Protective effect of saikosaponin b2 on corticosterone induced PC12 cell injury based on cell metabonomics / 中国药理学与毒理学杂志

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Effect of gynostemma pentaphyllum saponins on pituitary⁃adrenal axis induced by hypoxia in rats / 安徽医科大学学报

Objective @#To observe the effect of hypoxia on pituitary adrenal axis in rats and the therapeutic effect of Gynostemma pentaphyllum saponins(GPs)intervention. @*Methods @# 50 male SD rats were randomly divided into normoxia control group , hypoxia control group , and hypoxia + GPs low , medium , and high dose intervention groups , with 10 rats in each group. Rats in the normoxia group were kept in a normoxia animal room for 28 days , while rats in the hypoxia group and drug intervention group were kept in a low⁃pressure oxygen chamber for 28 days. Among them , hypoxia + GPs low , medium and high dose groups of rats were gavaged daily with GPs of 40 mg/kg , 80 mg/kg , and 160 mg/kg , respectively. After 28 days , rats were killed in batches , their body weight and pituitary weight were measured , and pituitary index was calculated ; HE staining method was used to observe the morphology and structure of rat pituitary gland ; immunohistochemical and Western blot methods were used to observe the expression level of pituitary adrenocorticotropin ( ACTH) protein in rats ; ELISA method was used to observe serum ACTH and corticosterone ( CORT) concentrations in rats. @*Results @# Hypoxia had no significant effect on pituitary gland morphology and quality in rats. Hypoxia might induce the expression of rat pituitary ACTH protein and an increase in serum ACTH and CORT concentrations , while GPs might reduce the expression of rat pituitary ACTH protein and serum ACTH and CORT concentrations induced by hypoxia. @*Conclusion@# GPs have a significant effect on the pituitary adrenal axis induced by hypoxia in rats , and there is a dose⁃effect relationship between GPs and effect.

Role of an enriched environment in ameliorating early life stress-induced changes in structure and functions of hippocampus and amygdala in rats

Objectives: This study aimed to understand whether an enriched environment (EE) in adulthood benefits in mitigating the early life stress-induced changes in the structure and functions of the hippocampus and amygdala. Materials and Methods: Male Wistar rats were exposed daily for 6 h to early maternal separation and isolation (MS) stress from postnatal days (PND) 4–14 and later at PND 60–70 days subjected to EE, while, the normal control (NC) rats were not subjected to stress but reared with the mother under standard housing conditions. The effects of MS and EE on adulthood behaviour were not subjected to stress but assessed by measuring the ambulatory, repetitive and anxiety-like behaviour. The study has also done the plasma corticosterone concentrations. The dendritic remodelling in the amygdala and hippocampus was assessed using the Golgi cox staining approach. Finally, the present study compared the reactive oxygen species-induced lipid peroxidation and total antioxidant capacity in MS rats as an indirect measure of oxidative stress to study the impact of MS stress on the limbic circuit and peripheral organs. Results: MS rats showed increased anxiety and lower plasma corticosterone levels. The pyramidal neurons’ dendritic plasticity displayed a different pattern, with shrinkage in the CA1 hippocampal neurons and hypertrophy in the amygdala’s primary neurons. Variations in antioxidant activity and peroxidation observed in NC to MS across tissues indicate the occurrence and management of oxidative stress in MS. The 10 days of EE in young adulthood helped to reduce MS stress-induced structural abnormalities in hippocampal and amygdala pyramidal neurons, as well as anxiety and plasma corticosterone levels. Conclusion: These findings together indicate that exposure to adverse experiences may cause harmful effects on brain plasticity and behaviour in young adulthood. Exposure to EE may be beneficial in reducing the early life stress-induced pathophysiology later in life.

