Nitric oxide mechanism in protective effect of imipramine and venlafaxine against acute immobilization stress-induced behavioral and biochemical alteration in mice

Frequent and persistent stressful events caused depressive illness. Stress is an aversive stimulus which disturbs physiological homeostasis and reflects a variety of biological systems. The present study was designed to investigate the nitric oxide mechanism in the protective effect of imipramine and venlafaxine against acute immobilization stress-induced behavioral and biochemical alterations in mice. Mice were immobilized for 6 h. Imipramine (10 and 20 mg/kg) and venlafaxine (5 and 10 mg/kg) were administered 30 min before subjecting the animals to acute stress. Behavioral tests (mirror chamber, actophotometer, tail flick test) and biochemical analysis (malondialdehyde level, nitrite, glutathione and catalase enzyme) were performed subsequently. Acute immobilization stress caused anxiety like behavior, analgesia, impaired locomotor activity and oxidative stress as compared to naive. Pretreatment with imipramine (10 and 20 mg/kg) and venlafaxine (5 and 10 mg/kg) significantly reversed immobilized stress-induced behavioral and biochemical alterations. l-arginine (100 mg/kg) pretreatment with imipramine (10 mg/kg) and venlafaxine (5 mg/kg) significantly attenuated the protective effect of imipramine and venlafaxine. However, l-NAME (10 mg/kg) and/or methylene blue (10 mg/kg) pretreatment with lower dose of imipramine and venlafaxine significantly potentiated their protective effects which were significant as compared to their effect per se respectively. Present study highlights the involvement of nitric oxide mechanism in the protective effect of imipramine and venlafaxine against acute immobilization-induced behavioral and biochemical alterations in mice.     

Sleep deprivation and cellular responses to oxidative stress

STUDY OBJECTIVES: It has been hypothesized that sleep deprivation represents an oxidative challenge for the brain and that sleep may have a protective role against oxidative damage. This study was designed to test this hypothesis by measuring in rats the effects of sleep loss on markers of oxidative stress (oxidant production and antioxidant enzyme activities) as well as on markers of cellular oxidative damage (lipid peroxidation and protein oxidation). DESIGN: The analyses were performed in the brain and in peripheral tissues (liver and skeletal muscle), after short-term sleep deprivation (8 hours), after long-term sleep deprivation (3-14 days), and during recovery sleep after 1 week of sleep loss. Short-term sleep deprivation was performed by gentle handling; long-term sleep deprivation was performed using the disk-over-water method. SETTING: Sleep research laboratory at University of Wisconsin-Madison. PARTICIPANTS AND INTERVENTIONS: Adult male Wistar Kyoto rats (n = 69) implanted for polygraphic (electroencephalogram, electromyogram) recording. MEASUREMENTS AND RESULTS: Aliquots of brain, liver, or skeletal muscle homogenate were used to assess oxidant production, superoxide dismutase activity, lipid peroxidation, and protein oxidation. No evidence of oxidative damage was observed at the lipid and/or at the protein level in long-term sleep-deprived animals relative to their yoked controls, nor in the cerebral cortex or in peripheral tissues. Also, no consistent change in antioxidant enzymatic activities was found after prolonged sleep deprivation, nor was any evidence of increased oxidant production in the brain or in peripheral tissues. CONCLUSION: The available data do not support the assumption that prolonged wakefulness may cause oxidative damage, nor that it can represent an oxidative stress for the brain or for peripheral tissue such as liver and skeletal muscle.     

Ketoconazole-induced testicular damage in rats reduced by Gentiana extract

Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. The protective effect of Gentiana (GEN) extract (Gentiana lutea) against KET-induced testicular damage was evaluated in male Wistar rats. GEN extract was administered orally (1 g/kg b wt/day) for 26 days. Three weeks after extract administration, KET was co-administered intraperitoneally at a dose of 100 mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. KET also induced severe testicular histopathological lesions such as degeneration of the seminiferous tubules and depletion of germ cells. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidants (catalase (CAT) and superoxide dismutase (SOD)) were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of GEN extract. This study suggests a protective role of GEN extract that could be attributed to its antioxidant properties.     

