Th17 cell responses, inhibiting Treg cell responses, and influencing specific asthma related genotypes.This paper reviews the mechanism of psychosocial stress on asthma, in order to better control and treat asthma and improve the quality of life of children with asthma.

Progress on correlation between intestinal flora and mental diseases / 中国药理学通报

The impact of intestinal flora on human and animal health and diseases has attracted much attention both at home and abroad in recent years. The intestinal flora constitutes the intestinal microecosystem and plays an important role in physiological activities such as nutrition, metabolism, growth and development, barrier protection, and immunity. In this article, the relationship between intestinal dysbiosis and psychiatric diseases has been reviewed from two aspects:metagenomic characterization of intestinal microflora diversity in neurological diseases and validation of the relationship between intestinal flora and psychiatric diseases by fecal bacteria transplantation in germ-free mice. In addition, the microbial-gut-brain axis theory has been proposed in recent years, which links the nerve-endocrine-immune system to form a two-way signaling pathway. Intestinal flora plays an important role in regulating the central nervous system by promoting neurotransmitter release, endocrine, and immunity. The system plays an important role. Changes in intestinal flora mainly affect the host's nervous system through vagus nerve pathways, endocrine pathways, immune pathways, etc, thereby triggering or aggravating depression, autism, Alzheimer's disease, schizophrenia, Parkinson's disease, etc. This article reviews the relationships between host-related neurological abnormalities, intestinal flora imbalance and mental diseases, and discusses the research methods, research progress, and mechanism of the correlation between intestinal flora imbalance and mental diseases to research progress on microbe-gut-brain axis.

Advances on mechanisms of hypothalamic-pituitary-adrenal axis in abnormal glucose metabolism induced by air pollution / 环境与职业医学

Recently, the adverse health effects of air pollution on human have attracted more and more attentions. Particulate matters (such as PM2.5 and PM10, with aerodynamic diameters ≤2.5 and ≤10 µm, respectively) and ozone are the major ambient pollutants in China. A large number of studies have shown that exposure to particulate matters or ozone induces metabolic abnormalities, such as type 2 diabetes. However, the underlying biological mechanisms are not clear. In this review, we introduced the epidemiological and toxicological research progress of the effects of air pollutants on hypothalamus-pituitary-adrenal (HPA) axis. Considering the critical role of HPA axis in stress response, the molecular mechanisms of HPA axis-mediated glucose metabolism in fat, liver, muscle, and other tissues were also summarized. By integrating relevant literature and references, we proposed that HPA axis may play an important role in the abnormal glucose metabolism caused by air pollution, providing a scientific basis for future studies on the intervention methods of adverse health effects induced by air pollution.

Ginkgo diterpene lactone improves depression-like behaviors and affects cytokine and neurotransmitter levels in a rat model of chronic unpredictable mild stress / 中华微生物学和免疫学杂志

Objective:To investigate the effects of Ginkgo diterpene lactone on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS) and its mechanism.Methods:Forty SD rats were randomly divided into five groups, which were control group, CUMS group, CUMS+ low-dose Ginkgo diterpene lactone group (1.5 mg·kg -1·d -1), CUMS+ medium-dose Ginkgo diterpene lactone group (3 mg·kg -1·d -1) and CUMS+ high-dose Ginkgo diterpene lactone group (6 mg·kg -1·d -1). CUMS rat model was established by continuous stress for six weeks, and the rats were given corresponding treatment in the last three weeks. Sucrose preference test was performed during the stress and drug administration, and behavior tests were performed after the stress and drug administration. After behavior tests, hippocampus, hypothalamus and serum samples were collected to detect inflammatory factors and neurotransmitter. Results:Chronic stress caused depression-like behaviors in rats, while continuous treatment with Ginkgo diterpene lactone could effectively improve sucrose preference, forced swimming immobility time and open field test scores in CUMS rats. It was found that Ginkgo diterpene lactone could significantly improve the decreased secretion of IL-1β and IFN-γ in plasma, and significantly increase the secretion of IL-10 and IL-4 caused by CUMS. In addition, CUMS caused hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis in rats, which manifested as increased secretion of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (COR). The negative feedback of HPA hypermodulated the release of neurotransmitters in the hippocampus, causing the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) in the brain of CUMS rats to decrease. However, Ginkgo diterpene lactone could significantly inhibit HPA axis hyperfunction and increase neurotransmitter levels in the brain.Conclusions:Ginkgo diterpene lactone can effectively improve the depression-like behaviors of CUMS rats through regulating the immune environment, inhibiting the HPA axis hyperfunction and increasing neurotransmitter release.

