Serum Corticosterone Levels Research Articles

Experimental Chronic Prostatitis/Chronic Pelvic Pain Syndrome Increases Anxiety-Like Behavior: The Role of Brain Oxidative Stress, Serum Corticosterone, and Hippocampal Parvalbumin-Positive Interneurons.

Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle-aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin-positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ-carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety-like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety-like behavior in rats with CP/CPPS comparing to their sham-operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety-like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons.

Ameliorative property of ginger (Zingiber officinale) in minimising immunosuppression induced by arsenic in White Pekin ducks (Anas platyrhynchos)

Due to industrialisation heavy metal toxicity is increasing day by day. The current research was performed to reduce the immunosuppressive effects of arsenic (As) by supplementing ginger in basal diet. About 120 White Pekin ducks of 7 days old were randomly allocated into 5 groups having 24 birds in each. Each group contained 3 replicates having 8 birds in each replicate and fed either basal diet as such (control/ T1); T2: 28 ppm As/L of drinking water + basal feed; T3: 28 ppm As/L of drinking water + dried ginger powder @ 100 mg/kg of basal feed; T4: 28 ppm As/L of drinking water + dried ginger powder @ 300 mg/kg of basal feed; T5: 28 ppm As/L of drinking water + dried ginger powder @ 1 g/kg of basal feed for 90 days. The decreased in body weight and FCR in T2 was improved significantly in T4 and T5. Ginger enhanced the activity of anti-oxidative enzymes in spleen tissue of As intoxicated birds. Suppressed immunity due to As toxicity were attenuated by ginger supplementation through enhanced phagocytic activity, phagocytic index, humoral and cell mediated immunity. Similarly, serum corticosterone level was significantly reduced in ginger treated birds than As intoxicated ducks. Besides above facts there were also histopathological alternations of spleen. It was concluded that, As exerts immunosuppressive effects and supplementation of ginger at 1 g/kg diet was effective in enhancing immunity and protecting the ducks from oxidative stress induced by As.

Protective role of Allium cepa Linn (onion) juice on maternal dexamethasone induced alterations in reproductive functions of female offspring of Wistar rats

Maternal treatment with dexamethasone induces oxidative stress in the reproductive structures of offspring. Consumption of Allium cepa Linn improves antioxidant status. This study was designed to evaluate the protective role of Allium cepa Linn juice on maternal dexamethasone induced alterations in reproductive functions of the female offspring of Wistar rats.Twenty lactating dams (180–200 ​g) were randomly assigned into four groups (n ​= ​5) on the day of parturition and treated as follows during lactation for 21 days: Control (5 ​ml/kg BW distilled water); Dexamethasone (60 ​μg/kg BW); Allium cepa (5 ​ml/kg BW); Dexamethasone ​+ ​Allium cepa (60 ​μg/kg BW ​+ ​5 ​ml/kg BW). The female offspring were separated at birth. Days of vaginal opening and first oestrus cycle, length and frequency of estrous cycle as well as serum hormonal profiles were assessed as measure of reproductive functions. Ovarian superoxide dismutase (SOD) activity, catalase activity and malondialdehyde (MDA) level were measured as indices of oxidative stress.Oestrous cycle length, frequencies of diestrus as well as the Ovarian MDA were significantly increased (p ​< ​0.05) in dexamethasone (DEX) group relative to control group. Serum 17β-oestradiol and corticosterone level in addition to SOD and catalase activities were significantly reduced (p ​< ​0.05) in DEX group relative to control. Co-administration of Dex with Allium cepa Linn juice reduced the oestrous length, frequency of diestrous as well as ovarian MDA. There was also a significant increase in serum 17β-oestradiol, ovarian SOD and catalase activity.The results suggest that Allium cepa could protect against alterations in reproductive functions of offspring induced by maternal treatment with dexamethasone during lactation in Wistar rats. The flavonoid constituent of onion may also help in reducing oxidative stress in the offspring.

Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH(4-7)-PGP (Semax).