The evaluation of effects of lipoic acid on the lipid peroxidation,nitrite formation and antioxidant enzymes in the hippocampus of rats after pilocarpine-induced seizures

It has been suggested that pilocarpine-induced seizures is mediated by increases in oxidative stress. Current researches have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the neuroprotective effects of lipoic acid (LA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 6 h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA were also evaluated on the same parameters. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite level. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the superoxide dismutase and catalase activities in hippocampus of rats after seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that strong protective effect could be achieved using lipoic acid as an antioxidant.     

Effects of oleanolic acid on pulmonary morphofunctional and biochemical variables in experimental acute lung injury

We analysed the effects of oleanolic acid (OA) on lung mechanics and histology and its possible mechanisms of action in experimental acute lung injury (ALI). BALB/c mice were randomly divided into Control (saline, ip) and ALI (paraquat, 25 mg/kg, ip) groups. At 1 h, both groups were treated with saline (SAL, 50 μl ip), OA (10 mg/kg ip), or dexamethasone (DEXA, 1 mg/kg ip). At 24 h, lung static elastance, viscoelastic pressure, and alveolar collapse reduced more after OA compared to DEXA administration. Tumour necrosis factor-α, macrophage migration inhibitory factor, interleukin-6, interferon-γ, and transforming growth factor-β mRNA expressions in lung tissue diminished similarly after OA or DEXA. Conversely, only OA avoided reactive oxygen species generation and yielded a significant decrease in nitrite concentration. OA and DEXA restored the reduced glutathione/oxidized glutathione ratio and catalase activity while increasing glutathione peroxidase induced by paraquat. In conclusion, OA improved lung morphofunction by modulating the release of inflammatory mediators and oxidative stress.     

Sleep deprivation predisposes liver to oxidative stress and phospholipid damage: a quantitative molecular imaging study

Sleep disorders are associated with an increased rate of various metabolic disturbances, which may be related to oxidative stress and consequent lipid peroxidation. Since hepatic phosphatidylcholine plays an important role in metabolic regulation, the aim of the present study was to determine phosphatidylcholine expression in the liver following total sleep deprivation. To determine the effects of total sleep deprivation, we used adult rats implanted for polygraphic recording. Phosphatidylcholine expression was examined molecularly by the use of time-of-flight secondary ion mass spectrometry, along with biochemical solid-phase extraction. The parameters of oxidative stress were investigated by evaluating the hepatic malondialdehyde levels as well as heat shock protein 25 immunoblotting and immunohistochemistry. In normal rats, the time-of-flight secondary ion mass spectrometry spectra revealed specific peaks (m/z 184 and 224) that could be identified as molecular ions for phosphatidylcholine. However, following total sleep deprivation, the signals for phosphatidylcholine were significantly reduced to nearly one-third of the normal values. The results of solid-phase extraction also revealed that the phosphatidylcholine concentration was noticeably decreased, from 15.7 micromol g-1 to 9.4 micromol g-1, after total sleep deprivation. By contrast, the biomarkers for oxidative stress were drastically up-regulated in the total sleep deprivation-treated rats as compared with the normal ones (4.03 vs. 1.58 nmol mg-1 for malondialdehyde levels, and 17.1 vs. 6.7 as well as 1.8 vs. 0.7 for heat shock protein 25 immunoblotting and immunoreactivity, respectively). Given that phosphatidylcholine is the most prominent component of all plasma lipoproteins, decreased expression of hepatic phosphatidylcholine following total sleep deprivation may be attributed to the enhanced oxidative stress and the subsequent lipid peroxidation, which would play an important role in the formation or progression of total sleep deprivation-induced metabolic diseases.     