Sensory and sympathetic nerves are involved in the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis rats / 中国针灸

OBJECTIVE@#To investigate the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis model rats, as well as the relationship between sensory and sympathetic nerves and the formation of sensitized area, and to initially reveal the partial physical-chemical characteristics of the sensitized area in the colitis model rats.@*METHODS@#Thirty-five male SD rats were randomly divided into a control group (n=10), a model group (n=18) and a guanethidine group (n=7). 5% dextran sulfate sodium (DSS) was adopted for 6-day free drinking to establish colitis model in the model group and the guanethidine group. On day 6 and 7, in the guanethidine group, guanethidine solution (30 mg/kg) was injected intraperitoneally for sympathetic block. On day 7, after injection of evans blue (EB) solution, the EB extravasation areas on the body surface were observed to investigate the distribution and physical-chemical characteristics of the sensitized area. The control area was set up, 0.5 cm away from the sensitized area, and with the same nerve segment innervation. Disease activity index (DAI) score of rats was compared between the normal group and the model group, and the morphological changes in the colon tissue were investigated with HE method. Using infrared thermal imaging technology and laser speckle flow imaging technology, skin temperature and blood infusion were determined in the sensitized area and the control area of the rats in the model group. Immunofluorescence technique was adopted to observe the expression levels of the positive nerve fibers of substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and the correlation with blood vessels; as well as the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-hydroxytryptamine (5-HT) in skin tissue in the sensitized area and the control area of the rats in the model group. MSD multi-level factorial method and ELISA were applied to determine the contents of pro-inflammatory and anti-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, IL-4 and IL-10) and anti-inflammatory substance corticosterone (CORT).@*RESULTS@#Sensitization occurred at the T12-S1 segments of the colitis model rats, especially at L2-L5 segments. Compared with the normal group, DAI score was increased in the rats of the model group (P<0.05), and the colonic mucosal damage was obvious, with the epithelial cells disordered, even disappeared, crypt destructed, submucosal edema and a large number of inflammatory cells infiltrated. In comparison with the control area, the skin temperature and blood infusion were increased in the sensitized area of the model group (P<0.05, P<0.01); as well as the expression levels of the positive nerve fibers of SP, CGRP and TH of skin tissue (P<0.05), which was specially distributed in peripheral vessels, the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-HT of the skin tissue were all expanded (P<0.05) in the sensitized area of the model group. Compared with the model group, the number of sensitized areas was reduced in the guanethidine group (P<0.05). In comparison with the control area of the model group, in the sensitized area, the contents of pro-inflammatory cytokines, e.g. TNF-α, IL-1β and IL-6, and the anti-inflammatory substance CORT of skin tissue were all increased (P<0.05); and the contents of IL-6 and TNF-α were negatively correlated with CORT (P<0.05).@*CONCLUSION@#The sensitized areas on the body surface of colitis rats are mainly distributed in the L2-L5 segments. Sensory and sympathetic nerves are involved in the acupoint sensitization, and the sensitized areas may have the dynamic changes in pro-inflammatory and anti-inflammatory substances.

The extent of involvement of ouabain, hippocampal expression of Na+/K+-ATPase, and corticosterone/melatonin receptors ratio in modifying stress-induced behavior differs according to the stressor in context

The aim of this study was to assess the effect of two types of stressors, regarding the extent of involvement of ouabain (OUA), hippocampal sodium/potassium ATPase (NKA) expression, and the hippocampal corticosterone receptors (CR)/melatonin receptors (MR) expression ratio, on the behavioral and cardiovascular responses and on the hippocampal cornu ammonis zone 3 (CA3) and dentate gyrus (DG). Thirty adult male Wistar albino rats aged 7-8 months were exposed to either chronic immobilization or a disturbed dark/light cycle and treated with either ouabain or vehicle. In the immobilized group, in the absence of hippocampal corticosterone (CORT) changes, rats were non-responsive to stress, despite experiencing increased pulse rate, downregulated hippocampal sodium/potassium pump, and enhanced hippocampal CR/MR expression ratio. Prolonged darkness precipitated a reduced upright attack posture, with elevated CORT against hippocampal MR downregulation. Both immobilization and, to a lesser extent, prolonged darkness stress resulted in histopathological and ultrastructural neurodegenerative changes in the hippocampus. OUA administration did not change the behavioral resilience in restrained rats, despite persistence of the underlying biochemical derangements, added to decreased CORT. On the contrary, with exposure to short photoperiods, OUA reverted the behavior towards a combative reduction of inactivity, with unvaried CR/MR and CORT, while ameliorating hippocampal neuro-regeneration, with co-existing NKA and MR repressions. Therefore, the extent of OUA, hippocampal NKA expression, and CR/MR expression, and subsequent behavioral and cardiac responses and hippocampal histopathology, differ according to the type of stressor, whether immobilization or prolonged darkness.

