Serotonergic system may be involved in alterations of sleep homeostasis in spontaneously hypertensive rats.

Hypertension is associated with sleep disorders. Spontaneously hypertensive rats are derived from Wistar-Kyoto rats and widely used in research on hypertension. The present study investigated the propensity to sleep and electroencephalographic spectrum changes over 24 hr in spontaneously hypertensive rats, and proposed the involvement of the serotonergic system in these alterations. Time-course analysis showed that spontaneously hypertensive rats exhibit hyperarousal during the light phase but hypersomnia during the dark phase. Spontaneously hypertensive rats also exhibited less slight fluctuation in electroencephalographic delta power density over 24 hr as compared with Wistar-Kyoto rats, suggesting that the accumulation or elimination of sleep pressure was disrupted. Sleep deprivation disrupted the regulation of sleep homeostasis in spontaneously hypertensive rats, reflected by less sleep time and poor sleep quality during the recovery period. The density and activity of serotonergic neurons in the dorsal raphe nucleus were higher in spontaneously hypertensive rats compared with Wistar-Kyoto rats. Interestingly, we observed the absence of fluctuations in 5-hydroxytryptamine and 5-hydroxyindoleacetic acid across the sleep, wake, sleep deprivation and sleep recovery stages in spontaneously hypertensive rats, which were dramatically different from Wistar-Kyoto rats. These results indicate that the disruption of sleep-wake pattern and sleep homeostasis in spontaneously hypertensive rats might be related to abnormalities of the serotonergic system.

Melanin-Concentrating Hormone (MCH) and MCH-R1 in the Locus Coeruleus May Be Involved in the Regulation of Depressive-Like Behavior.

Background: Previous anatomical and behavioral studies have shown that melanin-concentrating hormone is involved in the modulation of emotional states. However, little is known about brain regions other than the dorsal raphe nucleus that relate the melanin-concentrating hormone-ergic system to depressive states. Numerous studies have shown that the locus coeruleus is involved in the regulation of depression and sleep. Although direct physiological evidence is lacking, previous studies suggest that melanin-concentrating hormone release in the locus coeruleus decreases neuronal discharge. However, remaining unclear is whether the melanin-concentrating hormone-ergic system in the locus coeruleus is related to depressive-like behavior. Method: We treated rats with an intra-locus coeruleus injection of melanin-concentrating hormone, intracerebroventricular injection of melanin-concentrating hormone, or chronic subcutaneous injections of corticosterone to induce different depressive-like phenotypes. We then assessed the effects of the melanin-concentrating hormone receptor 1 antagonist SNAP-94847 on depressive-like behavior in the forced swim test and the sucrose preference test. Results: The intra-locus coeruleus and intracerebroventricular injections of melanin-concentrating hormone and chronic injections of corticosterone increased immobility time in the forced swim test and decreased sucrose preference in the sucrose preference test. All these depressive-like behaviors were reversed by an intra-locus coeruleus microinjection of SNAP-94847. Conclusions: These results suggest that the melanin-concentrating hormone-ergic system in the locus coeruleus might play an important role in the regulation of depressive-like behavior.

Dysfunction of GABAergic neurons in the parafacial zone mediates sleep disturbances in a streptozotocin-induced rat model of sporadic Alzheimer's disease.

Sleep disturbances are prevalent among patients with Alzheimer's disease (AD) and often precede the onset and progression of dementia. However, there are no reliable animal models for investigating sleep disturbances in patients with sporadic AD (sAD), which accounts for more than 90% of all AD cases. In the present study, we characterize the sleep/wake cycles and explore a potential mechanism underlying sleep disturbance in a rat model of sAD induced via intracerebroventricular (icv) injection of streptozotocin (STZ). STZ-icv rats exhibited progressive decreases in slow wave sleep (SWS) during the light phase and throughout the light/dark cycle beginning from 7 days after STZ-icv. Additionally, increased wakefulness and decreased rapid-eye-movement (REM) and non-REM (NREM) sleep were observed from 14 days after STZ-icv. Beginning on day 7, STZ-icv rats exhibited significant decreases in delta (0.5-4.0 Hz) power accompanied by increased power in the beta (12-30 Hz) and low gamma bands (30-50 Hz) during NREM sleep, resembling deficits in sleep quality observed in patients with AD. Immunohistochemical staining revealed a significant reduction in the ratio of c-Fos-positive GABAergic neurons in the parafacial zone (PZ) beginning from day 7 after STZ-icv. These results suggest that the STZ-icv rat model is useful for evaluating sleep disturbances associated with AD, and implicate the dysregulation of GABAergic neuronal activity in the PZ is associated with sleep disturbance induced by STZ.

Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation.

Mechanisms Underlying Footshock and Psychological Stress-Induced Abrupt Awakening From Posttraumatic "Nightmares".

BACKGROUND: Posttraumatic nightmares are a highly prevalent and distressing symptom of posttraumatic stress disorder (PTSD), but have been the subject of limited phenomenological investigations. METHODS: We utilized a communication box to establish PTSD symptoms in rats through exposure to footshock stress (FS) and psychological stress (PS). The immunohistochemical test and high-performance liquid chromatography with electrochemical detection were used to detect the activity and monoamine levels in the rats' arousal systems. RESULTS: Twenty-one days after traumatic stress, 14.17% of FS and 12.5% of PS rats exhibited startled awakening, and the same rats showed hyperfunction of the locus coeruleus/noradrenergic system and hypofunction of the perifornical nucleus/orexinergic system. Changes in serotonin levels in the dorsal raphe nucleus showed opposite trends in the FS and PS rats that were startled awake. No differences were found in other sleep/arousal systems. CONCLUSION: These results suggest that different clinically therapeutic strategies should be considered to treat different trauma-induced posttraumatic nightmares.

Involvement of adrenoceptors, dopamine receptors and AMPA receptors in antidepressant-like action of 7-O-ethylfangchinoline in mice.

AIM: 7-O-ethylfangchinoline (YH-200) is a bisbenzylisoquinoline derivative. The aim of this study was to investigate the antidepressant-like action and underlying mechanisms of YH-200 in mice. METHODS: Mice were treated with YH-200 (15, 30, and 60 mg/kg, ig) or tetrandrine (30 and 60 mg/kg, ig) before conducting forced swimming test (FST), tail suspension test (TST), or open field test (OFT). RESULTS: YH-200 (60 mg/kg) significantly decreased the immobility time in both FST and TST, and prolonged the latency to immobility in FST. YH-200 (60 mg/kg) was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine (60 mg/kg) in FST. Pretreatment with α1-adrenoceptor antagonist prazosin (1 mg/kg), ß-adrenoceptor antagonist propranolol (2 mg/kg), dopamine D1/D5 receptor antagonist SCH23390 (0.05 mg/kg), dopamine D2/D3 receptor antagonist haloperidol (0.2 mg/kg) or AMPA receptor antagonist NBQX (10 mg/kg) prevented the antidepressant-like action of YH-200 (60 mg/kg) in FST. In contrast, pretreatment with α2 adrenoceptor antagonist yohimbine (1 mg/kg) augmented the antidepressant-like action of YH-200 (30 mg/kg) in FST. Chronic administration of YH-200 (30 and 60 mg/kg for 14 d) did not produce drug tolerance; instead its antidepressant-like action was strengthened. Chronic administration of YH-200 did not affect the body weight of mice compared to control mice. CONCLUSION: YH-200 exerts its antidepressant-like action in mice via acting at multi-targets, including α1, α2 and ß-adrenoceptors, D1/D5 and D2 /D3 receptors, as well as AMPA receptors.

Correlations between depression behaviors and sleep parameters after repeated corticosterone injections in rats.