We studied the effect of intraperitoneal administration ACTH(4-7)-PGP in doses of 5, 50, 150, and 450 μg/kg to Wistar male rats 12-15 min before modeling restraint stress on the morphofunctional state of the colon. In rats exposed to restraint stress, signs of atrophy and inflammatory reaction in the colon wall, changes in functional activity and number of mast cells, and increased serum level of corticosterone were observed. Administration of the peptide led to a decrease in corticosterone concentration, alleviated stress-induced pathomorphological changes, and promoted adaptation of the intestinal wall to stress. The positive effects of ACTH(4-7)-PGP can be determined by multifunctional nature of the physiological and pharmacological effects of the neuropeptide.

ニコチンは血清コルチコステロン量の増加を介した慢性予測不能軽度ストレスによるうつ様行動を緩解する

ニコチンは血清コルチコステロン量の増加を介した慢性予測不能軽度ストレスによるうつ様行動を緩解する

L. Cucurbita pepo modulates contact dermatitis in depressed rats through downregulation of proinflammatory cytokines and upregulation of antioxidant status.

IntroductionThe link between psychological stress and skin diseases, such as atopic dermatitis is established. Pumpkin was proved to have antioxidant, anti-inflammatory and accelerating wound healing potential.AimTo assess the efficacy of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving contact dermatitis (CD) in depressed rats compared to a standard treatment of CD and explore the mechanism behind this effect.Material and methodsThirty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression, then exposed to 1-fluoro-2,4-dinitrofluorobenzene (DNFB) for 2 weeks for induction of CD. The rats were then divided into 3 groups (n = 10 each); the positive control, Betamethasone-treated, and PE-treated groups. Depression was confirmed by the forced swim test and measuring the serum corticosterone level. Proinflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were measured in the skin and serum and their mRNA levels were assessed using qRT-PCR. Oxidant/antioxidant profile including levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) was assessed in the skin and serum. Histopathological assessment of skin samples was performed and CD4 and CD68 immunoexpression was assessed.ResultsThe used PE included a large amount of oleic acid (about 56%) and a small amount of linoleic acid (about 1%). The topical application of PE significantly attenuated inflammation and oxidative changes attributed to CD associated with chronic stress-induced depression comparable to the standard treatment of CD. PE significantly alleviated signs and histopathological score of CD (p < 0.001) through the significant down-regulation of pro-inflammatory cytokines and the significant up-regulation of antioxidants in the skin. Significant down-regulation (p < 0.001) of TNF-α, IL-6, COX-2 and iNOS gene expression in the PE-treated group confirmed the anti-inflammatory action of PE.ConclusionsThe pumpkin extract, applied topically in CD associated with depression, could be an alternative as well as preventive approach in treating CD. Anti-inflammatory and antioxidants activity of pumpkin is a proposed mechanism behind this effect. Further studies to test this effect on volunteer patients of CD are recommended.

Physical and psychological stress along with candle fumes induced-cardiopulmonary injury mimicking restaurant kitchen workers

Restaurant kitchens are work areas where involve strict and hierarchal environments that promote opportunity for bullying and workplace aggression and violence. These physical and psychological stress and fumes ultimately trigger severe occupational stress by disrupting the body's homeostasis that might induce cardiopulmonary injury. The study aimed to investigate the physical and psychological stress and candle fumes on cardiopulmonary injury in an animal model mimicking a restaurant kitchen worker. Social disruption stress (SDR) mice were exposed to scented candle fumes (4.5 h/d, 5 d/wk) in an exposure chamber for 8 weeks. Exposure to burning scented candles failed to reduce serum corticosterone level and increased proinflammatory cytokines levels and NF-ƙB activity in the lung. In addition, burning scented candle fumes synergistically increased SDR-induced serum LDH, CPK, CKMB levels, proinflammatory cytokines production as well as NF-ƙB activation in the lung and heart. Further, cardiac HIF-1α and BNP levels were also increased. We conclude that the physical and psychological stress along with candle fumes might induce cardiopulmonary injury in mice. These results could be extrapolated to restaurant kitchen workers.

Exercise-induced increases of corticosterone contribute to exercise-enhanced adult hippocampal neurogenesis in mice.