The Amygdala Responds Rapidly to Flashes Linked to Direct Retinal Innervation: A Flash-evoked Potential Study Across Cortical and Subcortical Visual Pathways / 神经科学通报·英文版

Rapid detection and response to visual threats are critical for survival in animals. The amygdala (AMY) is hypothesized to be involved in this process, but how it interacts with the visual system to do this remains unclear. By recording flash-evoked potentials simultaneously from the superior colliculus (SC), lateral posterior nucleus of the thalamus, AMY, lateral geniculate nucleus (LGN) and visual cortex, which belong to the cortical and subcortical pathways for visual fear processing, we investigated the temporal relationship between these regions in visual processing in rats. A quick flash-evoked potential (FEP) component was identified in the AMY. This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC, which was assumed to be an important area in visual fear. This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection, but was diminished by RU38486, a glucocorticoid receptor blocker. By injecting a monosynaptic retrograde AAV tracer into the AMY, we found that it received a direct projection from the retina. These results confirm the existence of a direct connection from the retina to the AMY, that the latency in the AMY to flashes is equivalent to that in the sensory thalamus, and that the response is modulated by glucocorticoids.

Corticosterone induced D-serine release deficit play an important role in long-term potentiation impairment by corticosterone in perforant path-dentate gyrus pathway / 中国药理学与毒理学杂志

OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation (LTP) and cognitive impairment induced by stress or corticosterone. However, other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment. The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms. METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation (HFS) to induce LTP impairment. NMDA receptor antagonists and agonists were administrated by icv. RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice. Corticosterone increased the gluta?mate level in hippocampal tissues, neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP, while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone, suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticoste?rone. Further results showed that the level of D-serine and its precursor L-serine did not change. D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1 (ASC-1) in the cell membrane was decreased and increas?ing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticoste?rone. CONCLUSION Taken together, this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction, which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.

Effect of dietary metabolic energy on growth performance, blood homeostasis in ducks under heat stress-related climate change

Aim: This study was carried out to investigate the effect of dietary metabolic energy on growth performance, homeostasis of blood biochemical parameters, immunoglobulin G (IgG), and corticosterone in meat duck exposed to heat stress.Methodology: A total of 320 meat ducks (Cherry valley, Anas platyrhynchos) were randomly allotted into five groups. In all experimental treatment groups, dietary crude protein content was fixed at 18%. metabolic energy level for the control group (thermononeutral temperature, 26°C) was set at 3000 kcal kg-1, while metabolic energy levels for heat stress groups were set at 2900, 3000, 3100 or 3200 kcal kg-1. Heat stress conditions were artificially induced at 36°C with relative humidity of 70% once daily (from 11:00 to 16:00 hr) during finisher periods (day 22 to 42). Results: Compared to control group, heat stress groups with different metabolic energy showed significant decrease in body weight gain, feed intake, red blood cell, and platelets. Heat stress groups with different metabolic energies showed significant increase in feed conversion ratio, blood lipid profiles, aspartate aminotransferase, alanine transferase, electrolytes, pH, gas concentration, immunoglobulin G, and corticosterone compared to the control group.Among heat stress groups, red blood cells and platelets were significantly higher in the heat stress group with metabolic energy of 3000 compared to those in other groups. Blood IgG and corticosterone levels were significantly lower in 2900 and 3000 groups than those in heat stress groups with metabolic energy of 3100 and 3200. Interpretation: The results of this study suggest that dietary metabolic energy 3000 kcal kg-1 level can improve the growth performance of meat duck exposed to heat stress by modulating homeostasis of blood biochemical parameters.

