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Grounding, a therapeutic technique involving direct contact with the earth, has been proposed by various studies to potentially have beneficial effects on pressure, sleep quality, stress, inflammation, and mood. However, the scientific evidence supporting its sedative effects remains incomplete. This study examined the sedative effectiveness of an earthing mat on sleep quality and investigated the underlying neural mechanisms using electroencephalography (EEG) analysis in rodents, focusing on orexin and superoxide dismutase (SOD) levels in the brain. Rats were randomly assigned to four groups: the naïve normal group (Nor), the group exposed to an earthing mat for 7 days (A-7D), the group exposed to an earthing mat for 21 days (A-21D), and the group exposed to an electronic blanket for 21 days (EM). EEG results revealed that the A-21D group exhibited significantly reduced wake time and increased rapid eye movement (REM), non-rapid eye movement (NREM), and total sleep time compared to the Nor group (p < 0.05). Moreover, the A-21D group demonstrated a significant increase in NREM sleep (p < 0.001), REM sleep (p < 0.01), and total sleep time (p < 0.001), along with a decrease in wake time compared to the EM group (p < 0.001). The orexin level in the A-21D group was significantly lower compared to the Nor group (p < 0.01), while SOD1 expression was markedly elevated in the A-21D group compared to the Nor group (p < 0.001). These results suggest that the earthing mat may represent a promising new method for promoting sleep quality and could serve as an effective therapeutic technique. [ABSTRACT FROM AUTHOR]

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders. [ABSTRACT FROM AUTHOR]

Grounding is a therapeutic technique that involves doing activities that "ground" or electrically reconnect us to the earth. The physiological effects of grounding have been reported from a variety of perspectives such as sleep or pain. However, its anti-stress efficacy is relatively unknown. The present study investigated the stress-related behavioral effects of earthing mat and its neurohormonal mechanisms in the Sprague–Dawley male rat. Rats were randomly divided into four groups: the naïve normal (Normal), the 21 days immobilization stressed (Control), the 21 days stressed + earthing mat for 7 days (A7) or 21 days (A21) group. The depressive-and anxiety like behaviors were measured by forced swimming test (FST), tail suspension test (TST) and elevated plus maze (EPM). Using immunohistochemistry, the expression of corticotrophin-releasing factor (CRF) and c-Fos immunoreactivity were analyzed in the brain. In the EPM, time spent in the open arm of the earthing mat groups was significantly increased compared to the Control group (p < 0.001), even though there were without effects among groups in the FST and TST. The expression of CRF immunoreactive neurons in the earthing mat group was markedly decreased compared to the Control group. Overall, the earthing mat reduced stress-induced behavioral changes and expression of c-Fos and CRF immunoreactivity in the brain. These results suggest that the earthing mat may have the potential to improve stress-related responses via the regulation of the corticotrophinergic system. [ABSTRACT FROM AUTHOR]

Background: Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice.Methods: CD4+CD25+ Tregs were expanded in vitro and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after killing the mouse. To investigate the neuroinflammatory responses, the polarization status of microglia was examined in vivo and in vitro using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assay (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging in vitro with an activation-specific fluorescence probe, CDr20.Results: Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via in vitro live time-lapse imaging in a Treg/microglia co-culture system.Conclusions: These data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization. [ABSTRACT FROM AUTHOR]

Many plants have been used in Korean medicine for treating insomnia. However, scientific evidence for their sedative activity has not been fully investigated. Thus, this study was carried out to investigate the sedative effects of the extracts of medicinal plants, including Yukmijihwang-tang and its various modified forms through the 5-HT2c receptor binding assay, and to further confirm its sleep-promoting effects and the underlying neural mechanism in rats utilizing electroencephalography (EEG) analysis. Enzyme-linked immunosorbent assay (ELISA) was used to measure serotonin (5-HT) in the brain. The water extracts of modified Yukmijihwang-tang (YmP) displayed binding affinity to the 5-HT2C receptor (IC50 value of 199.9 µg/mL). YmP (50 mg/kg) administration decreased wake time and increased REM and NREM sleep based on EEG data in rats. Additionally, treatment with YmP significantly increased the 5-HT level in the hypothalamus. In conclusion, the sedative effect of YmP can be attributed to the activation of the central serotonergic systems, as evidenced by the high affinity of binding of the 5-HT2C receptor and increased 5-HT levels in the brain of the rat. This study suggests that YmP can be a new material as a sleep inducer in natural products. [ABSTRACT FROM AUTHOR]

Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative–hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative–hypnotic effects of water extracts of five medicinal plants: Coptidis Rhizoma, Lycii Fructus, Angelicae sinensis Radix, Bupleuri Radix, and Polygonum multiflorum Thunberg. The binding abilities of five medicinal plant extracts to the GABAA–BZD and 5-HT2C receptors were compared. Their abilities to activate arylalkylamine N-acetyltransferase (AANAT), a melatonin synthesis enzyme, in pineal cells were also determined. Following in vitro tests, the sedative and hypnotic activities of extracts with the highest activities were determined in an animal sleep model. In the binding assay, the water extracts of Coptidis Rhizoma (WCR) showed high binding affinity to the GABAA–BZD and 5-HT2C receptors in a dose-dependent manner. Additionally, WCR increased the AANAT activity up to five times compared with the baseline level. Further animal sleep model experiments showed that WCR potentiated pentobarbital-induced sleep by prolonging the sleep time. It also decreased the sleep onset time in mice. In addition, WCR reduced wake time and increased non-rapid eye movement (NREM) sleep without EEG power density (percentages of δ, θ, and α waves) during NREM sleep in rats. WCR could effectively induce NREM sleep without altering the architectural physiologic profile of sleep. This is the first report of the sedative–hypnotic effect of Coptidis Rhizoma possibly by regulating GABAA and 5-HT2C receptors and by activating AANAT activity. [ABSTRACT FROM AUTHOR]