Adult hippocampal neurogenesis (AHN) is suppressed by chronic stress. The negative effect of stress is mainly attributed to increased levels of stress hormones (e.g. glucocorticoids, GCs). Exercise enhances AHN, yet it also stimulates GC secretion. To delineate the paradoxical role of GCs, we took the advantage of a unique mouse strain (L/L) which exhibits an inert response to stress-induced secretion of GCs to study the role of GCs in exercise-induced AHN. Our results showed that basal corticosterone (CORT), the main GCs in rodents, levels were similar between the L/L mice and wild-type (WT) mice. However, levels of CORT in the L/L mice were barely altered and significantly lower than those of the WT mice during treadmill running (TR). AHN was enhanced by 4 weeks of TR in the WT mice, but not L/L mice. WT mice that received daily injection of CORT to evoke serum CORT levels similar to those during exercise for 4 weeks did not affect AHN, whereas injection with large amount of CORT inhibited AHN. Taken together, our results indicated that exercise-related elevation of CORT participates in exercise-enhanced AHN. CORT alone is not sufficient to elicit AHN and may inhibit AHN if the levels are high.

Peanut butter as an alternative dose delivery method to prevent strain-dependent orogastric gavage-induced stress in mouse teratogenicity studies

IntroductionAnimal-based studies are essential for assessing toxicity to environmental pollutants, especially when the potential targets are specific developmental time points, teratogenic, or multi-organ systems that cannot be modeled in vitro. Orogastric gavage is a widely used technique for exposure because of its increased accuracy of dose administration over free feeding. However, repeated use of this method has been reported to cause physiological stress on the exposed animals that could interfere with interpretation of results. Previous studies have shown that genetic background also contributes to the level of stress and can affect individual response. MethodsTo evaluate the impact of stress on repeated orogastric gavage, we exposed C67BL/6J and 129S1/SvImJ inbred mouse strains to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), a potent xenobiotic that has been extensively studied in vivo. Pregnant females were dosed for ten days after mating using orogastric gavage with olive oil as vehicle or through diet using peanut butter as vehicle. Serum corticosterone levels, body weight, and reproduction endpoints were measured to evaluate levels of stress induced by the dosing technique. ResultsThe levels of stress caused by orogastric gavage was strongly dependent on strain background and on the phenotypic endpoint. Orogastric gavage-induced stress was more detrimental in 129S1/SvlmJ pregnant female mice than in C57BL/6J. ConclusionThese results show that administration of xenobiotics via controlled diet can improve the reproducibility and rigor of exposure studies requiring orogastric delivery.

Intensive treadmill training promotes cognitive recovery after cerebral ischemia-reperfusion in juvenile rats

Rehabilitation training is routine for children who experience stroke, but its protective mechanism remains unclear. To study the effect of treadmill training intensity on hippocampal synaptic plasticity after cerebral ischemia, a model of middle cerebral artery occlusion (MCAO)/reperfusion was established in young rats to simulate childhood ischemic stroke. The rats were randomly allocated into five groups: sham operation, MCAO, low-intensity exercise and MCAO (5 m/min), medium-intensity exercise and MCAO (10 m/min), and high-intensity exercise and MCAO (15 m/min). Intervention was continued for 14 days, and a series of experimental tests were conducted.After MCAO, the juvenile rats exhibited a series of morphological and functional alterations, including changes in their neurobehavior and cerebral infarct volumes. Compared with control rats, MCAO rats had a longer escape latency and crossed fewer platforms in the water maze test and exhibited decreased hippocampal neuron density and Synapsin I and PSD95 expression. Furthermore, MCAO rats exhibited synapse morphology changes and abnormal serum levels of lactic acid and corticosterone. Treadmill training effectively reduced the neurobehavioral scores and cerebral infarction volumes, with medium-intensity training showing the best effect. Treadmill training shortened the escape latency, increased the number of platform crossings, and improved the spatial cognitive abilities of the rats, with the medium intensity training having the best effect on spatial learning/memory efficiency. Treadmill training increased the neuron density in the hippocampus, with the medium-intensity training resulting in the highest density. Treadmill training had a positive effect on the expression of Synapsin I and PSD95, with the medium-intensity training showing the strongest effect. Treadmill training improved the sub-microstructure synapse morphology, with the medium-intensity training demonstrating the best effect. Treadmill training increased the plasma levels of lactic acid and corticosterone, with the high-intensity training having the most obvious effect.Treadmill training can provide neuroprotection by promoting hippocampal synaptic plasticity, with medium-intensity training showing the most optimal effects.