A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normal-weight healthy men

Sleep loss is currently proposed to disturb endocrine regulation of energy homeostasis leading to weight gain and obesity. Supporting this view, a reduction of sleep duration to 4 h for two consecutive nights has recently been shown to decrease circulating leptin levels and to increase ghrelin levels, as well as self-reported hunger. We hypothesized that similar endocrine alterations occur even after a single night of sleep restriction. In a balanced order, nine healthy normal-weight men spent three nights in our sleep laboratory separated by at least 2 weeks: one night with a total sleep time of 7 h, one night with a total sleep time of 4.5 h and one night with total sleep deprivation (SD). On a standard symptom-rating scale, subjects rated markedly stronger feelings of hunger after total SD than after 7 h sleep (3.9 ± 0.7 versus 1.7 ± 0.3; P  = 0.020) or 4.5 h sleep (2.2 ± 0.5; P  = 0.041). Plasma ghrelin levels were 22 ± 10% higher after total SD than after 7 h sleep (0.85 ± 0.06 versus 0.72 ± 0.04 ng mL⁻¹; P  = 0.048) with intermediate levels of the hormone after 4.5 h sleep (0.77 ± 0.04 ng mL⁻¹). Serum leptin levels did not differ between conditions. Feelings of hunger as well as plasma ghrelin levels are already elevated after one night of SD, whereas morning serum leptin concentrations remain unaffected. Thus, our results provide further evidence for a disturbing influence of sleep loss on endocrine regulation of energy homeostasis, which on the long run may result in weight gain and obesity.     

A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo

STUDY OBJECTIVES: To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers. DESIGN: Randomized, double-blind, placebo- and active-controlled, 3-way crossover. SETTING: Single research center. PARTICIPANTS AND INTERVENTIONS: Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days. MEASUREMENTS AND RESULTS: Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments. CONCLUSIONS: Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.     

Sleep Deprivation Alters Gene Expression and Antioxidant Enzyme Activity in Mice Splenocytes

Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep‐deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses.     

Catechin,quercetin and taxifolin improve redox and biochemical imbalances in rotenone-induced hepatocellular dysfunction: Relevance for therapy in pesticide-induced liver toxicity?

Hepatotoxicity occurs as a result of adverse effects of some xenobiotics on the liver, which is often the target tissue of toxicity for environmental chemicals. Rotenone, used as a natural pesticide, is an environmental poison reported to cause organ toxicity. This study investigated the protective effect of three flavonoids, catechin, quercetin and taxifolin (2,3-Dihydroquercetin) in rotenone-induced hepatotoxicity. Male Wistar rats were administered rotenone for 10 days followed by post treatment with catechin (5, 10 and 20?mg/kg), quercetin (5, 10 and 20?mg/kg) or taxifolin (0.25, 0.5 and 1?mg/kg), respectively, for 3 days. Bioindices of oxidative stress and hepatocellular injury were measured in serum and tissue homogenate of animals. Rotenone intoxication produced liver damage in rats as reflected in alterations to activities/levels of enzymic and non-enzymic oxidative stress markers and enzymes linked with inflammation, as well as the transaminases, gamma glutamyl transpeptidase, bilirubin, and lactate dehydrogenase. Catechin, quercetin and taxifolin post treatment significantly attenuated these (p?<?0.0001) rotenone-induced imbalances. Comparatively, quercetin displayed the best apparent ameliorative activity. It clearly showed superior activity to catechin. However, taxifolin appeared to show comparable activity to quercetin and better activity than catechin in some of the assays despite being administered at considerably lower doses. The results provide insight on the relative efficacy and structure-activity relationships of the selected flavonoids in ameliorating liver damage and also indicate that additional structural and metabolic factors may be involved in the structure-activity relationships of flavonoids.     