Berberine (BBR), a natural plant product, has been shown to have antidiabetic, cholesterol-reducing effects. To investigate the action of BBR as appetite suppressants, two experimental protocols were performed. In the first experiment, the mice were fed either a normal-chow diet or a high-fat diet (HF). The mice received daily intraperitoneal injections of BBR (10 mg/kg or saline at 1 ml/kg) for 3 weeks. To determine the antiobesity effects of BBR, the food consumption, body weight, fat contents, serum leptin, and glucose level were investigated. In the second experiment, we set out to validate the effect of BBR on central neuropeptide Y (NPY) stimulated rats. Experiments were carried out in 24-hour fasted rats, and then food intake and glucose level were subsequently recorded for 1 hour. The experimental groups were subdivided into the intra-3rd ventricular microinjections of ACSF (artificial cerebrospinal fluid), neuropeptide Y (NPY; 100 nM), NPY+BBR (10 nM), and NPY+BBR (100 nM) group. And then the blood glucose level was examined. In the first experiment, treatment with BBR in the HF diet mice reduced food intake, body weight, fat contents, serum leptin, and glucose level. In the second experiment, the NPY-injected group increased food intake by 39.3%, and food intake was reduced in the BBR group by 47.5%, compared with the ACSF-injected group. Also, the serum glucose level in the NPY+BBR (100 nM) group was significantly lower than that in the NPY (100 nM) group. The results suggest that BBR improved lipid dysregulation in obesity by controlling the central obesity related pathway. [ABSTRACT FROM AUTHOR]

Berberine (BBR), a natural plant product, has been shown to have antidiabetic, cholesterol-reducing effects. To investigate the action of BBR as appetite suppressants, two experimental protocols were performed. In the first experiment, the mice were fed either a normal-chow diet or a high-fat diet (HF). The mice received daily intraperitoneal injections of BBR (10 mg/kg or saline at 1 ml/kg) for 3 weeks. To determine the antiobesity effects of BBR, the food consumption, body weight, fat contents, serum leptin, and glucose level were investigated. In the second experiment, we set out to validate the effect of BBR on central neuropeptide Y (NPY) stimulated rats. Experiments were carried out in 24-hour fasted rats, and then food intake and glucose level were subsequently recorded for 1 hour. The experimental groups were subdivided into the intra-3rd ventricular microinjections of ACSF (artificial cerebrospinal fluid), neuropeptide Y (NPY; 100 nM), NPY+BBR (10 nM), and NPY+BBR (100 nM) group. And then the blood glucose level was examined. In the first experiment, treatment with BBR in the HF diet mice reduced food intake, body weight, fat contents, serum leptin, and glucose level. In the second experiment, the NPY-injected group increased food intake by 39.3%, and food intake was reduced in the BBR group by 47.5%, compared with the ACSF-injected group. Also, the serum glucose level in the NPY+BBR (100 nM) group was significantly lower than that in the NPY (100 nM) group. The results suggest that BBR improved lipid dysregulation in obesity by controlling the central obesity related pathway. [ABSTRACT FROM AUTHOR]

Menopause is a risk factor of anxiety and depression. Also, psychoneurological symptoms are shown in almost all women in the perimenopausal period. The present study investigated if repeated stress modulates behavioral changes or the balance of pro- and anti-inflammatory cytokines in ovariectomized (OVX) rats. Albino SD female rats were randomly divided into four groups: the naïve normal group (NOR), a surgically ovariectomized group (OVX), the only stressed group (ST), and the OVX and stressed groups (OVX + ST). We performed a battery of tests such as the forced swimming test (FST), the sucrose intake, and social exploration. In the same animals, corticosterone (CORT) was assessed in the serum, and also, two representative cytokines (IL-1β and IL-4) were examined in different brain regions after all the behavior sessions for all the experimental groups. The OVX + ST group showed more immobility time in FST than the OVX group or the ST group. Also, the OVX + ST group tended to have a decreased active social exploration and sucrose solution intake compared to the OVX group or ST group. The serum concentration of CORT of the OVX + ST group was higher than the OVX group or ST group and also the level of CORT in OVX + ST was markedly increased compared to the NOR group. In the brain, the number of IL-1β immunoreactive neurons of the OVX + ST group was increased compared to the NOR group. The OVX + ST group tended to have an increase in IL-1β-positive neurons compared to the OVX or ST group. However, the number of IL-4 immunoreactive neurons of the OVX + ST group was markedly decreased compared with the NOR group. Also, the IL-4-positive neurons in the OVX + ST group was significantly decreased when compared to the ST group. These results indicate that ovariectomy and stress combine to increase the depressive-like behaviors and neuroinflammatory responses. Together, these data show neuroinflammation as a potential contributor to depressive-like symptoms during menopausal transition. [ABSTRACT FROM AUTHOR]