Müziğin strese bağlı indüklenen hormonlar ve oksidatif stres üzerine etkisi

Purpose: Perinatal stress, anxiety, and depression have been thought having influences on the developmental period of organisms. In this study, we aimed to investigate the effects of different types of music exposure during perinatal period on depression-like behavior, serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and parathyroid hormone (PTH) as well as serum oxidative stress index in rats. &#x0D; Materials and Methods: Pregnant Wistar albino rats were randomly divided into four cages; the control group (no music exposure), the classical music group (Canon in D Major/ Johann Pachelbel, 60 dB), the traditional Sufi music group (Whirling Derwish/ Omar Faruk Tekbilek, 30 dB), and the rock music group (In Your Face/ Children of Bodom, 120 dB). Dams and pups in each music groups listened to their own music 1 hour/day from gestational day 10 to postnatal day 21. &#x0D; Results: According to the results of tail suspension test, the longer duration of immobility which shows the level of depression was increased in the classical music group compared to the control group. At hormonal level, significant alterations were obtained only in serum ACTH levels. It was increased in the classical music group, while decreased in the sufi music group compared to the control group. In addition, a marked increase in oxidative stress index was found in the rock music group compared to the control group. &#x0D; Conclusion: The sound intensity of music which is listened during the pregnancy has vital importance in the stress and depression level of offspring.

The PGE2 receptor EP3 plays a positive role in the activation of hypothalamic-pituitary-adrenal axis and neuronal activity in the hypothalamus under immobilization stress

BackgroundProstaglandin E2 (PGE2) binds to four receptor subtypes (EP1, EP2, EP3 and EP4) and plays an important role in response to stress. However, the identity of the receptor(s) responsible for PGE2 regulation of neuronal activity and signaling through activation of the hypothalamic-pituitary-adrenal (HPA) axis under immobilization stress is unknown. PurposeThe present study aimed to investigate the role of the hypothalamic PGE2 receptors in the activation of the HPA axis and neuronal activity in a rat model of stress. MethodsStress was induced by immobilization of the animals, after which the stress-induced profile of PGE2 receptor signaling in the rat hypothalamus was determined by real-time polymerase chain reaction and immunohistochemistry. The effect of a selective EP3 receptor antagonist on corticosterone concentrations and c-Fos immunoreactivity was measured. ResultsExpression of EP2 and EP3 receptor genes, but not EP1 and EP4, was increased following immobilization stress. The EP3 receptor was localized to the paraventricular nucleus (PVN) of the hypothalamus, and the integrated density of the EP3 receptor was increased after immobilization stress. Rats given L-798,106, a selective antagonist of the EP3 receptor, showed significant attenuation of stress-increased serum corticosterone levels. EP3 antagonist also significantly suppressed the increase in the gene expression of c-Fos and the number of c-Fos-immunoreactive cells in the PVN of the hypothalamus following immobilization stress. ConclusionsThese results suggest that immobilization stress may result in increased activation of the HPA axis and neuronal activity through regulating the function of the EP3 receptor.

Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine's Rapid Antidepressant Actions.

Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function.

