Temporal perception in closed-skill sports: An experimental study on expert swimmers and runners.

The cognitive benefits of closed-skill sports practice have so far been scantily investigated. Here, we thus focused on the potential impact of swimming and running - two sports that highly rely on a precise control of timing - on time processing. To investigate the impact of these closed-skill sports on time perception and estimation, three groups of participants (for a total of eighty-four young adults) took part in the present study: expert swimmers, expert runners, and non-athletes. The ability to process temporal information in the milliseconds and seconds range was assessed through a time reproduction and a finger-tapping tasks, while a motor imagery paradigm was adopted to assess temporal estimation of sport performance in a wider interval range. We also employed the Vividness of Movement Imagery Questionnaire to assess the individual's ability of motor imagery. Results showed that closed-skill sports, specifically time-related disciplines, enhance motor imagery and time perception abilities. Swimmers were more accurate and consistent in perceiving time when compared to runners, probably thanks to the sensory muffled environment that leads these athletes to be more focused on the perception of their internal rhythm.

Environmental enrichment affects behavioral and pharmacological response to antidepressants in CF1 mice.

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.

Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System.

Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5-5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT2A/2C and 5-HT4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD.

Long-lasting and sex-dependent effects of late lactational maternal deprivation on socioemotional behaviors in adult mice.

The lactation period is an important period for individual development and a sensitive period for the behavioral phenotypes and plasticity of individual offspring. Early life experiences (e.g., maternal deprivation (MD) and neglect) have significant long-lasting and dual effects on individual stress reactivities during adulthood. Theoretically, stress inoculation can improve the adaptive capacity of the body, but overstress can lead to dysfunction when adaptive mechanisms fail.To date, the potential effects of late lactational MD on the socioemotional behaviors of mouse offspring during adulthood are still not fully understood. In the present study, mice were subjected to early deprivation by individually separating pups from their dam for 0 min, 15 min, and 3 h per day from PND 13-25. The social dominance test (SDT), social interaction test (SI), open field test (OFT), and forced swim test (FST) were carried out during adulthood. The results showed that the social dominance of male mice in the 15 min/d MD group significantly increased, especially in low-rank mice. In the 3 h/d MD group, the social dominance of female mice was decreased, especially in the lower-rank mice. The anxiolytic and antidepressant-like effects of the 15 min/d MD group were significantly increased in male mice. Our study provides direct evidence that MD during late lactation period results in long-lasting effects on social dominance as well as on anxiety and depression phenotypes in a sex-dependent manner.

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System.

The present study investigated the antidepressant-like potential of a functionalized 3-selanyl benzo[b]furan (SeBZF) in male Swiss mice. To evaluate possible antidepressant-like actions, the compounds SeBZF1-5 (50 mg/kg, intragastric, i.g., route) were acutely screened in the tail suspension tests (TSTs). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) was then selected. Dose-response and time-response curves revealed that SeBFZ3 exerts antidepressant-like effects in the TST (5-50 mg/kg) and forced swimming test (FST; 50 mg/kg). Additional tests demonstrated that pretreatment with receptor antagonists WAY100635 (5-HT1A; 0.1 mg/kg, subcutaneous route), ketanserin (5-HT2A/C; 1 mg/kg, intraperitoneal, i.p.), or ondansetron (5-HT3; 1 mg/kg, i.p.) blocked the SeBZF3 antidepressant-like effects (50 mg/kg) in the TST. In addition, the coadministration of subeffective doses of SeBZF3 (1 mg/kg, i.g.) and fluoxetine (a selective serotonin reuptake inhibitor; 5 mg/kg, i.p.) produced synergistic action. A high dose of SeBZF3 (300 mg/kg) did not produce oral acute toxicity. The present results provide evidence for the antidepressant-like action of SeBZF3 and its relative safety, as well as predict the possible interactions with the serotonergic system, aiding in the development of novel options to alleviate psychiatric disabilities.

[A new method for assessing depressive-like behaviors in female mice].