Acer tegmentosum (ATM) has antioxidant and anti-adipogenic activity. However, few studies have investigated the pharmacological activity or mechanism of ATM as an antidepressant agent. We assessed the antidepressant effect of ATM in modulating menopausal depressive symptoms and its mechanisms in ovariectomized (OVX) and repeatedly stressed (RS) female rats. The female rats were randomly divided into four groups: (1) naïve normal (normal) group, (2) OVX + repeated stress + saline-treated (control) group, (3) OVX + repeated stress + ATM (100 mg•kg−1)-treated (ATM100) group and (4) OVX + repeated stress + ATM (400 mg•kg−1)-treated (ATM400) group. We performed a battery of tests, such as the forced swimming test (FST), the sucrose intake test, and social exploration. After behavior testing, serum corticosterone levels were examined, followed by immunohistochemical determination of c-Fos, tyrosine hydroxylase (TH), and interleukin-1 beta (IL-1β) expression in the brain. ATM administration was associated with significantly decreased immobility time in the FST. Also, the control group tended to have decreased sucrose intake and social exploration compared with the normal group. However, ATM treatment was associated with markedly increased sucrose intake and active social exploration. In the paraventricular nucleus, c-Fos and IL-1β expression were significantly decreased in the ATM400 group compared with the control group. Compared with the control group, high-dose ATM administration was also associated with markedly decreased expression of TH-immunoreactive neurons in the locus coeruleus. The study findings demonstrated that ATM treatment effectively decreased behavioral and pathophysiological depression-like responses. [ABSTRACT FROM AUTHOR]

Recently, neuroinflammation is thought to be one of the important causes of many neuropsychiatric diseases. Quercetin (QUER) is a natural flavonoid, and it is well known that QUER has antioxidative, anti-inflammatory, and neuroprotective effects. In our study, lipopolysaccharide (LPS) was injected into the lateral ventricle of rats to induce anxiety-like behaviors and neuroinflammation, and it was confirmed that chronic administration of QUER could improve anxiety-like symptoms. We also investigated the effects of QUER on inflammatory markers and its major mechanisms associated with inflammation in the hippocampus. Daily administration of QUER (10, 50, and 100 mg/kg) daily for 21 days significantly improved anxiety-like behaviors in the elevated plus-maze test and open field test. QUER administration significantly reduced inflammatory markers such as interleukin-6, interleukin-1β, cyclooxygenase-2, and nuclear factor-kappaB levels in the brain. In addition, QUER significantly increased the brain-derived neurotrophic factor (BDNF) mRNA level and decreased the nitric oxide synthase (iNOS) mRNA level. Therefore, our results have shown that QUER can improve anxiety-like behaviors caused by chronic neuroinflammation. This anxiolytic effect of QUER has been shown to be due to its anti-inflammatory effects and appropriate regulation of BDNF and iNOS expression. Thus, QUER provides the potential as a therapeutic agent to inhibit anxiety-like symptoms in neuropsychiatric diseases, such as anxiety. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a debilitating psychological disease that is triggered by traumatic events. It is known to cause various complications, including anxiety and depression. Umbelliferone (UMB) is a natural product of the coumarin family. This substance has been reported to exert antioxidant, anti-inflammatory, neuroprotective, and other biological effects. We used the open field test (OFT) and the forced swimming test (FST) to examine the effects of UMB on depression-like symptoms in rats after exposure to a single prolonged stress (SPS), which led to dysregulated activation of the serotonergic system. Male rats were given UMB (20, 40, or 60 mg/kg, intraperitoneal injection) once daily for 14 days after exposure to an SPS. Daily UMB administration significantly improved depression-like behaviors on the FST, increased the number of lines crossed in the central zone of the OFT, and reduced freezing behavior in both contextual and cued fear conditioning. UMB treatment attenuated the SPS-induced decrease in serotonin (5-HT) concentrations in the hippocampus and amygdala. The increased 5-HT concentration during UMB treatment was partially due to a decrease in the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus of rats with PTSD. According to our results, UMB has an antidepressant effect in rats exposed to an SPS, suggesting that this natural product of the coumarin family can be used to effectively treat PTSD. [ABSTRACT FROM AUTHOR]

Background: This study was designed to examine the effectiveness of program combining chakrayoga and meditation on the physical health and disease-related factors and psychological factors of people. Methods: Ninety-seven subjects (32–83 years old) who had free from prior experiences in meditation programs or Chakrayoga training courses were assigned to either the experimental group (EXP) (45 subjects; 13 male subjects and 32 female subjects; average age of 60.67 years, SD=11.09 years) or the control group (CONT) of remaining subjects (52 subjects; 14 male subjects and 38 female subjects; average age of 61.58 years, SD=9.70 years). Subjects in the EXP participated in the Chakrayoga Meditation Program for twice a week for 2 h during 6 weeks in each session consisted of 1 h of Chakrayoga and 1 h of meditation. The measurements in this study included the mindfulness, stress response, subjective quality of life, medical symptom checklist, difficulty in emotional regulation and objective of life and sense of control. Results: Results revealed that participants in the EXP reported significantly more relief of mindfulness, stress response, subjective quality of life and medical symptom checklist than those in the CONT. Conclusions: These findings provide evidence that the Chakrayoga Meditation Program can help relieve the physical health and disease-related factors and psychological factors. [ABSTRACT FROM AUTHOR]