Crassifoside H ameliorates depressant behavior in chronic unpredictable mild stress rats by improving HPA axis dysfunction and inhibiting inflammation in hippocampus

Purpose: To investigate the antidepressant mechanism of action of Crassifoside H (CH) from the rhizomes of Curculigo glabrescens (Hypoxidaceae) in chronic unpredictable mild stress (CUMS)-induced rats.Methods: CUMS-induced rat depressant model was established. Behavioral tests, viz, sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were applied to assess the antidepressant effect of CH. Enzyme linked immunosorbent assay (ELISA) was used to assess thelevels of corticosterone (CORT), TNF-α and IL-1β in serum. Protein expressions of TNF-α, IL-1β and NLRP3 in rat hippocampus were determined by Western blot.Results: Crassifoside H significantly ameliorated CUMS-induced depressant-like behavior as the serum CORT level of CUMS rats. CH remarkably decreased TNF-α and IL-1β levels in serum and hippocampus of CUMS rats. Moreover, Crassifoside H significantly inhibited NLRP3 activation inhippocampus.Conclusion: The findings demonstrate that Crassifoside H has antidepressant effect on CUMS rats. The mechanism of action of CH may be at least partly due to the improvement of hypothalamic-pituitaryadrenal (HPA) axis dysfunction by decreasing serum CORT. These findings suggest that Crassifoside H has a therapeutic potential for the management of depression.&#x0D; Keywords: Crassifoside H, Antidepression, Curculigo glabrescens, Hypoxidaceae, Hypothalamicpituitary- adrenal axis, Inflammation, Corticosterone

Abstract 15515: Cardiovascular Phenotyping of the APP23 Overexpressing Mouse Model of Alzheimer’s Disease Reveals Decreased Vascular Contractility

Background and Aim: Alzheimer’s disease (AD), the most common form of dementia, is characterized by noticeable neuropsychiatric symptoms and cognitive decline. Increasing epidemiological and experimental evidence highlights the occurrence of cardiovascular (CV) disease in the progression of AD. Therefore, we aimed to investigate the cardiovascular phenotype of the APP23 +/- overexpressing mouse model (APP23 +/- ). Methods: The current study presents the CV characterization of APP23 +/- mice (male, n=10) compared to C57BL/6 (male, n=24) at 6 months of age, including in vivo analysis of blood pressure (BP, CODA), aortic pulse wave velocity (aPWV), and echocardiography (high-frequency echocardiography, VEVO2100). Serum corticosterone levels and vascular smooth muscle cell (VSMC) phenotypic markers were ascertained via ELISA and qPCR. Data are presented as mean ± SEM. Results: At 6 month of age, APP23 +/- mice experience a lower survival rate compared to C57BL/6 littermates (39% vs. 100%, p=0.001) and APP23 +/- mice showed increased corticosterone levels compared to C57BL/6 mice (13.39 ± 5.15 vs. 2.30 ± 2.52 μg/mL, p=0.0025). Peripheral BP was increased (systolic BP: 110 ± 5 vs. 99 ± 3 mmHg, p=0.045; diastolic BP: 81 ± 5 vs. 71 ± 3 mmHg, p=0.09) with unaltered pulse pressure. Echocardiography revealed no differences in systolic and diastolic heart function. In vivo arterial stiffness was elevated in APP23 +/- mice (aPWV: 4.08 ± 0.3 vs. 2.94 ± 0.1 m/s, p=0.0004). Vascular reactivity studies showed decreased (32 %) adrenoreceptor-dependent contractions of the thoracic aorta from APP23 +/- mice. Endothelial-dependent (acetylcholine) and -independent (diethylamine nonoate) relaxations were unaffected. Contractile VSMC markers remained unchanged. Conclusion: In conclusion, APP23 +/- mice present with high serum corticosterone levels, elevated pulse wave velocity and decreased vascular contractility.

Exposure to eagle owl feces induces anti-predator behavior, physiology, and hypothalamic gene responses in a subterranean rodent, the plateau zokor (Eospalax baileyi)