AIM: Disrupted sleep may be a prodromal symptom or a predictor of depressive disorders. In this study we investigated the relationship between depression symptoms and disrupted sleep using a novel model of stress-mimicked sleep disorders in rats. METHODS: SD rats were injected with corticosterone (10, 20 or 40 mg/kg, sc) or vehicle for 7 d. Their sleep-wake behavior was monitored through implanted EEG and EMG electrodes. Their depressive behaviors were assessed using forced swim test, open field test and sucrose preference test. RESULTS: The corticosterone-treated rats showed significantly reduced sleep time, disinhibition of rapid-eye-movement (REM) sleep and altered power spectra during non-REM sleep. All depressive behavioral tests did not show significant difference across the groups. However, individual correlation analysis revealed statistically significance: the immobility time (despair) was negatively correlated with REM sleep latency, slow wave sleep (SWS) time ratio, SWS bouts and delta power density, and it was positively correlated with REM sleep bouts and beta power density. Meanwhile, sucrose preference (anhedonia) was positively correlated with total sleep time and light sleep bouts, and it was negatively correlated with the REM sleep time ratio. CONCLUSION: In stress-mimicked rats, sleep disturbances are a predictor of depressive disorders, and certain symptoms of depression may be related to the disruption of several specific sleep parameters.

Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores. AIM OF THE STUDY: The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action. MATERIALS AND METHODS: In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid ß (Aß) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot. RESULTS: Treatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aß expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS. CONCLUSION: These findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aß expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.

Anti-stress effects of combined block of glucocorticoid and mineralocorticoid receptors in the paraventricular nucleus of the hypothalamus.

BACKGROUND AND PURPOSE: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviours. EXPERIMENTAL APPROACH: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive- and anxiety-like behaviours were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by western blot. KEY RESULTS: Rats exposed to corticosterone exhibited depressive- and anxiety-like behaviours. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviours. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety-like behaviours. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive- and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.

A common neuronal mechanism of hypertension and sleep disturbances in spontaneously hypertensive rats: Role of orexinergic neurons.

Epidemiologic studies have shown that sleep disorders are associated with the development of hypertension. The present study investigated dynamic changes in sleep patterns during the development of hypertension across the lifespan in spontaneously hypertensive rats (SHRs) and the neural mechanism that underlies these comorbidities, with a focus on the orexinergic system. Blood pressure in rats was measured using a noninvasive blood pressure tail cuff. Sleep was monitored by electroencephalographic and electromyographic recordings. Immunohistochemistry was used to detect the density and activity of orexinergic neurons in the perifornical nucleus. Hcrt2-SAP (400 or 800 ng) was microinjected in the lateral hypothalamus to lesion orexinergic neurons. Compared with Wistar-Kyoto rats, SHRs exhibited various patterns of sleep disturbances. In SHRs, dynamic changes in hypersomnia in the rats' active phase was not synchronized with the development of hypertension, but hyperarousal in the inactive phase and difficulties in falling asleep were observed concurrently with the development of hypertension. Furthermore, the density and activity of orexinergic neurons in the perifornical nucleus were significantly higher in SHRs than in age-matched Wistar-Kyoto rats. The reduction of orexinergic neurons in the lateral hypothalamus partially ameliorated the development of hypertension and prevented difficulties in falling asleep in SHRs. These results indicate that although the correlation between sleep disturbances and hypertension is very complex, common mechanisms may underlie these comorbidities in SHRs. Overactivity of the orexin system may be one such common mechanism.

Ginsenoside Rg1 promotes sleep in rats by modulating the noradrenergic system in the locus coeruleus and serotonergic system in the dorsal raphe nucleus.

Panax ginseng Mayer has been used as tranquilizer to improve sleep disorder, but its active component is not defined. This study investigated the effects of the most abundant constituents of P. ginseng-protopanaxatriol ginsenoside Rg1 and protopanaxadiol ginsenoside Rb1-on sleep in rats. Male Sprague-Dawley rats received intragastrical injections of Rg1 and Rb1 for 3 days (5, 10, and 20 mg/kg/day). Sleep parameters were analyzed using electroencephalogram and electromyogram. Neuronal activation and monoaminergic neurotransmitters were evaluated using immunohistochemical fluorescence staining and HPLC, respectively. Rg1 treatment significantly increased the duration of total sleep, rapid eye movement sleep (REMS) and Non-REMS at the dose of 5, 10 and 20 mg/kg/day, and also prolonged the proportion of slow-wave sleep in the total sleep. The Non-REMS episodes were increased and the mean duration of each wakefulness episode was depressed by Rg1 treatment. Rb1 had no effect on sleep parameters. Rg1 treatment decreased the activity of noradrenergic neurons in locus coeruleus (LC) and increased the activity of serotonergic neurons in the dorsal raphe nucleus (DRN). Besides, Rg1 depressed extracellular norepinephrine concentrations in both LC and DRN and in other sleep-regulating brain regions of which functions can be modulated by monoaminergic neurotransmitters discharged from projecting noradrenergic and serotonergic neurons. In conclusion, Rg1 might be the sleep-promoting component in P. ginseng and its mechanism may be related to the modulation of noradrenergic and serotonergic systems. Our findings also highlight functional differences between Rg1 and Rb1.

Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system.

Semen Zizhiphi Spinozae has been used extensively for the treatment of insomnia. This study investigated the effect and possible mechanism of action of spinosin (also known as 2''-beta-o-glucopyranosyl swertisin), a major constituent of semen Zizhiphi Spinozae, on sleep in mice. The present results showed that spinosin significantly and dose-dependently augmented pentobarbital (45 mg/kg, i.p.)-induced sleep, reflected by increased sleep time and reduced sleep latency assessed with the loss-of-righting reflex, and these effects were potentiated by the 5-hydroxytryptamine (serotonin) precursor 5-hydroxytryptophan (5-HTP, 2.5 mg/kg,i.p.). With a subhypnotic dose of pentobarbital (28 mg/kg, i.p.), spinosin significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleep time, and spinosin significantly reversed this effect. The dopamine precursor L-3-(3, 4-dihydroxyphenylalanine (L-DOPA) reduced pentobarbital-induced sleep, an effect not significantly affected by spinosin. These results suggest that spinosin potentiated pentobarbital-induced sleep via a serotonergic mechanism.

Depression-like behaviors induced by chronic corticosterone exposure via drinking water: Time-course analysis.

Hypothalamic-pituitary-adrenal (HPA) axis activity is commonly dysregulated in stress-related psychiatric disorders. The corticosterone rat model was developed to understand the influence of stress on depression-like symptomatology. To further understand the effects of corticosterone on the development of depression-like behavior, rats were continuously exposed to corticosterone (200 µg/ml) or vehicle via drinking water daily for 21 days. The rats underwent a series of behavioral tests, and electroencephalographical recordings were performed after 7, 14, and 21 days of treatment. The measurements included immobility time (i.e., despair) in the forced swim test, locomotor activity in the open field test, sucrose consumption (i.e., anhedonia) in the sucrose preference test, and sleep-wake parameters. The rats in the 7-day corticosterone exposure group exhibited depression-like behavior, including increases in despair, anhedonia, anxiety, and sleep impairments. The rats in the 14-day corticosterone exposure group exhibited normal patterns of behavior and sleep structure. When corticosterone exposure was extended to 21 days, depression-like symptoms recurred, including despair, anhedonia, anxiety, and sleep disturbances. Overall, the present study observed U-shaped depression-like effects across 3 weeks of corticosterone exposure via drinking water.

Intracerebroventricular streptozotocin-induced Alzheimer's disease-like sleep disorders in rats: Role of the GABAergic system in the parabrachial complex.

AIM: Sleep disorders are common in Alzheimer's disease (AD) and assumed to directly influence cognitive function and disease progression. This study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular streptozotocin (STZ) administration and assessed the possible underlying mechanisms. METHODS: Cognition ability was assessed in the Morris water maze in rats. Sleep parameters were analyzed by electroencephalographic and electromyographic recordings. Neuronal activity in brain areas that regulate sleep-wake states was evaluated by double-staining immunohistochemistry. High-performance liquid chromatography with electrochemical detection was used to detect neurotransmitter levels. RESULTS: Fourteen days after the STZ injection, the rats exhibited sleep disorders that were similar to those in AD patients, reflected by a significant increase in wakefulness and decreases in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ-injected rats. In the ventrolateral preoptic nucleus (VLPO), the activity of γ-aminobutyric acid (GABA) neurons was suppressed. In the arousal-driving parabrachial nucleus (PBN), GABAergic activity was suppressed, whereas glutamatergic activity was promoted. The neurotransmitter analysis revealed a reduction in GABA in the VLPO and PBN and elevation of glutamate in the PBN. A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar pattern of sleep disorder as in STZ-injected rats. A microinjection of GABA in the PBN improved sleep disorders that were induced by STZ. CONCLUSION: These results suggest that the reduction in GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders that are induced by STZ. Our novel findings encourage further studies that investigate mechanisms of sleep regulation in sporadic AD.