Objective: To examine the anti-obesity effects of ginsenosides in Korea Red Ginseng (KRG, Panax ginseng) in rats fed with a high-fat diet (HFD). Methods: Twenty-five 4-week-old obesity rats after receiving an HFD for 5 weeks; subsequently, they were additionally treated with ginsenosides Rb1, Rd, Rg1, or Re (10 mg/kg, intraperitoneal injection) for a further 3 weeks (n=5 in each group). The control rats were fed a normal diet. The food consumption, body weight, locomotor activity, serum lipids, adipose tissues, nitric oxide (NO) expression, leptin, neuropeptide Y (NPY), cholecystokinin (CCK) in the brains were measured. Results: In the HFD-fed rats, body weight, body fat mass, serum levels of leptin and NO were significantly higher than in the control rats (P<0.05 or P<0.01). However, the treatment of Rd, Re, and Rb1 markedly decreased body fat mass and body weight (P<0.05). The serum level of leptin and NO in ginsenoside-treated rats were markedly lower than the control group (P<0.01). The expression of NPY and CCK in the hypothalamic nuclei showed insignificant difference among groups. However, the expression of NPY immunoreactive neurons in the hypothalamus was significantly reduced in the Rb1-treated group (P<0.05). Conclusion: PD-type ginsenoside Rb1 from the crude saponins of KRG may be a useful compound for the treatment of obesity and related disorders through the modulation of peripheral and central appetite-regulating signals. [ABSTRACT FROM AUTHOR]

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression. [ABSTRACT FROM AUTHOR]

Background. Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. Methods. All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. Results. Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. Conclusion. These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas. [ABSTRACT FROM AUTHOR]

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic stress disorder (PTSD) is a disease associated with that the experience of traumatic stress. The traumatic experience results in the development of a prolonged stress response that causes impaired memory function and increased inflammation in the hippocampus. Currently, antidepressants are the only approved therapy for PTSD. However, the efficacy of antidepressants in the treatment of PTSD is marginal. The ethanol extract of Aralia continentalis (AC) is traditionally used in oriental medicine, and has been showed to possess pharmacological properties, including anti-inflammatory, anti-cancer, anti-atherosclerotic, and anti-diabetic effects. Nevertheless, the effects of AC on cognitive memory and its mechanism of action in PTSD remain unclear. Given the necessity of further treatment options for PTSD, we investigated the effect of AC on the spatial cognitive impairment caused by single prolonged stress (SPS) in a rat model of PTSD. Methods: Male rats were treated with various intraperitoneal (i.p.) doses of AC for 21 consecutive days after inducing chronic stress with the SPS procedure. Results: Cognitive impairment caused by SPS were inhibited after treatment with 100 mg/kg AC, as measured by the Morris water maze test and an object recognition test. Additionally, AC treatment significantly alleviated memory-related decreases in brain-derived neurotrophic factor (BDNF) mRNA and protein levels in the hippocampus. Our results suggest that AC significantly inhibited the cognitive deficits caused by SPS via increased expression of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6, in the rat brain. Conclusions: AC reversed the behavioral impairments and inflammation triggered by SPS-derived traumatic stress and should be further evaluated as a potential therapeutic drug for PTSD. [ABSTRACT FROM AUTHOR]

Neuroinflammation is considered a major factor in several neuropsychiatric disorders. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including antiinflammatory, antioxidative, and protective properties. The present study was performed to examine whether GPS shows anxiolytic-like effects in a model of chronic inflammation induced by injection of lipopolysaccharide (LPS) into the rat hippocampus. The effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Introduction of LPS into the lateral ventricle caused inflammatory reactions and anxiety-like symptoms in the rats. Daily treatment with GPS (25, 50, and 100 mg/kg) for 21 consecutive days significantly increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. Moreover, GPS administration significantly reduced the freezing response to contextual fear conditioning, and significantly decreased the levels of proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB), levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of Toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA levels. Taken together, these results suggest that GPS may have anxiolytic-like effects and may have novel therapeutic potential for anxiety-like behaviors caused by neuroinflammation. GPS may be useful for developing an agents for the treatment of neuropsychiatric disorders, such as anxiety, due to its antiinflammatory activities and the modulation of NF-κB/iNOS/TLR4/BDNF. [ABSTRACT FROM AUTHOR]

Prolonged exposure to stress can affect mood and cognition and lead to mood disorders. Research on stress-associated mood disorders is important in modern society as people are increasingly exposed to unavoidable stressors. We used a mouse model with 2 weeks of exposure to electric foot shock and restraint, to determine the effect of Fraxinus rhynchophylla Hance (FX) extract on chronic stress-induced depression. We measured the effect of FX extract using various physiological, behavioral, and biochemical measures. FX extract ameliorated chronic stress-induced body and relative liver weight loss and improved depressive-like behaviors in the open field and forced swim tests. In addition, plasma cortisol and serotonin levels in stress-induced mice following FX treatment were similar to normal mice, and the elevation of proinflammatory cytokines was prevented. Moreover, FX treatment increased the expression of phosphorylated cyclic adenosine-3′,5′-monophosphate response element-binding protein (pCREB)/brain-derived neurotrophic factor (BDNF). Further experiments confirmed the efficacy of FX extract by showing similar results using esculin and esculetin, compounds extracted from FX. Taken together, these results indicate that FX extract has an antidepressant effect on chronic stress-induced depression by associating signaling with neuroinflammation and neurogenesis. [ABSTRACT FROM AUTHOR]