The impact of masticatory dysfunction caused by occlusal disharmony on cognitive function / 口腔疾病防治

@#As the world’s population ages, age-related cognitive decline and dementia are becoming important challenges for geriatric care. Despite the ongoing search for solutions to address cognitive decline, effective interventions have not yet been established. There is increasing evidence from clinical, epidemiological, and animal studies that masticatory dysfunction due to occlusal disharmony is a risk factor for cognitive decline and an increased incidence of dementia. The mechanisms may involve altered nutritional intake, decreased cerebral blood flow, chronic stress, and hippocampal morphological function. These findings suggest that maintaining and adequately restoring the entire masticatory system has a positive impact for the prevention of cognitive decline.

Colapso del inmunoprivilegio y estrés emocional en Alopecia Areata / Collapse of the immunoprivilege and emotional stress in alopecia areata

Resumen El folículo piloso es una estructura compleja que presenta diversas características morfológicas macroscópicas, microscópicas e inmunológicas especiales que permiten el adecuado funcionamiento de la misma, en algunasenfermedades estos mecanismos de regulación inmunológica se ven alteradose incluso exacerbados por factores como el estrés emocional. El objetivo de esta revisión es conocer los mecanismos inmunobiológicos específicos del folículo pilosoanalizando el papel que juegan diversos factores como la pérdida delinmunoprivilegio y el estrés emocional en el desarrollo de la alopecia areata.

Abstract The hair follicle is a complex structure that presents diverse morphologicaland immunological characteristics that allow the proper functioning of the unit.In some diseases as alopecia areata these mechanisms of immune regulation are disrupted by external factorssuch as emotional stress preventing the growth of the hair shaft. The objective of this review is to recognize the specific immunobiological mechanisms of the hair follicle, analyzing the role played by the loss of immunoprivilege and emotional stress in the development of alopecia areata.

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

Efectos del tratamiento antioxidante en la activación del eje hipotálamo-hipófiso-adrenal inducida por el consumo de dietas ricas en sacarosa / Effects of antioxidant treatment on the activation of the hipotalamo-hipofiso-adrenal axis induced by the consumption of sucrose rich diets

Introducción: dados los efectos pleiotrópicos de los glucocorticoides (GCs) sobre el metabolismo, los niveles excesivos y sostenidos de GCs circulantes tienen efectos deletéreos e incrementan la morbilidad y mortalidad cardiovascular. Objetivos: estudiar el efecto de la terapia antioxidante (con ácido lipoico o melatonina) sobre la hiperactivación del eje hipotálamo-hipófiso-adrenal (HHA) en animales alimentados con dieta rica en sacarosa (DRS). Materiales y métodos: se evaluó la actividad del eje HHA y se determinaron parámetros hormonales, de estrés oxidativo y de inflamación en la adenohipófisis de animales tratados con DRS durante tres semanas. Resultados: los animales del grupo DRS mostraron mayores niveles circulantes de hormona adrenocorticotropa (ACTH, por sus siglas en inglés) y corticosterona. En paralelo se detectó un aumento en la expresión del polipéptido precursor (proopiomelanocortina, POMC) y de ACTH en la adenohipófisis, donde también se observó un aumento de lipoperóxidos y proteínas nitradas en tirosina (daño oxidativo), un mayor número de macrófagos tisulares y un incremento en la producción de IL-1beta. El tratamiento antioxidante previno los cambios en estos parámetros. En particular la melatonina también normalizó la actividad del eje HHA y la expresión hipofisaria de POMC. Conclusiones: la sobrecarga metabólica inducida por la administración de DRS genera daño oxidativo e inflamación en la adenohipófisis. La activación de los macrófagos tisulares producida en consecuencia podría impactar sobre los corticotropos hipofisarios e inducir su hiperfunción. La melatonina podría utilizarse como herramienta terapéutica para normalizar la actividad del eje HHA en modelos de obesidad por dieta.

Introduction: given the pleiotropic effects of glucocorticoids (GCs) on metabolism, excessive and sustained levels of circulating GCs, have deleterious effects and increase cardiovascular morbidity and mortality. Objectives: to study the effect of antioxidant therapy on hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis in animals fed a sucrose-rich diet (SRD). Materials and methods: the activity of the HPA axis was evaluated and hormonal, oxidative stress and inflammation parameters were determined in the adenohypophysis of animals treated with SRD for trhee weeks. Results: animals from the SRD group showed higher circulating levels of adrenocorticotropic hormone (ACTH) and corticosterone. In parallel, an increase in the expression of the polypeptide precursors, POMC and ACTH were detected in the adenohypophysis. We also observed an increase in lipoperoxides and proteins nitrated in tyrosine (oxidative damage), a greater number of tissue macrophages and an increase in the production of IL-1beta. Antioxidant treatment prevented all these changes. In particular, melatonin also normalized the activity of the HPA axis and pituitary expression of POMC. Conclusions: the metabolic overload induced by the administration of SRD generates oxidative damage and inflammation in the adenohypophysis. Activation of tissue macrophages could affect, in turn, pituitary corticotrophs inducing their activation. Melatonin could be used as a therapeutic tool to normalize the activity of the HPA axis in diet obesity models.