Sleep patterns deteriorate over time in chronic corticosterone-treated rats.

Repeated corticosterone (CORT) injections reliably produce depressive-like behavior in rodents. Our previous study showed that sleep parameters were altered in rats after daily injections of CORT for 7 days, and sleep disturbances appeared to be correlated with depressive-like behavior. The aim of the present study was to investigate time-dependent correlations between changes in sleep parameters and the formation of depressive-like behavior in rats after more prolonged treatment with CORT. Rats received daily injections of CORT (40 mg/kg, s.c.) for 7, 14, or 21 days. Electroencephalographic recordings were performed to study sleep parameters. The sucrose preference test and forced swim test were performed to evaluate depressive-like behavior. Western blot was used to detect protein levels. Our results showed that 7-day CORT treatment resulted in no significant depressive-like behavior or changes in rapid-eye-movement (REM) sleep. However, the duration of non-REM sleep significantly decreased, tyrosine hydroxylase (TH) levels significantly increased, and glucocorticoid receptor (GR) expression decreased in the locus coeruleus. Treatment with CORT for 14 and 21 days increased depressive-like behavior, enhanced REM sleep, shortened REM sleep latency, decreased TH and GR levels, and increased the levels of the chaperone FK506 binding protein 51 (FKBP51) in the locus coeruleus. These results indicate that the development of depression after chronic CORT treatment may be related to the formation of sleep disorders. Abnormalities of REM sleep may be a characteristic of sleep in models of depression that is induced by chronic CORT administration in rats. The noradrenergic system and GR pathway in the locus coeruleus may be involved in the formation of depression concomitant with sleep disturbances.

Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism.

Ganoderma lucidum has been used for the treatment of a variety of diseases. For the first time here we report a detailed study on the mechanisms and effects of G. lucidum aqueous extract (GLE) on sleep and its sedative activity. GLE showed no effects on sleep architecture in normal rats at doses of 80 and 120 mg/kg. However, GLE significantly decreased sleep latency, increased sleeping time, non-REM sleep time and light sleep time in pentobarbital-treated rats. Suppression of locomotor activity in normal mice induced by GLE was also observed. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3.5 mg/kg showed a significant antagonistic effect on the shortening in sleep latency, increase in sleeping time, non-REM sleep time or light sleep time in pentobarbital-treated rat induced by GLE. Significant effect was also observed with GLE on delta activity during non-REM sleep and flumazenil did not block this effect. In conclusion, GLE may be a herb having benzodiazepine-like hypnotic activity at least in part.

Electricity production and microbial characterization of thermophilic microbial fuel cells.

Thermophilic microbial fuel cell (TMFC) offers many benefits, but the investigations on the diversity of exoelectrogenic bacteria are scarce. In this study, a two-chamber TMFC was constructed using ethanol as an electron donor, and the microbial dynamics were analyzed by high-throughput sequencing and 16S rRNA clone-library sequencing. The open-circuit potential of TMFC was approximately 650mV, while the maximum voltage was around 550mV. The maximum power density was 437mW/m2, and the columbic efficiency in this work was 20.5±6.0%. The Firmicutes bacteria, related to the uncultured bacterium clone A55_D21_H_B_C01 with a similarity of 99%, accounted for 90.9% of all bacteria in the TMFC biofilm. This unknown bacterium has the potential to become a new thermophilic exoelectrogenic bacterium that is yet to be cultured. The development of TMFC-involved biotechnologies will be beneficial for the production of valuable chemicals and generation of energy in the future.