Neuroinflammation is deliberated a major factor in various neurodegenerative diseases. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including anti-inflammatory, antioxidative, and protective properties. In the present study, whether GPS could improve cognitive dysfunction and chronic inflammation caused by injecting lipopolysaccharide (LPS) in the hippocampus was investigated. Effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Induction of LPS into the lateral ventricle caused inflammatory reactions and memory impairment on the rats. Every day treatment of GPS (25, 50, and 100 mg/kg) for 21 consecutive days attenuated spatial recognition, discrimination, and memory deficits. GPS treatment significantly decreased proinflammatory mediators such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappaB (NF-κB) levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of inducible nitric oxide synthase (iNOS) and toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA level. Collectively, these results showed that GPS may improve cognitive function and provide a potential therapy for memory impairment caused by neuroinflammation. Based on these, GPS may be effective in inhibiting the progress of neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and appropriate modulation of NF-κB/iNOS/TLR4/BDNF. [ABSTRACT FROM AUTHOR]

Background: Human placenta hydrolysate (hPH) has been utilized to improve menopausal, fatigue, liver function. Its high concentration of bioactive substances is known to produce including antioxidant, anti-inflammatory and anti-nociceptive activities. However, its mechanisms of stress-induced depression remain unknown. Methods: The present study examined the effect of hPH on stress-induced depressive behaviors and biochemical parameters in rats. hPH (0.02 ml, 0.2 ml or 1 ml/rat) was injected intravenously 30 min before the daily stress session in male Sprague-Dawley rats exposed to repeated immobilization stress (4 h/day for 7 days). The depressive-like behaviors of all groups were measured by elevated plus maze (EPM) and forced swimming test (FST). After the behavior tests, brain samples of all groups were collected for the analysis of glutathione peroxidase (GPx) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining. Results: Treatment with hPH produced a significant decrease of immobility time in the FST compared to the controls. Additionally, hPH treatment elicited a slightly decreasing trend in anxiety behavior on the EPM. Furthermore, hPH increased the level of GPx protein in the hippocampus, and decreased the expression of NADPH-d in the paraventricular nucleus (PVN). Conclusion: This study demonstrated that hPH has anti-stress effects via the regulation of nitric oxide (NO) synthase and antioxidant activity in the brain. These results suggest that hPH may be useful in the treatment of stress-related diseases such as chronic fatigue syndrome. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experiences. This psychopathological response to traumatic stressors induces anxiety in rats. Oleuropein (OLE), a major compound in olive leaves, reportedly possesses several pharmacological properties, including anti-cancer, anti-diabetic, and anti-atherosclerotic and neuropsychiatric activities. However, the anxiolytic-like effects of OLE and its mechanism of action in PTSD are unclear. The present study used several behavioral tests to examine the effects of OLE on symptoms of anxiety in rats after a single prolonged stress (SPS) exposure by inhibiting the hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats received OLE (10, 50 and 70 mg/kg, i.p., once daily) for 14 days after SPS exposure. Daily OLE (70 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index and grooming behavior in the EPM test, and increased the time spent and number of central zone crossings in the open field test. OLE also blocked the SPS-induced decrease in hippocampal serotonin and neuropeptide Y expression in hippocampus. These findings suggest that OLE has anxiolytic-like effects on behavioral and biochemical symptoms similar to those observed in patients with PTSD. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a stress-related psychiatric/mental condition. Tangeretin (TAN), a major polymethoxylated flavone of citrus plants, exhibits anti-inflammatory and neuroprotective activities. However, whether TAN leads to cognitive improvement in PTSD patients remains unclear. In the present study, we explored whether TAN improved cognitive impairment induced in rats by single prolonged stress (SPS episode mimicking PTSD induction) and determined whether TAN reversed reductions in dopamine (DA) and serotonin (5-HT) levels. Rats were intraperitoneally injected with TAN for 14 consecutive days after the SPS, which had induced cognitive deficits evident in the object recognition task and the Morris water maze test; the impairments were improved by TAN (100 mg/kg). TAN rescued the neurochemical abnormalities and the SPS-induced decreases in DA and 5-HT levels in the hippocampus and amygdala. These effects may be attributable in part to induction of hippocampal genes encoding tyrosine hydroxylase and tryptophan hydroxylase-1. Our results support the idea that rats with PTSD exhibit changes in DAergic and serotonergic transmission and in memory impairment. Thus, TAN mediated reversal of memory-related behavioral dysfunction associated with traumatic stress may be a useful therapeutic intervention in PTSD patients. [ABSTRACT FROM AUTHOR]

The supramammillary area (SUM) of the hypothalamus has wide spread connection with numerous brain structures. It is known that the SUM can control the frequency of the hippocampal theta rhythm, which plays a role in the cognitive functions of the hippocampal formation. In order to examine the role of the specific cells of the SUM in learning and memory, selective cholinergic neurotoxic or excitotoxic lesioned rats of the SUM were tested for spatial memory on the Morris water maze (MWM) test. After the behavior tests, the expression of acetylcholinesterase (AChE) in the hippocampus was studied using the immunohistochemistry. In the MWM test, both lesion of the SUM with 192 IgG-saporin or ibotenic acid produced the impairment of spatial learning and memory. The expression of AChE immunreactive neurons in the hippocampal CA3 region was decreased after injections of 192 IgG-saporin into the SUM. These findings suggest that cholinoceptive cells of the SUM area may play a critical role in the process of learning and memory. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. This psychopathological response to traumatic stressors induces learning and memory deficits in rats. Oleuropein (OLE), a major compound in olive leaves, has been reported to possess several pharmacological properties, including anti-cancer, anti-diabetic, anti-atherosclerotic and neuroprotective activities. However, the cognitive effects of OLE and its mechanism of action have remained unclear in PTSD. In this study, we examined whether OLE improved spatial cognitive impairment induced in rats following single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or various doses of OLE for 14 consecutive days after the SPS procedure. The SPS procedure resulted in cognitive impairment in the object recognition task and the Morris water maze test, which was reversed by OLE (100 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction analysis, the administration of OLE significantly alleviated memory-associated decreases in the levels of brain-derived neurotrophic factor and cAMP response element-binding protein and mRNA in the hippocampus. Together, these findings suggest that OLE attenuated SPS-induced cognitive impairment significantly by inhibiting the expression of pro-inflammatory mediators in the rat brain. Thus, OLE reversed several behavioral impairments triggered by the traumatic stress of SPS and might be a potential useful therapeutic intervention for PTSD. [ABSTRACT FROM AUTHOR]