The effects of dopaminergic agonists on genital reflexes in paradoxical sleep-deprived male rats

Dopamine (DA) agonists provide evidence that different receptor subtypes in the central nervous system (CNS) have influence in sexual behavior. Sleep deprivation induces supersensibility of DA receptors and previous work has shown that the DA agonist apomorphine enhances spontaneous genital reflexes (penile erection-PE and ejaculation-EJ) in rats deprived of paradoxical sleep. The present study sought to extend the latter finding by assessing the effects of other DA agonists in paradoxical sleep-deprived (PSD) male rats. The DA drugs (bromocriptine and piribedil) were acutely administered to rats that had been deprived of sleep for 4 days and to normal controls. Sleep deprivation alone induced PE and this effect was potentiated by piribedil, with maximal effects occurring with the 8 mg/kg dose, whereas only one dose of bromocriptine (8 mg/kg) induced more PE in PSD rats than in non-deprived treated controls. EJs were increased in piribedil PSD groups but this response was absent after bromocriptine treatment in the dose range tested. Our data show the genital reflexes that occurred in PSD rats are potentialized by piribedil and not by bromocriptine. These DA agonists showed distinct effects in sexual response suggesting that these effects are probably due to PSD-induced DA receptor supersensitivity even though different mechanisms are involved.     

Sleep deprivation and daily torpor impair object recognition in Djungarian hamsters

Sleep has been shown to play a facilitating role in memory consolidation, whereas sleep deprivation leads to performance impairment both in humans and rodents. The effects of 4-h sleep deprivation on recognition memory were investigated in the Djungarian hamster (Phodopus sungorus). Because sleep during the first hours after daily torpor has many similarities to recovery from sleep deprivation, the effects of spontaneous torpor on object recognition were also assessed. A 4-h sleep deprivation, starting immediately after an object learning task, diminished the ability of the hamsters to: (1) discriminate between an already encountered object (target) and a novel object presented in a novel context, (2) retrieve a target within a complex spatial scene, and (3) detect a spatial rearrangement of familiar objects in a familiar context. Plasma stress hormone levels were similar in sleep-deprived and control hamsters. The occurrence of a daily torpor episode during retention was associated with impaired old-new object discrimination performance in the more effortful complex spatial scene task only, and in a two-object choice situation in a novel context no torpor-induced deficit was found. Our results show that post learning sleep deprivation and daily torpor induce a deficit in familiar object retrieval performance in a complex spatial scene, while sparing familiarity-based recognition and novelty processing. Sleep deprivation during the first 4 h of memory consolidation hampered also recency memory for discrete objects. Stress was not a factor contributing to the sleep deprivation-induced impairment.     

Sodium valproate improves sensorimotor gating deficit induced by sleep deprivation at low doses

Background/aim Sleep deprivation disrupts prepulse inhibition of acoustic startle reflex and can be used to mimic psychosis in experimental animals. On the other hand, it is also a model for other disorders of sensory processing, including migraine. This study aims to assess the effects of sodium valproate, a drug that is used in a variety of neuropsychiatric disorders, on normal and disrupted sensorimotor gating in rats.Materials and methods Sixty-two Wistar albino rats were randomly distributed into 8 groups. Subchronic and intraperitoneal sodium valproate were administrated to the sleep-deprived and nonsleep-deprived rats by either 50–100 or 200 mg/kg/day. Prepulse inhibition test and locomotor activity test were performed. Sleep deprivation induced by the modified multiple platform method.Results Sleep deprivation impaired prepulse inhibition, decreased startle amplitude, and increased locomotor activity. Sodium valproate did not significantly alter prepulse inhibition and locomotor activity in nonsleep-deprived and sleep-deprived groups. On the other hand, all doses decreased locomotor activity in drug-treated groups, and low dose improved sensorimotor gating and startle amplitude after sleep deprivation.Conclusion Low-dose sodium valproate improves sleep deprivation-disrupted sensorimotor gating, and this finding may rationalize the use of sodium valproate in psychotic states and other sensory processing disorders. Dose-dependent effects of sodium valproate on sensorimotor gating should be investigated in detail.     