Saffron (Crocus sativus) aqueous extract reverses the hypothalamus-pituitary-adrenal axis activity in rat model of post-traumatic stress disorder

Abstract Crocus sativus L., Iridaceae, has been used worldwide in traditional medicinefor treatment ofsome neurological disorderssuch as depression. Post-traumatic stress disorder is a mental disorder developed in peoplewho experience stressful events. Since stress has been proposed tocause thehypothalamic-pituitary-adrenal axis malfunction in post-traumatic stress disorder patients, this study aimed at investigating the effect of saffron aqueous extract on hypothalamic-pituitary-adrenal axis activity in rats of post-traumatic stress disorder model. Here, Post-traumatic stress disorder animals received an acute electro foot shock; however, 5 min before the stress session, these animals received an intra-cerebral-ventricular (10 µg/rat) infusion of either saffron aqueous extract or saline. Twenty one days later, they were re-exposedto the stress box withoutinducing stress, andthen were examined for their freezing behavior. The impact of stress and saffron aqueous extract on serum corticosterone, corticotrophin releasing hormone gene expression in hypothalamus and glucocorticoid receptor gene expression in pituitary gland werethen evaluated on day 28. Intra-cerebral-ventricular injection of saffron aqueous extract resulted in an increase in serum corticosterone level and reduced symptoms of freezing behavior, and corticotrophin releasing hormone and glucocorticoid receptor gene expression in post-traumatic stress disorder groups.Saffron administration could improve the symptoms of stress-induced post-traumatic stress disorder, possiblythrough the adjustment ofhypothalamic-pituitary-adrenal axis function.

Involvement of mitochondrial apoptotic pathway and MAPKs/NF-κ B inflammatory pathway in the neuroprotective effect of atractylenolide III in corticosterone-induced PC12 cells / 中国天然药物

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.

Expression and significance of serum corticosterone in rats with different burn degrees / 中国中西医结合急救杂志

Objective To investigate the changes of serum corticosterone and inflammatory factors in rats with different burn degrees. Methods One hundred and fifty male healthy Wistar rats were randomly divided into normal control group, moderate and severe burn hormone treatment groups, and moderate and severe burn physiological saline treatment groups, each group with 30 rats. After anesthesia, the rat models with burn Ⅱ,Ⅲ degrees of 30% back surface area were replicated; the burn, fluid infusion and steroid therapy were not carried out in the normal control group. After modeling, the moderate and severe burn hormone treatment groups were given intra-abdominal cavity injection of hydrocortisone 200 mg/d; while in the moderate and severe burn normal saline treatment groups, normal saline 4 mL·kg-1·d-1 was injected into the abdominal cavity. The dynamic changes of serum corticosterone, tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) levels were detected at 1, 4, 12 hours and 1, 3 and 7 days after burn injury in each group. Results The levels of serum corticosterone at different time points after moderate and severe burn injury treatment were higher than those in normal control group, the degree of increase at 4 hours after injury in severe burn saline treatment group was more significant than that in moderate and severe burn hormone treatment groups and moderate burn saline treatment group (ng/L: 200.45±2.63 vs. 110.56±9.23, 146.02±3.28, 160.02±8.22). Except the level at 1 hour after injury in the moderate and severe burn hormone treatment groups, the TNF-αlevels in all the other groups at different time points were significantly higher than those in the normal control group (all P < 0.05); the IL-6 levels in various treatment groups were all higher than the IL-6 level in the normal control group, moreover, the increase degree on 1 day after injury in the severe burn saline treatment group was more obvious than the degrees in the moderate and severe burn hormone treatment groups and the moderate burn saline treatment group [TNF-α(ng/L): 39.78±4.30 vs. 15.99±1.40, 20.58±2.10, 25.98±1.60, IL-6(ng/L): 210.20±6.70 vs. 125.45±3.10, 149.81±4.20, 161.40±3.80, all P < 0.05]. Conclusion The burn stress may lead to the significant increase of serum corticosterone level in rats, and the stress dose of hydrocortisone has a certain regulatory effect on serum corticosterone and inflammatory factors in rats after different degrees of burn.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.

Effect of yueju pill on depressive-like behavior and neurogenesis in corticosterone induced mice / 中国药理学通报

Aim: To investigate the effects of Yueju pill on depressive-like behavior and neurogenesis in chronic corticosterone (CORT) induced mice. Methods: Male C57BL/6N mice received chronic administration of CORT as well as Yueju pill. Behavioral tests were performed after the completion of treatment. The number of Ki67+ cells in the hippocampal DG region of each group was counted by immunohistochemistry test. Meanwhile, the expression levels of PKA, ERK and CREB were detected by Western blot. Results: The sucrose preference notably decreased (P < 0. 05) in CORT-induced mice in SPT, and it was raised obviously after Yueju treatment. The TST and NSF test displayed the similar results. The immunohistochemistry showed that the number of Ki67+ cells in the hippocampus DG significantly decreased in CORT-induced mice, while the number of Yueju group apparently increased (P < 0. 05). Western blot showed that compared with control group, the protein expressions of PKA-ERK-CREB pathway were down-regulated in CORT-induced mice, which were up-regulated after Yueju treatment (P < 0. 05). Conclusions: In CORT induced mice, Yueju pill can enhance the hippocampal neurogenesis by activating the PKA-ERK-CREB signaling pathway to display antidepressant-like effect.