Depression is a common mental disorder and mainly characterized by persistent sadness and a lack of interest or pleasure in previously rewarding or enjoyable activities. Despair is also a common symptom of depression, and the forced swim and tail suspension tests are widely used to measure this behavior in rodents, but the results from these tests can include the effects on stress resistance in addition to depressive-like states. Reduced motivation is an important marker of psychiatric disorders, including depression, and thus we have previously developed the female encounter test, a novel and simple procedure for assessing reward-seeking behavior in adult male mice. Importantly, female mice should be considered in the development of animal models of depression and assessment of mouse behaviors since the lifetime prevalence of a major depressive disorder in women is almost twice that in men, and around one in seven women can develop postpartum depression. In this review, we summarized our recent research on the male encounter test for assessing motivation in adult female mice and introduced new topics on animal models and therapeutic drugs for postpartum depression.

The Effect of Halliwick Method on Aquatic Skills of Children with Autism Spectrum Disorder.

BACKGROUND: Swimming and the skills associated with participation in the aquatic environment tend to be an integral part of the movement literacy complex. Non-participation then affects the safety of movement in the aquatic environment and may also be the reason for the limitation of movement, psychological, and social development compared to peers. METHODS: This study is a single-subject research study. The aim of this study is to evaluate the effect of a seven-week intervention program of the Halliwick method in the development of aquatic skills, gross motor skills, and mental skills relevant for aquatic competence for children with autism spectrum disorder. Seven children with autism spectrum disorder participated in swimming classes for a two-week baseline period and a seven-week intervention program of the Halliwick method, one time per week. To measure the effect in the field of aquatic skills, we used the Alyn Water Orientation Test 1. To determine the level of gross motor skills, we used the Gross Motor Function Measure test. RESULTS: There was an improvement in aquatic skills and gross motor skills in seven participants; two of them did not improve in mental adjustment oriented to the breathing control sections in the water.

Central injection of abscisic acid attenuates mood disorders induced by subchronic stress in male mice.

Stressful life increases the risk of mental and psychological disorders and cognitive deficits. Abscisic acid (ABA) is a plant hormone that has been recently discovered in mammalians. ABA is produced in response to stressful stimuli and it can reduce anxiety-like behaviors and depression and improve cognitive function. This study was designed to evaluate the effects of microinjection of ABA on depression, anxiety, passive avoidance learning and memory deficits induced by subchronic stress. ABA (10 and 15  µ $\umu $ g/mouse, i.c.v.) was administered one week after recovery period for 4 consecutive days. A three-session forced swimming test (FST) protocol for induction of subchronic stress was administered to the mice. Exploratory, anxiety-like behavior, depression and cognitive function were assessed 24 h after the last swim stress session. The results indicated that ABA (15  µ $\umu $ g/mouse) could ameliorate anxiety and depression induced by FST. In addition, ABA had no effect on the subchronic stress-induced cognitive impairments. Taken together, the results suggest that ABA could improve anxiety and depression induced by subchronic stress.

Swimming exercise strain-dependently affects maternal care and depression-related behaviors through gestational corticosterone and brain serotonin in postpartum dams.

Pregnancy is a very complex and highly stressful time in which women become more physically and emotionally vulnerable. Therefore, mothers are more likely to face decreased self-esteem and increased postpartum depression. Despite the high prevalence of postpartum depression, more than 50 % of mothers are undiagnosed or untreated, showing an urgent need to explore an effective preventive strategy. A healthy lifestyle and regular physical activity have been suggested to be associated with an increased quality of life in pregnant and postpartum women. The purpose of this study was to determine whether swimming exercise before and during pregnancy can affect maternal care and postpartum depression-related behaviors in dams. To this end, female NMRI and C57BL/6 J mice were subjected to swimming exercise before conception and throughout pregnancy. On postpartum days 1-2, maternal behavior including nest building, active nursing, and licking/grooming were monitored. A battery of behavioral tests was also used to measure depression-related symptoms including anhedonia- and anxiety-like behavior, social behavior, and behavioral despair. To identify the underlying mechanisms, corticosterone and inflammatory cytokines during late pregnancy, and corticosterone and brain serotonin during the postpartum period were measured in dams. The findings indicated that swimming exercise increased gestational corticosterone, decreased maternal care and brain serotonin, and increased all depression-related behaviors in postpartum C57BL/6 J dams, while only increased licking/grooming and social behavior, and reduced anhedonia-like behavior in postpartum NMRI dams. Taken together, this study suggests that swimming exercise before and during pregnancy could alter maternal care and postpartum depression-like behavior in a strain-dependent manner.

Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies.

Psilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has been used extensively to evaluate compounds for antidepressant efficacy, has recently been adapted for Drosophila. The fly FST has potential to be a cost-effective, high-throughput assay for evaluating potential antidepressants. For this study we pharmacologically validated the fly FST using methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. While methamphetamine and DL-α-methyltyrosine altered overall locomotor activity in the Drosophila Activity Monitor System (DAMS), they had no significant impact on measures of immobility in the FST. Conversely, chronic citalopram decreased measures of immobility in the FST in both sexes without increasing DAMS activity. We used the validated FST to evaluate the antidepressant-like effects of high (3.5 mM) and low (0.03 mM) doses of psilocybin. Both doses of psilocybin significantly reduced measures of immobility in male flies, but not females. 0.03 mM had an effect size comparable to chronic citalopram, and 3.5 mM had an effect size approximately twice that of chronic citalopram.

Thermoregulatory significance of immobility in the forced swim test.

The forced swim test (FST) is a widely used animal model of depression and antidepressant drug screen. Rats are forced to swim on two test days in a restricted space from which there is no escape. On the first test day the rats attempt to escape and then become largely immobile; on the second test day the onset of immobility is more rapid. Immobility is said to reflect a state of lowered mood or "behavioral despair", but the validity of the FST as a model of depression has been questioned. We show here that whatever psychological states the FST may induce, immobility is water temperature dependent and thermoregulatory. In Experiment 1, separate groups of rats were first tested in water of 15, 20, 22, 25, 30, 35, 37, or 40 °C. When retested at the same temperature, reduced activity was evident only in those groups tested above 20 °C and below 37 °C. On a third test, rats previously tested in 35 °C water failed to show reduced activity in 15 °C water, whereas rats previously tested at 15 °C water did exhibit reduced activity when tested in 35 °C water. Thus, activity was dependent on current water temperature rather than prior experience. In Experiment 2, activity and body temperature were monitored during 30 min swim tests in 27 °C water. The more the animals moved, the greater the loss of body temperature. The results are consistent with a hypothesis that immobility in the FST is an adaptive thermoregulatory response that increases survival by minimizing convective heat loss. This interpretation is also aligned with best practices for survival of humans in water that is below thermoneutral.

Sex and estrous-phase dependent alterations in depression-like behavior following mild traumatic brain injury in adolescent rats.

Following mild traumatic brain injury (TBI), high school and collegiate-aged females tend to report more emotional symptoms than males. Adolescent male and female rats (35 days old) were subjected to mild TBI and evaluated for anxiety- and depression-like behaviors using the elevated plus maze and forced swim test (FST), respectively, and cellular alterations. Injured brains did not exhibit an overt lesion, atrophy of tissue or astrocytic reactivity underneath the impact site at 6-week post-injury, suggestive of the mild nature of trauma. Neither male nor female brain-injured rats exhibited anxiety-like behavior at 2 or 6 weeks, regardless of estrous phase at the time of behavior testing. Brain-injured male rats did not exhibit any alterations in immobility, swimming and climbing times in the FST compared to sham-injured rats at either 2- or 6-week post-injury. Brain-injured female rats did, however, exhibit an increase in immobility (in the absence of changes in swimming and climbing times) in the FST at 6 weeks post-injury only during the estrus phase of the estrous cycle, suggestive of a depression-like phenotype. Combined administration of the estrogen receptor antagonist, tamoxifen, and the progesterone receptor antagonist, mifepristone, during proestrus was able to prevent the depression-like phenotype observed during estrus. Taken together, these data suggest that female rats may be more vulnerable to exhibiting behavioral deficits following mild TBI and that estrous phase may play a role in depression-like behavior.

Histological assessment of liver and stomach damage caused by pyridazinone derivative antidepressant agents.

Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine. The most promising compound was compound 2, which reduced the duration of immobility during FST. The toxic effects of the four compounds on the histomorphology of the liver and stomach tissue also was evaluated.