Selenium provides protection to the liver but not the reproductive organs in an atrazine-model of experimental toxicity

The present study evaluated the possible protective effects of selenium against atrazine-induced toxicity in the liver and reproductive system of rats. Atrazine administered to rats orally at a dose of 120 mg/kg caused an inhibition in the activity of glutathione-S-transferase and an increase in malondialdehyde formation in the liver, testis and epididymis. Superoxide dismutase decreased in the liver and testis but was increased in the epididymis. Furthermore, hepatic glutathione and lactate dehydrogenase activity increased while epididymal catalase, ascorbate content, hepatic aspartate aminotransferase and glutathione peroxidase activities in all the tissues decreased in the atrazine-treated animals. Hepatic, testicular and epididymal alanine aminotransferase activities were not affected by atrazine (p>0.05). Decreased epididymal and testicular sperm number, sperm motility, daily sperm production and increased number of dead and abnormal sperm were observed in atrazine-treated rats.Treatment of rats orally with selenium at a dose of 0.25 mg/kg did not prevent atrazine-induced changes in sperm characteristics and had no protective effects against atrazine-induced biochemical alterations in the testis and epididymis except testicular lactate dehydrogenase. Catalase activity and ascorbate contents were unchanged in these groups of animals. However, selenium effectively protected against atrazine-induced changes in biochemical indices in the liver. In rats treated with selenium alone, glutathione peroxidase in all the tissues, hepatic glutathione and superoxide dismutase, testicular lactate dehydrogenase activity and ascorbate content increased, while hepatic catalase activities decreased (p<0.05).Our data suggest that selenium effectively attenuated the toxic effects of atrazine-induced liver changes but not in the reproductive organs and sperms of rats. Selenium might therefore be useful in ameliorating oxidative stress in the liver.     

Effects of sleep deprivation on impulsive behaviors in men and women

The purpose of this study was to examine the effects of sleep deprivation on impulsive behavior. Patients with impulse control disorders often report sleep problems, and sleep deprivation even in healthy individuals impairs cognition, decision-making, and perhaps impulse control. To characterize the effects of sleep loss on specific forms of impulsive behavior, we tested the effects of overnight, monitored sleep deprivation on measures of impulsivity and cognition in healthy volunteers. Ten men and ten women completed two 24 h sessions in random order, in which they were either allowed to sleep normally or remained awake all night. At 8:30 am and 6:15 pm on the day after sleep or no sleep, participants were tested on the Balloon Analogue Risk Task (BART), the Experiential Discounting Task, the Adjusting Amount Delay and Probability Discounting Task, and the Stop Task. Participants also completed mood questionnaires and the Automated Neuropsychological Assessment Matrix (ANAM) throughout the course of the day. Sleep deprivation did not affect most of the measures of impulsive behavior. However, on the BART, sleep deprivation decreased risk taking in women, but not men. Sleep deprivation produced expected increases in subjective fatigue, and impaired performance on measures of attention and cognitive efficiency on the ANAM. The results indicate that sleep deprivation does not specifically increase impulsive behaviors but may differentially affect risk taking in men and women.     

Mapping Slow Waves by EEG Topography and Source Localization: Effects of Sleep Deprivation

Slow waves are a salient feature of the electroencephalogram (EEG) during non-rapid eye movement (non-REM) sleep. The aim of this study was to assess the topography of EEG power and the activation of brain structures during slow wave sleep under normal conditions and after sleep deprivation. Sleep EEG recordings during baseline and recovery sleep after 40 h of sustained wakefulness were analyzed (eight healthy young men, 27 channel EEG). Power maps were computed for the first non-REM sleep episode (where sleep pressure is highest) in baseline and recovery sleep, at frequencies between 0.5 and 2 Hz. Power maps had a frontal predominance at all frequencies between 0.5 and 2 Hz. An additional occipital focus of activity was observed below 1 Hz. Power maps?≤?1 Hz were not affected by sleep deprivation, whereas an increase in power was observed in the maps?≥?1.25 Hz. Based on the response to sleep deprivation, low-delta (0.5–1 Hz) and mid-delta activity (1.25–2 Hz) were dissociated. Electrical sources within the cortex of low- and mid-delta activity were estimated using eLORETA. Source localization revealed a predominantly frontal distribution of activity for low-delta and mid-delta activity. Sleep deprivation resulted in an increase in source strength only for mid-delta activity, mainly in parietal and frontal regions. Low-delta activity dominated in occipital and temporal regions and mid-delta activity in limbic and frontal regions independent of the level of sleep pressure. Both, power maps and electrical sources exhibited trait-like aspects.     