Effects of high-fat diets on biochemical profiles and morpho- quantitative characteristics of C57BL/6 mice adrenal glands / Efectos de la dieta alta en grasa sobre el perfil bioquímico y las características morfo-cuantitativas de la glándula suprarrenal de ratón C57BL/6

According to the information provided by the World Health Organization (WHO), overweight and obesity are the fifth leading causes of death in the world. Due to the alarming increase of this disorder in recent years, studies have been carried out to evidence harmful effects on human or animal tissues. Our objective was to evaluate the morphological and physiological changes of C57BL/6 mice adrenal glands (AGs), associated with high fat diets (HFDs), we used 14 male mice, 5 months old, fed for 14 weeks according to two diets. The standard chow group (SC) was fed AIN-93M and the high fat group (HF) was fed AIN-93M-HF. At the end of the experiment, biometric analysis was performed and euthanasia was performed. Blood was then extracted for biochemical analysis and AGs were processed for mesoscopic, histological, morphometric and stereological studies. We used Student's t-test (p<0.05) for statistical analysis. SC group showed a lower weight (29.67±1.28 g) with respect to the HF group (38.46±4.68 g, p=0.002). COL-T, HDL-C, TG and CORT analysis revealed differences between SC group and HF (p≤0.001). Focally, in the fasciculate area, there was an increase in the core-cytoplasm ratio and a greater lipid vacuole presence and size. There was a significant reduction (p=0.001) in Vvfas=7.365±3.326 % of the HF group fasciculate area compared to SC group (Vvfas=9.619±4.548 %). Obesity induced by HF diets affects adrenal gland physiology and morphology of mice. Our results suggest that both the percentage of fat as well as the time of administration of the diet, produce a diurnal reduction of corticosterone, which could be due to an increase in the metabolic clearance of this hormone and not to the inhibition of the Hypothalamus-Pituitary-Adrenal (HPA) axis.

De acuerdo a la información entregada por la OMS, el sobrepeso y la obesidad son el quinto factor principal de riesgo de muerte en el mundo. Debido al aumento alarmante de este trastorno en los últimos años, estudios evidencian efectos perjudiciales sobre tejidos humanos y animales. Por lo tanto, nuestro objetivo fue evaluar los cambios morfo-fisiológicos de la glándula suprarrenal de ratones C57BL/6 asociado a dietas altas en grasas. Utilizamos 14 ratones machos, de 5 meses, alimentados por 14 semanas con dos dietas. Grupo dieta estándar (SC), alimentados con AIN-93M y grupo alto en grasa (HF), alimentado con AIN- 93M-HF. Al finalizar el experimento, se realizó el análisis biométrico y se efectuó la eutanasia. Posteriormente, se extrajo sangre para el análisis bioquímico y cada glándula suprarrenal fue procesada para el estudio mesoscópico, histológico, morfométrico y estereológico. Para el análisis estadístico se utilizó la prueba t de Student (p<0,05). El grupo SC mostró un menor peso (29,67±1,28 g) respecto al grupo HF (38,46±4,68 g; p=0,002). El análisis del COL-T, HDL-C, TG y CORT reveló diferencias entre el grupo SC y HF (p≤0,001). En la zona fasciculada, focalmente, se observó aumento en la relación núcleo-citoplasma y, mayor presencia y tamaño de vacuolas lipídicas. Hubo una reducción significativa (p=0,001) en VVfas=7,365±3,326 % de la zona fasciculada del grupo HF, en comparación al grupo SC (VVfas=9,619±4,548 %). La obesidad inducida por la dieta HF afecta la fisiología y morfología de la glándula suprarrenal de ratones alimentados con dietas altas en grasas. Nuestros resultados sugieren que tanto el porcentaje de grasa, así como el tiempo de administración de la dieta, producen una reducción diurna de la corticosterona, lo que podría ser debido a un aumento en el aclaramiento metabólico de esta hormona y no a la inhibición del eje Hipotálamo-Hipófisis-Adrenal.