Predator odors are natural stressors that induce anti-predator defensive responses, which have developed under evolutionary pressures to maximize the fitness of an individual to avoid dangerous confrontations. In this study, we analyzed the defensive responses of a subterranean rodent species, the plateau zokor (Eospalax baileyi), to predation threat, and examined the trade-offs between defensive responses and foraging. Plateau zokors were exposed to 1, 3, and 6 g of eagle owl (Bubo bubo) feces, and the anti-predator behavioral, hormonal, and hypothalamic corticotropin-releasing factor and c-fos mRNA expression responses were analyzed and compared with the control (distilled water). Exposure of the animals to owl feces led to significant reductions in both duration of feeding and amount of food consumed, while some defensive behavioral responses (e.g., freezing and rearing) were more significant in the exposed animals than in the control. Serum levels of adrenocorticotropic hormone and corticosterone in plateau zokors exposed to owl feces were significantly higher compared with the control. The hypothalamic corticotropin-releasing factor and c-fos mRNA expression levels of plateau zokors exposed to 1, 3, and 6 g owl feces increased significantly, concomitant with the amount of eagle owl feces presented. Owl feces induced various behavioral, hormonal, and hypothalamic gene expression changes in plateau zokors exposed to them. Some behavioral and gene expression (but not hormonal) responses appeared to be threshold dependent. Predator odors supersede other signals and can provide comprehensive information to prey during life-threatening events. The plateau zokor is a typical subterranean rodent living in dark and enclosed subterranean habitats. Owing to this special habitat, zokors may be able to recognize ground predator odors and respond defensively. We investigated changes in behavior, hormones, and the hypothalamic corticotropin-releasing factor and c-fos mRNA expression levels of the plateau zokor when exposed to different amounts of eagle owl feces. We believe that our study makes a significant contribution to the literature because our results support the predation risk allocation hypothesis, showing that eagle owl feces inhibit foraging and induce various anti-predatory behavioral and neuroendocrine responses in plateau zokors.

Increasing γ-Aminobutyric Acid Content in Vegetable Soybeans via High-Pressure Processing and Efficacy of Their Antidepressant-Like Activity in Mice.

This study applied high-pressure processing (HPP) technology to enrich the gamma aminobutyric acid (GABA) content in vegetable soybeans and evaluated its antidepressant efficacy on mice, with depression induced by the unpredictable chronic mild stress (UCMS) model. The optimal conditions for HPP, storage time, and storage temperature, as well as antidepressant-like effects of vegetable soybeans, were evaluated and discussed. HPP could effectively and significantly increase GABA content in soybean, with optimum conditions at 200 MPa. The GABA content in the whole vegetable soybean was 436.05 mg/100 g. In mice animal tests, the tail suspension test (TST) showed that the immobility time of the GABA group was significantly shorter than that of the control group. The total travel distance in the open field test (OFT) showed that depressed mice fed with the GABA feed exhibited exploratory behavior. The GABA group showed a significantly higher degree of sucrose preference than the control group. Both results indicate that the GABA feed could effectively alleviate depressive symptomatology. Regarding biochemical parameters, the fecal and serum corticosterone (CORT) levels in the control group increased to 104.86 pg/mg after the onset of depression. In contrast, the fecal CORT level in the GABA group was significantly reduced to 23.98 pg/mg and was comparable to that in the control group (33.38 pg/mg). Reduced serum CORT level in the GABA group suggests an improvement in depressive symptomatology. The serotonin concentration was maintained in the GABA group after the induction of depression, suggesting its preventive activity. The HPP GABA-enriched soybeans exerted modulatory effects on the behaviors of depressed mice and displayed a potential for commercialization.

Effect of polyphenol extract from Zanthoxylum bungeanum Maxim. on endocrine hormones and monoamine oxidase activity in a mouse model of climacteric depression

Purpose: To investigate the effects of polyphenol extract from Zanthoxylum bungeanum Maxim. (ZPPC) on endocrine hormones, monoamine oxidase activity and behavior in a mouse model of climacteric depression.Methods: Institute of Cancer Research (ICR) female albino mice (n = 50) weighing 24 – 26 g (mean wt = 25.0 ± 1.0 g) were randomly assigned to five groups of ten rats each: normal control group, negative control, and ZPPC (50 mg/kg), ZPPC (100 mg/kg) and ZPPC (200 mg/kg) groups. Depression was induced in the mice via oral administration of moclobemide at a dose of 20 mg/kg, and intraperitoneal injection of imipramine (20 mg/kg) 1 h and 30 min, before treatment. Tail suspension, forced swimming and voluntary activity tests were performed on the mice. The activity of monoamine oxidase (MAO) in mouse brain and the levels of endocrine hormones were also determined.Results: Treatment of depressed mice with ZPPC significantly and dose-dependently increased their tail suspension and immobility time (p &lt; 0.05). The activity of monoamine oxidase in the brains of mice in the negative control group was significantly higher than that of normal control mice, but was significantly and dose-dependently reduced by ZPPC treatment (p &lt; 0.05). Similarly, treatment of depressed mice with ZPPC significantly and dose-dependently reduced their serum adrenocorticotropin and corticosterone levels (p &lt; 0.05).Conclusion: The results of this study indicate that ZPPC exerts antidepressant effect via suppression of brain MAO activity.&#x0D; Keywords: Climacteric depression, Endocrine hormones, Menopause, Monoamine oxidase, Polyphenols