睡眠剥夺后大鼠海马生化及病理变化

目的 :观察睡眠剥夺后大鼠海马超微结构的病理变化及一氧化氮 (NO)含量、超氧化物歧化酶 (SOD)活力变化。方法 :以小平台水环境法建立大鼠睡眠剥夺模型 ,并设立大平台对照组 ,分离海马 ,电镜观察海马神经细胞超微结构变化、测定海马组织匀浆NO含量和SOD活力。结果 :睡眠剥夺组大鼠海马NO含量及SOD活力均高于大平台组和正常对照组 (P <0 0 5 )。病理形态学改变 ,光镜电镜下海马神经元减少 ,核仁碎裂、胞质内细胞器减少。结论 :睡眠剥夺可引起海马NO含量和SOD活力增高 ,并且存在病理形态学改变     

Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E

Organophosphorus insecticide poisoning is widely investigated, and a growing number of evidence indicates its effects to cause ocular lesions, but the mechanisms of its ocular effects are not well elucidated. Here, effects of organophosphorus insecticide chlorpyrifos on mouse retina in vivo and protection of combination of vitamins C and E were reported. Cell apoptosis, lipid peroxidation and DNA damage were increased, and activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were decreased in retina of chlorpyrifos-administrated mice (63 mg/kg, single treatment, via oral gavage). Pretreatment of combination of antioxidants vitamin C (250 mg/kg) and vitamin E (150 mg/kg) (once daily for 6 days, hypodermic injecting) significantly attenuated these effects of chlorpyrifos, demonstrating oxidative stress was involved in chlorpyrifos-induced cell apoptosis in mouse retina. Moreover, chlorpyrifos treatment inhibited acetylcholinesterase activity and promoted [Ca²⁺]_i level in mouse retinal cells, which were also attenuated by combination of vitamins C and E. These results may have implications for treatment of organophosphorus insecticide poisoning in retina with combination of vitamins C and E.     

Effects of sleep deprivation on memory in mice: role of state-dependent learning

Study Objectives:

A considerable amount of experimental evidence suggests that sleep plays a critical role in learning/memory processes. In addition to paradoxical sleep, slow wave sleep is also reported to be involved in the consolidation process of memories. Additionally, sleep deprivation can induce other behavioral modifications, such as emotionality and alternations in locomotor activity in rodents. These sleep deprivation-induced alterations in the behavioral state of animals could produce state-dependent learning and contribute, at least in part, to the amnestic effects of sleep deprivation. The aim of the present study was to examine the participation of state-dependent learning during memory impairment induced by either paradoxical sleep deprivation (PSD) or total sleep deprivation (TSD) in mice submitted to the plus-maze discriminative avoidance or to the passive avoidance task.

Design:

Paradoxical sleep deprivation (by the multiple platform method) and total sleep deprivation (by the gentle handling method) were applied to animals before training and/or testing.

Conclusions:

Whereas pre-training or pre-test PSD impaired retrieval in both memory models, pre-training plus pre-test PSD counteracted this impairment. For TSD, pre-training, pre-test, and pre-training plus pre-test TSD impaired retrieval in both models. Our data demonstrate that PSD- (but not TSD-) memory deficits are critically related to state-dependent learning.

Citation:

Patti CL; Zanin KA; Sanday L; Kameda SR; Fernandes-Santos L; Fernandes HA; Andersen ML; Tufik S; Frussa-Filho R. Effects of sleep deprivation on memory in mice: role of state-dependent learning. SLEEP 2010;33(12):1669-1679.     

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.