Corticosterone inhibits LPS-induced expression of NLRP3 in mouse mac-rophages and its relation with XO / 中国病理生理杂志

AIM:To investigate the inhibitory effect of corticosterone(CORT)on lipopolysaccharide(LPS)-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and its relation with xan-thine oxidase(XO).METHODS:An inflammatory model of mouse macrophage RAW 264.7 was established by stimula-ting with LPS.Total cellular protein was extracted after the macrophages were treated with CORT at different concentrations (0~900 μg/L).The protein levels of NLRP3 and caspase-1 were determined by Western blot.According to the treat-ments,the macrophages were divided into control group,LPS group,LPS+CORT group and LPS+allopurinol group.Cell components were extracted at 0,0.5,1,1.5 and 2 h.The protein levels of NLRP3 and XO were determined by Western blot,and the mRNA expression of NLRP3 and XO was detected by real-time PCR.RESULTS: CORT at 700 μg/L and above significantly inhibited the expression of NLRP 3 and the activation of caspase-1 in the macrophages induced by LPS (P<0.05).Compared with LPS group, the expression of NLRP3 and XO in LPS +CORT group was inhibited(P <0.05),and the expression of NLRP3 in LPS+allopurinol group was also reduced(P<0.05).CONCLUSION: High concentration of CORT inhibits the expression of NLRP 3 in LPS-induced mouse macrophages,which is associated with XO. The inhibitory effect of CORT may be related to the reduction of XO expression.

Chronic injection of corticosterone induces depression and impairment of learning and memory in mice / 中国比较医学杂志

Objective To Study the depression-like behavior and impairment of learning and memory induced by chronic injection of corticosterone in mice. Methods Forty male C57BL/6J mice were divided into four groups, the control group, and the corticosterone groups(20,40,80 mg/kg). The mice received subcutaneous injection of corticosterone once a day for 21 days. The depression-like behaviors were detected by open field test(OFT), tail suspension test(TST)and forced swimming test(FST). To select the most effective dose of corticosterone, TST, FST, object location recognition test, and Morris water maze(MWM)test were used to study the corticosterone-induced depression-like behaviors and impairment of learning and memory in the mice. Results Compared with the control group, the movement distance and duration were significantly decreased in the corticosterone injection groups(40,80 mg/kg)(P< 0.01 or P< 0.05). In the TST group,the immobilization time was significantly increased in the corticosterone injection group(40,80 mg/kg)(P< 0.05). The TST and FST showed that the immobilization time of the corticosterone injection group(40 mg/kg)was significantly increased(P < 0.05). The object recognition test showed that the discrimination indexes of the object location recognition were decreased in the corticosterone injection group(40 mg/kg). The MWM test showed that the escape latency was increased(P< 0.05),and the number of crossing in target quadrant and the velocity in target quadrant were decreased(P< 0.05)in the corticosterone injection group(40 mg/kg). Conclusions Chronic injection of corticosterone can induce depression accompanied with learning and memory impairment in mice.

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 .

Alterations in Spontaneous Movement, Corticosterone, and Cytokines in Mice Exposed to 835 MHz Radiofrequency Radiation / 체질인류학회지