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase (COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants (N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. This study investigated whether treatment with the herbal formula PM012 would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test and positron-emission tomography (PET) with 18 F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. The levels of the amyloid beta (Aβ) deposits in the hippocampus were evaluated by immunohistochemistry. Neurogenesis was assessed by quantitative labeling with the DNA marker bromodeoxyuridine (BrdU) and the newborn neuron marker doublecortin (DCX). PM012 treatment significantly ameliorated memory deficit in AD mice, as shown by shortened escape latencies and increased time spent in the target zone during probe tests. In addition, PM012 significantly decreased Aβ deposits, up-regulated the expression of brain-derived neurotrophic factor (BDNF), increased neurogenesis, and improved brain glucose metabolism in the 3xTg-AD mice. These results suggest that PM012 could be a promising treatment for AD. [ABSTRACT FROM AUTHOR]

Exposure to severe stress can lead to the development of neuropsychiatric disorders such as depression and post-traumatic stress disorder (PTSD) in at-risk individuals. Gastrodin (GAS), a primary constituent of an Oriental herbal medicine, has been shown to effectively treat various mood disorders. Thus, the present study aimed to determine whether GAS would ameliorate stress-associated depression-like behaviors in a rat model of single prolonged stress (SPS)-induced PTSD. Following the SPS procedure, rats received intraperitoneal administration of GAS (20, 50, or 100 mg/kg) once daily for 2 weeks. Subsequently, the rats performed the forced swimming test, and norepinephrine (NE) levels in the hippocampus were measured. Daily GAS (100 mg/kg) significantly reversed depression-like behaviors and restored SPS-induced increases in hippocampal NE concentrations as well as tyrosine hydroxylase expression in the locus coeruleus. Furthermore, the administration of GAS attenuated SPS-induced decreases in the hypothalamic expression of neuropeptide Y and the hippocampal mRNA expression of brain-derived neurotrophic factor. These findings indicate that GAS possesses antidepressant effects in the PTSD and may be an effective herbal preparation for the treatment of PTSD. [ABSTRACT FROM AUTHOR]

A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The use of salivary biomarkers in stress research is increasing, and the precision and accuracy with which researchers are able to measure these biomarkers have dramatically improved. Chronic psychosocial stress is often linked to the pathogenesis of cardiovascular disease (CVD). Salivary biomarkers represent a noninvasive biological method of characterizing the stress phenomenon that may help to more fully describe the mechanism by which stress contributes to the pathogenesis and outcomes of CVD. Objectives: We conducted a systematic review of 40 research articles to identify the salivary biomarkers researchers have most commonly used to help describe the biological impact of chronic psychosocial stress and explore its associations with CVD risk. We address strengths and weaknesses of specimen collection and measurement. Methods: We used PubMed, CINAHL, EBSCOhost, Web of Science, BIOSIS Previews, Biological Sciences (ProQuest), and Dissertations/Theses (ProQuest) to retrieve 387 initial articles. Once we applied our inclusion/exclusion criteria to specifically target adult human studies dealing with chronic stress rather than acute/laboratory-induced stress, 40 studies remained, which we synthesized using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Results: Cortisol was the biomarker used most frequently. Sources of psychosocial stress included job strain, low socioeconomic status, and environmental factors. Overall, psychosocial stress was associated with CVD risks such as vascular pathology (hypertension, blood pressure fluctuation, and carotid artery plaque) as well as metabolic factors such as abnormal blood glucose, dyslipidemia, and elevated cardiac enzymes. Conclusion: Diverse salivary biomarkers have been useful in stress research, particularly when linked to CVD risks. [ABSTRACT FROM AUTHOR]

Single prolonged stress (SPS), a rat model of post-traumatic stress disorder (PTSD), induces alterations in the hypothalamic-pituitary-adrenal axis. Korean red ginseng, whose major active component is ginsenoside Rb1 (GRb1), is one of the widely used traditional anxiolytics. However, the efficacy of GRb1 in alleviating PTSD-associated anxiety-like abnormalities has not been investigated. The present study used several behavioral tests to examine the effects of GRb1 on symptoms of anxiety in rats after SPS exposure and on the central noradrenergic system. Male Sprague-Dawley rats received GRb1 (10 or 30 mg/kg, i.p., once daily) during 14 days of SPS. Daily GRb1 (30 mg/kg) administration significantly increased the number and duration of open-arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, reduced grooming behaviors in the EPM test, and increased the total number of line crossings of an open field after SPS. The higher dose of GRb1 also blocked SPS-induced decreases in hypothalamic neuropeptide Y expression, increases in locus coeruleus tyrosine hydroxylase expression, and decreases in hippocampal mRNA expression of brain-derived neurotrophic factor. These findings suggest that GRb1 has anxiolytic-like effects on both behavioral and biochemical symptoms similar to those observed in patients with PTSD. [ABSTRACT FROM AUTHOR]