Comparison of the Effects of Deep Brain Stimulation of the Prelimbic Cortex and Basolateral Amygdala for Facilitation of Extinction Process of Conditioned Fear

Background: The study of the biological basis of fear in animal models has progressed considerably because of the energy and space that the brain devotes to this basic emotion. Electrical stimulation targets several structures of the brain to examine its behavioral effects and to understand the role of different regions in underlying mechanisms of fear processing and anxiety in preclinical models. Objectives: In this study, the effects of high-frequency deep brain stimulation (DBS) of the basolateral amygdala (BLA) and prelimbic (PL) sub-region of the prefrontal cortex were evaluated on the extinction process of conditioned fear. Methods: This study was performed on 35 male Wistar rats in the weight range of 220 – 250 g. After selecting the animals, they were separated into five groups. Then, we did stereotactic surgery on rats for electrode implantation. After recovery, some rats were conditioned, followed by a 10-day treatment schedule via high-frequency DBS in the BLA or PL. Next, freezing behavior was measured as a predicted response dedicated to extinction, without shock (re-exposure). In addition, we used ELISA and Western blot to estimate blood serum corticosterone levels and c-Fos protein expression. Results: The mean freezing time recorded for the PL group was significantly lower than that of both the BLA group and the PC group (P &lt; 0.01). The BLA group and PC group were also significantly different (P &lt; 0.001). Corticosterone results indicated that the PL group had significantly higher serum corticosterone levels compared with both the BLA group and the PC group (P &lt; 0.01). In addition, the BLA group revealed a significant reduction in c-Fos expression compared with the PC (P &lt; 0.001). Conclusions: This study provides further evidence for the contribution of the prelimbic cortex and amygdala both in acquisition and extinction processes during contextual fear conditioning. However, the PL stimulation by high-frequency DBS might be more involved in the extinction process and play a more important role as an enhancer.

Repeated and single maternal separation specifically alter microglial morphology in the prefrontal cortex and neurogenesis in the hippocampus of 15-day-old male mice.

Early-life adversity impairs neuronal plasticity of the developing brain. In rodents, brain maturation processes, including neuro- and synaptogenesis, myelination, microglial maturation, and hypothalamic-pituitary-adrenal (HPA) axis development continue in the postnatal period. In our study, two models of early-life stress were used: repeated maternal separation (MS) from postnatal day (PND) 2 to PND14 for 3 h daily and single maternal deprivation (MD) on PND9 for 24 h. Effects of each type of early-life stress on neuron density, neurogenesis, microglial morphology, and HPA axis programming were studied in 15-day-old male mice. Neither early-life stress paradigm affected the expression of stress-related genes (Crh, Avp, Crhr1, Crhr2, Nr3c1, and Nr3c2) and the serum level of corticosterone on PND15. Immunohistochemical analysis was performed on slices of the hippocampus and prefrontal cortex (PFC) with antibodies against a marker of mature neurons (NeuN), of microglia (Iba1), proliferating cells (Ki67), and immature neurons (DCX). We found higher density of ameboid microglia and intermediate microglia in the PFC in groups MS and MD, respectively, than in a control group. In both stressed groups, a higher number of Ki67-positive cells was noted in the dentate gyrus. Thus, in mice, the process of transformation of ameboid microglia into ramified ones as well as a neurogenesis reduction take place during the second postnatal week, whereas early-life stress can disturb these processes in a stress- and region-dependent manner.