Antioxidative and acute anti-inflammatory effects of Campsis grandiflora flower.

The present study was undertaken to investigate the antioxidative and anti-inflammatory activities of the extract of the flower of Campsis grandiflora (Thunb.) K. Schum. Exposure of human dermal fibroblasts to 50% EtOH extract of Campsis grandiflora flower (ECG) at 10 and 100 microg/ml showed significant protective effect against hydrogen peroxide (300 microM). ECG not only protected cell survival from H(2)O(2)-induced toxicity, but also inhibited the H(2)O(2)-induced leakage of lactate dehydrogenase (LDH) enzyme release and DNA fragmentation significantly. It was also found that ECG showed scavenging activities of radicals and reactive oxygen species with IC(50) values of 20 microg/ml against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 52 microg/ml against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Topically applied ECG dose-dependently inhibited arachidonic acid (AA)- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, the present results suggest the therapeutic potential of ECG for acute skin inflammation that may involve oxidative tissue damage.

Antioxidative and acute antiinflammatory effects of Torreya grandis.

The present study was undertaken to investigate the antioxidative and antiinflammatory activities of the ethanolic extract of seeds of Torreya grandis (EST). Exposure of human dermal fibroblasts to the extract at 50 and 250 microg/ml showed significant protective effect against hydrogen peroxide (300 microM). EST not only protected cell survival from H(2)O(2)-induced toxicity, but also inhibited the H(2)O(2)-induced LDH release significantly. It was also found that EST at 100 and 1000 microg/ml showed scavenging activities of radicals and reactive oxygen species with 29.8% and 100.0% of inhibition against DPPH radical and 41.2% and 98.4% against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Topically applied EST dose-dependently inhibited arachidonic acid (AA)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice.

Tetrandrine, an alkaloid from S. tetrandra exhibits anti-hypertensive and sleep-enhancing effects in SHR via different mechanisms.

BACKGROUND: Sleep disorders have been found to be associated with hypertension in both cross-sectional and longitudinal epidemiological studies. Tetrandrine, a major component of Stephania tetrandra, is well known as an antihypertensive agent. The anti-hypertension mechanism mainly relies on its L-type calcium channel blocking property. In the previous study, tetrandrine revealed both anti-hypertension and hypnotic effects in spontaneously hypertensive rats (SHRs). PURPOSE: This study aims to elucidate whether the antihypertensive mechanism of tetrandrine in SHRs is relevant to its hypnotic effect. DESIGN/METHODS: Sleep-wake behavior of the SHRs was detected by electroencephalography (EEG) and electromyography (EMG) recordings. Blood pressure was measured by noninvasive blood pressure tail cuff test. Immunohistochemistry was performed to evaluate the noradrenergic neuronal activity. The level of norepinephrine (NE) was detected by HPLC-ECD. RESULTS: Amlodipine (100mg/kg, i.g.), the well-known L-type Ca2+ channel blockers (CCBs) exhibited remarkable antihypertensive activities in SHRs, but did not show effects on sleep of SHRs. Tetrandrine (30 and 60mg/kg/day, i.g.) significantly suppressed blood pressure of SHRs. Meanwhile, tetrandrine (60mg/kg/day, i.g.) remarkably increased non-rapid eye movement sleep (NREMS) time, bouts and mean duration. The hypnotic effect of tetrandrine was potentiated by prazosin (0.5mg/kg, i.p.) but attenuated by yohimbine (2mg/kg, i.p.). Administration of tetrandrine (60mg/kg/day, i.g.) not only significantly decreased c-Fos positive ratio of noradrenergic neurons in the locus coeruleus (LC), but also significantly decrease NE in the endogenous sleep-wake regulating pathways including LC, hypothalamus and ventrolateral preoptic nucleus (VLPO). CONCLUSION: In spite of a good potency in blocking L-type Ca2+ channel, the hypnotic effects of tetrandrine may be related to its suppressing effects on the noradrenergic system other than to block calcium channels. As a multi-targets drug, tetrandrine might be favorable to the hypertension patients who suffered poor sleep.