It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL-4 was reduced in response to IMO. It was observed that IMO groups were more anxious than nontreated groups. Acute IMO (2 h/day, once) stimulated secretion of plasma corticosterone and tyrosine hydroxylase (TH) in the LC whereas these increments were diminished in exposure to chronic stress (2 h/day, 21 consecutive days). Glucocorticoid receptor (GR), TH, and IL-4-expressing cells were localized in identical neurons of the LC, indicating that hypothalamic-pituitary-adrenal- (HPA-) axis and sympathetic-adrenal-medullary- (SAM-) axis might be involved in IL-4 secretion in the stress response. Accordingly, it was concluded that stress-induced decline of IL-4 concentration from LC neurons may be related to anxiety-like behavior and an inverse relationship exists between IL-4 secretion and HPA/SAM-axes activation. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a severe neuroinflammatory disease. CD4(+)Foxp3(+) regulatory T cells (Tregs) modulate various inflammatory diseases via suppressing Th cell activation. There are increasing evidences that Tregs have beneficial roles in neurodegenerative diseases. Previously, we found the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro.Methods: To examine the effects of bvPLA2 on AD, bvPLA2 was administered to 3xTg-AD mice, mouse model of Alzheimer's disease. The levels of amyloid beta (Aβ) deposits in the hippocampus, glucose metabolism in the brain, microglia activation, and CD4(+) T cell infiltration were analyzed to evaluate the neuroprotective effect of bvPLA2.Results: bvPLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of Aβ deposits in the hippocampus were dramatically decreased by bvPLA2 treatment. This neuroprotective effect of bvPLA2 was associated with microglial deactivation and reduction in CD4(+) T cell infiltration. Interestingly, the neuroprotective effects of bvPLA2 were abolished in Treg-depleted mice.Conclusions: The present studies strongly suggest that the increase of Treg population by bvPLA2 treatment might inhibit progression of AD in the 3xTg AD mice. [ABSTRACT FROM AUTHOR]

The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL–6, and IL–1β), iNOS, and chemokines (MCP–1, MIP–1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM–1 and VCAM–1), and junctional molecules (claudin–3, claudin–5, and zona occludens–1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL–17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis. [ABSTRACT FROM AUTHOR]

It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study. [ABSTRACT FROM AUTHOR]

Background: Repeated injection of corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. We examined the effects of Angelica gigas extract (AGN) treatment in a rat model of depressive and anxiety-like behaviors, induced by chronic CORT exposure. Methods: Male rats received 10, 20, or 50 mg/kg AGN (i.p.) 30 min prior to a daily injection of CORT for 21 consecutive days. Activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotropin-releasing factor in the hypothalamus. Results: Daily AGN administration significantly reversed the depression and anxiety-like behavioral abnormalities. It also blocked increases in tyrosine hydroxylase expression in the locus coeruleus, and suppressed the decreased expression levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB mRNAs in the hippocampus. Conclusions: These findings indicate that administration of AGN prior to high-dose exogenous CORT significantly improved helpless behaviors, possibly by modulating the central noradrenergic system and regulation of BDNF expression in rats. Thus, AGN may be a useful agent for the treatment or alleviation of psychiatric disorders associated with depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

Cancer related fatigue (CRF) is one of the most common side effects of cancer and its treatments. A large proportion of cancer patients experience cancer-related physical and central fatigue so new strategies are needed for treatment and improved survival of these patients. BST204 was prepared by incubating crude ginseng extract with ginsenoside-β-glucosidase. The purpose of the present study was to examine the effects of BST204, mixture of ginsenosides on 5-fluorouracil (5-FU)-induced CRF, the glycogen synthesis, and biochemical parameters in mice. The mice were randomly divided into the following groups: the naïve normal (normal), the HT-29 cell inoculated (xenograft), xenograft and 5-FU treated (control), xenograft + 5-FU + BST204-treated (100 and 200 mg/kg) (BST204), and xenograft + 5-FU + modafinil (13 mg/kg) treated group (modafinil). Running wheel activity and forced swimming test were used for evaluation of CRF. Muscle glycogen, serum inflammatory cytokines, aspartic aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), white blood cell (WBC), neutrophil (NEUT), red blood cell (RBC), and hemoglobin (HGB) were measured. Treatment with BST204 significantly increased the running wheel activity and forced swimming time compared to the control group. Consistent with the behavioral data, BST204 markedly increased muscle glycogen activity and concentrations of WBC, NEUT, RBC, and HGB. Also, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), AST, ALT, and CRE levels in the serum were significantly reduced in the BST204-treated group compared to the control group. This result suggests that BST204 may improve chemotherapy-related fatigue and adverse toxic side effects. [ABSTRACT FROM AUTHOR]

The pathophysiology underlying anxiety disorders involves stress and associated increases in glucocorticoid levels in the blood. The present study investigated the effects of the administration of the crude extract ofPolygala tenuifolia(EPT) on repeated restraint stress–induced anxiety-like behavioral responses in mice. Additionally, possible changes in the central noradrenergic and brain-derived neurotrophic factor (BDNF)–signaling systems were assessed in the hippocampus of these mice. For 14 consecutive days, mice were orally administrated EPT (50 or 250 mg/kg) 30 min prior to the restraint stress procedure (2 h/day). Dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis in response to the repeated restraint stress was confirmed by measuring serum levels of corticosterone and the expression of corticotrophin-releasing factor in the hypothalamus. Compared with control subjects, the daily administration of higher doses of EPT (250 mg/kg) increased open-arm exploration in an elevated plus maze and the total number of line crossings in an open-field test. EPT also reversed the increased expression of tyrosine hydroxylase in the locus coeruleus and the decreased expression of BDNF mRNA in the hippocampus. Together, these findings demonstrate that the administration of EPT prior to repeated restraint stress significantly reduced anxiety-like behaviors in mice. These changes were associated with a modification of the central noradrenergic system and the upregulation of BDNF expression, which in turn attenuated activity in the HPA axis. [ABSTRACT FROM PUBLISHER]