Although commercialization of mobile phones has raised much concerns about the effects of radiofrequency radiation on the human body, few experimental studies have been conducted on the effects of radiofrequency radiation on physiological homeostasis, immune and inflammatory responses. Therefore, we presently investigated the effect of 835 MHz radiofrequency radiation on spontaneous wheel exercise, hormone and cytokines levels in the plasm of mice. Mice were divided into 4 groups as control, exercise, radiofrequency radiation, radiofrequency radiation & exercise group. The body weight, corticosterone and blood cytokine levels were checked for 10 weeks. Followed by the exposure to radiofrequency radiation for 6 hours a day, the more increase in body weight was observed in the radiofrequency radiation & exercise group than in the spontaneous exercise group. When the amount of spontaneous exercise was measured for 10 weeks, the amount of exercise was increased in the both control and spontaneous exercise group, while the amount of exercise was decreased in the radiofrequency radiation group. To determine whether the homeostasis, immune and inflammatory responses are indirectly affected by radiofrequency radiation exposure, IL-1β, IL-6, IL-12 (p70), TNF-α, IFNγ, and GM-CSF were measured by ELISA kit, respectively. As a result, the blood levels of IL-6, IL-12 (p70) and TNF-α in the spontaneous exercise group were higher than that of control group, and each cytokine levels in the radiofrequency radiation & exercise group were lower than that of control group. However, the corticosterone, IL-1β, IFNγ and GM-CSF didn't show statistically significant differences in all groups. It has been confirmed that exposure to high frequency electromagnetic waves for a long time can affect the amount of exercise, body weight, and some inflammatory cytokines such as IL-6, IL-12 (p70) and TNF-α.

Gonadotrophic, prolactin, corticosterone, and gonadal hormones levels over 15 months in Giant Amazon River Turtles - Podocnemis expansa (Schweigger, 1812) (Testudines: Podocnemididae), in captive conditions / Gonadotrofinas, prolactina, corticosterona, e as hormonas sexuais durante 15 meses de Tartarugas da Amazônia - Podocnemis expansa (Schweigger, 1812) (Testudines: Podocnemididae), em condições de cativeiro

Abstract In order to achieve successful captive breeding the Podocnemis expansa, it is necessary to study their reproductive endocrinology. The purpose of this research was to evaluate and characterize plasma concentrations in gonadotrophic, gonadic, corticosterone and prolactin hormones from Giant Amazon Turtles under captive conditions. Blood samples were collected over a 15 month period. The samples were assayed by the use of radioimmunoassay, prolactin, corticosterone, LH, FSH, testosterone, 17β-estradiol and progesterone. We verified significant seasonal pattern increase in 17β-estradiol levels and decrease in progesterone levels in the course of a year, which indicates vitellogenesis. This is related to normal ovarian cycles and possibly to the functional integrity of the hypothalamus-pituitary-gonad axis of captive females. There were negative correlations between testosterone and corticosterone in the male samples, suggestive of stress (management stress) on the reproductive system. The plasma concentrations of gonadotrophic, gonadic, prolactin and corticosterone hormones may be used as a reference for further research and possible therapeutic approaches. The data collected during this research are unprecedented for this species and may serve as a reference for future research regarding the reproductive cycle of this turtle, also allowing reproductive management while in captivity. Information about these hormones must be gathered from wild populations during different periods of the year for better clarification of the reproductive physiology of this species.

Resumo Com o objetivo de obter reprodução em cativeiro de Podocnemis expansa, é necessário reunir o conhecimento a respeito de sua endocrinologia reprodutiva. O objetivo deste trabalho foi avaliar e caracterizar as concentrações plasmáticas de hormônios gonadotróficos, gonadais, corticosterona e prolactina em Tartarugas da Amazônia em condições de cativeiro. Amostras de sangue foram coletadas durante 15 meses. As amostras foram ensaiadas pelo uso de um radioimunoensáio, prolactina, corticosterona, LH, FSH, testosterona, 17β-estradiol e progesterona. Verificou-se aumento de padrão sazonal significativo nos níveis de 17β-estradiol e diminuição dos níveis de progesterona ao longo do ano, o que indica o recrutamento folicular. Isto está relacionado com ciclos ovarianos normais e possivelmente para a integridade funcional do eixo hipotálamo-hipófise-gônadas de fêmeas em cativeiro. Houve correlação negativa entre testosterona e corticosterona nas amostras do sexo masculino, sugestivos de efeito do estresse de manejo sobre o sistema reprodutivo. As concentrações plasmáticas de hormônios gonadotrofinas, gonadais, prolactina e hormônios corticosterona pode ser usado como referência para futuras pesquisas e possíveis abordagens terapêuticas. Os dados médios coletados durante a pesquisa são inéditos para a espécie e pode servir como referência para futuras pesquisas sobre o sistema reprodutivo da tartaruga, também permitindo manejo reprodutivo em cativeiro. Informações sobre esses hormônios devem ser recolhidas a partir de natureza selvagem em diferentes períodos do ano para melhor esclarecimento da fisiologia da reprodução desta espécie.