Effect of Tongdu Tiaoshen needling in treatment of chronic insomnia by regulating the hypothalamic-pituitary-adrenal axis / 针刺研究

OBJECTIVE: To investigate the clinical effect of Tongdu Tiaoshen needling in the treatment of chronic insomnia and its mechanism based on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: A total of 60 patients with chronic insomnia were randomly divided into treatment group and control group, with 30 patients in each group. In addition to the health education on sleep, the patients in the treatment group were given Tongdu Tiaoshen needling, i．e., electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), bilateral Shenmen (HT7), and bilateral Sanyinjiao (SP6), and those in the control group were given superficial acupuncture at Shousanli (LI10), Futu (ST32), and Feiyang (BL58) at both sides, once every other day and three times a week for 4 consecutive weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality and efficiency of sleep, and ELISA was used to measure the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). RESULTS: After treatment, the treatment group had significant reductions in the total PSQI score and the score of each component of PSQI (P<0.01), and the control group had significant reductions in the total PSQI score (P<0.01) and the scores of all components except sleep duration (P<0.05); compared with the control group, the treatment group had significantly lower total PSQI score and the score of each component (P<0.01). After treatment, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.05，P <0.01), and compared with the control group, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.01，P<0.05). CONCLUSION: Tongdu Tiaoshen needling has a good clinical effect in the treatment of chronic insomnia and can significantly improve the sleep condition of patients with chronic insomnia, possibly by reducing the hormones associated with the HPA axis.

Effect of Lepidium meyenii (Maca) on neurotransmitter level and neuro-endocrine-immune network of deficiency-cold and deficiency-heat syndrome rats / 中国中药杂志

The aim of this paper was to study the effect of Lepidium meyenii(Maca) on cyclic nucleotides, neurotransmitter levels and hypothalamic-pituitary-adrenal axis and immunization of deficiency-cold and deficiency-heat syndrome rats, in order to explore the cold and hot medicinal properties of Maca. SD rats were divided into blank group, deficiency-cold syndrome group, Cinnamomi Cortex of deficiency-cold syndrome(30 g·kg~(-1)) group, high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)), deficiency-heat syndrome group, Phellodendri Chinensis Cortex(PCC) of deficiency-heat syndrome(5 g·kg~(-1)), and high and low-dose Maca groups(2.4, 1.2 g·kg~(-1)). The rats were treated with intramuscular injection of hydrocortisone(20 mg·kg~(-1)) or dexamethasone sodium phosphate(0.35 mg·kg~(-1)) for 21 days to set up the deficiency-cold and deficiency-heat model. The levels of cAMP, cGMP, NE, DA, 5-HT, CRH, ACTH, CORT and IgM, IgG, C3, C4 were detected by radio immunoassay. Both the high-dose Maca group and the low-dose Maca group can significantly improve the overall state and body weight of rats with deficiency-cold syndrome(P<0.01, P<0.05), significantly increasing cAMP, cAMP/cGMP, NE, DA, ACTH(P<0.01, P<0.001), and significantly decreasing 5-HT(P<0.01, P<0.001). However, high-dose and low-dose Maca groups could not improve the deficiency-heat syndrome, and the levels of cAMP, cGMP, cAMP/cGMP, NE, DA, 5-HT and ACTH were not statistically significant. Maca had a significant regulatory effect on CORT, IgM, IgG and C3 content of rats with deficiency-cold and deficiency-heat syndrome(P<0.01, P<0.05, P<0.001). Maca showed the same effect with Cinnamomi Cortex in adjusting the levels of deficiency-cold rats, but in opposition to Phellodendri Chinese Cortex. This paper confirmed that Maca was slightly warm based on its effect on cyclic nucleotide levels and neuro-endocrine-immune networks by the pharmacological experimental method.

Monoaminergic system and HPA axis dysfunctions in attention deficit hyperactivity disorder / 国际儿科学杂志

Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and adolescents.Its etiology and pathogenesis are still not clear.The disorder of monoamine oxidase function in the central nervous system that can result in abnormal catabolism of monoamine neurotransmitters,then lead to alteration of dopamine/norepinephrine levels,which is believed to be associated with ADHD behavior.Besides,dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is also involved in the pathogenesis of ADHD.In this review,the interaction between the monoaminergic system and HPA axis and its possible mechanism related with ADHD will be systematically summed up based on recent research.