PM012 is a modified oriental medicinal prescription based on Yukmijihwang-tang.We previously reported that PM012 has a neuro-protective effect and has no toxicity with chronic administration in rats. As a process of the development of herbal new drug, we assessed the oral toxicity of PM012 in Beagle dogs. PM012 was administered orally for 28 days at doses of 0, 250, 500, 1000 and 1500 mg/kg/day. When we analyzed the body weight gain, food consumption, clinical observations, blood biochemical, hematology, organ weight ratios and histopathological findings, there were no significant differences between the control and treated groups. It was concluded that orally administered PM012 was safe in dogs, and no treatment-related toxicity was detected, even at the highest doses investigated in repeated dose oral toxicity studies. [ABSTRACT FROM AUTHOR]

We investigated the anxiolytic-like activity of a -asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety. [ABSTRACT FROM AUTHOR]

We examined whether a crude methanol extract ofAngelica gigas(AgMx) improved the spatial cognitive impairment induced by repeated immobilization (IMO) stress in rats. The effects of AgMx on hippocampal expression of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) were also investigated. For 21 days, male rats received daily doses of AgMx (20, 50, or 100 mg/kg, i.p.) 30 min prior to daily exposure to IMO stress (6 h/day). The daily administration of AgMx improved memory impairment, as measured by the passive avoidance test, and reduced the escape latency for finding the platform in the Morris water maze test. Additionally, as assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis, the administration of AgMx significantly alleviated memory-associated decreases in the expression levels of BDNF and CREB proteins and mRNAs in the hippocampus. Thus, these findings suggest that AgMx may be useful as a therapeutic agent in various neurodegenerative diseases for improving cognitive function. It effects likely involve the regulation of BDNF and CREB expressions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether baicalin (BAI) improves spatial cognitive impairments induced in rats following the repeated administration of the exogenous stress hormone corticosterone (CORT). The effect of BAI on the hippocampal expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) was also investigated. For 21 days, male rats received daily doses of BAI (20, 50, and 100 mg/kg, i.p.) 1 h prior to a CORT (40 mg/kg) injection. The daily administration of BAI improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Additionally, as assessed by immunohistochemistry and reverse transcription–polymerase chain reaction (RT-PCR) analysis, the administration of BAI also significantly alleviated memory-associated decreases in the expression levels of BDNF and CREB proteins and mRNAs in the hippocampus. These results demonstrate that the administration of BAI prior to high-dose exogenous CORT results in significant neuroprotective activity against neuronal impairment and memory dysfunction in rats. Thus, these findings suggest that BAI might be useful as a therapeutic agent in various neurodegenerative diseases for the improvement of cognitive function. This likely occurs through the regulation of BDNF and CREB expression. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that repeated restraint stress in rodents increased depression-like behavior and altered the expression of corticotrophin-releasing factor in the hypothalamus. The current study focused on verifying the impact of fucoidan (FCN) administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST). Additionally, we examined the effect of FCN on the central noradrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brains. Male rats received 10, 20, or 50 mg/kg FCN (i.p.) 30 min before daily exposures to repeated restraint stress (2 h/day) for 14 days. Repeated restraint stress increased immobility in the FST. Daily administration of FCN during the repeated restraint stress period significantly inhibited the stress-induced behavioral deficits in this behavioral test. Administration of FCN also significantly blocked the increase in TH expression in the locus coeruleus and the basolateral nucleus of the amygdala, and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of FCN prior to restraint stress significantly improved helpless behavior in rats, possibly through modulating the central noradrenergic system. Therefore, FCN may be a useful agent for treating complex symptoms of depression disorder. [ABSTRACT FROM AUTHOR]

Objective: Phosphatidylserine, a major acidic phospholipid in the brain, has been studied extensively in regard to its actions on brain functions. The present study examined the effects of Krill phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in the normal young rats. Methods: The rats were administered saline or Krill-PS (Krill-PS 50, 100 mg/kg, per oral) daily for 30 days. The cognitive improvement effect of Krill-PS on the normal young rats was investigated by assessing the Morris water maze (MWM) test and by insulin-like growth factor (IGF) and brain-derived neurotrophic factor (BDNF) immunohistochemistry. A positron emission tomography (PET) scan was also performed. Results: Treatment with Krill-PS (100 mg/kg) produced a significant improvement of the escape latency to find the platform in the MWM at the 3rd day compared to that of the normal group. In the retention test, the Krill-PS100 group showed markedly increased time spent, distance, and crossing number around the platform compared to that of the normal group. Consistent with the behavioral data, the Krill-PS 100 group was significantly enhanced the BDNF and IGF immuno-positive neurons in the hippocampal CA1. In the PET analysis, the glucose uptake of the Krill-PS-treated groups was increased in the frontal lobe and hippocampus. These results suggest that repeated Krill-PS treatment may be useful for improving the cognitive function via regulation of neuronal growth factor activity. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain. [ABSTRACT FROM AUTHOR]