Ansiedad precompetitiva y motivación en nadadores costarricenses de élite / Precompetitive Anxiety and Motivation in Costa Rica Elite Swimmers

Resumen El objetivo de esta investigación es describir el manejo de la ansiedad precompetitiva en nadadores y nadadoras costarricenses de élite, entre los 14 y 22 años, identificando los elementos motivantes (externos e internos) y el cómo influye la relación de dichos atletas con su entrenador y con su grupo de pares en los procesos de motivación y ansiedad precompetitiva. Para ello se realizaron entrevistas semiestructuradas a finales del año 2018. Los resultados sugieren que entre los principales elementos asociados con mayores sensaciones de ansiedad se encuentran la falta de objetivos alcanzados antes de la competencia, el tener un bajo rendimiento durante los entrenamientos y estar al tanto de la importancia de la competición respectiva. Sus motivaciones se han clasificado en intrínsecas (competición olímpica, mejora de tiempos, ubicación en ránkings) y extrínsecas (familia, entrenador, equipo). Al existir una mala relación con el entrenador y su grupo de pares se pierde el interés de ir a entrenar y de competir. En conclusión, al presentar ansiedad precompetitiva, el rendimiento puede disminuir provocando un incumplimiento de objetivos, lo que lleva a que los atletas se empiecen a desmotivar, manteniendo la ansiedad para sus siguientes competiciones.

Abstract This study aims to describe the management of precompetitive anxiety in elite Costa Rican swimmers aged 14 to 22 years old, identifying the motivating elements (external and internal) and how the relationship with their coach and their peer group influences the processes of motivation and precompetitive anxiety. Semi-structured interviews were conducted by the end of 2018. The results suggest that among the main elements associated with greater feelings of anxiety are the lack of objectives achieved before the competition, having a poor performance during training, and being aware of the importance of the respective competition. The elite swimmers' motivations have been classified as intrinsic (Olympic competition, time improvement, placement in rankings) and extrinsic (family, coach, team) ones. Finally, results suggest that a bad relationship with the coach and peer groups could result in a loss of interest in training and competing. In conclusion, when presenting precompetitive anxiety, performance can decrease, causing non-fulfillment of objectives, which leads athletes to demotivate, maintaining anxiety for their next competitions.

Resumo O objetivo desta pesquisa é descrever o manejo da ansiedade pré-competitiva em nadadores de elite costarriquenhos entre 14 e 22 anos de idade, identificando os elementos motivadores (externos e internos) e como a relação desses atletas com seu treinador e com seu grupo influencia nos processos de motivação e ansiedade pré-competitiva. Para isso, foram realizadas entrevistas semiestruturadas no final de 2018. Os resultados sugerem que entre os principais elementos associados a maiores sentimentos de ansiedade estão a falta de objetivos alcançados antes da competição, o mau desempenho durante os treinos e a consciência da importância da respetiva competição. Suas motivações foram classificadas em intrínsecas (competição olímpica, melhora de tempo, colocação em rankings) e extrínsecas (família, técnico, equipe). Quando há um relacionamento ruim com o treinador e com seu grupo, existe uma perda de interesse em ir treinar e competir. Concluindo, ao apresentar ansiedade pré-competitiva, o desempenho pode diminuir causando o não cumprimento dos objetivos, o que leva os atletas a começarem a se desmotivar, mantendo a ansiedade para as próximas competições.

Anxiolytic, antidepressant and inhibitory effect on MAO isoenzymes by Bougainvillea glabra flower extract in rats.

Main aim of current study was to determine the anxiolytic and antidepressant potential of Bougainvillea glabra Extract (BVE). The effects were investigated by using Open-Field-Test (OFT), Light-and-Dark Model (LD), Hole-Board (HB) and Forced-Swimming-Test (FST). Different doses for BVE were given to Wistar-Rats and compared with Control and Diazepam. Data has been collected by simple observations of animal behaviors in mentioned models. Collected data was analyzed by SPSS-22 version. In OFT (number of squares travelled), significant differences noted between Control and BV100mg/kg (p=0.001), Diazepam and BV100mg/kg (p=0.0001), Diazepam and BV200mg/kg (p=0.015), Diazepam and BV300 mg/kg (p=0.002). In LD-Test, significant differences were noted between Control and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001), Diazepam and BV100mg/kg, 200mg/kg (p=0.0001), Diazepam and BV300mg/kg (p=0.028). In HB-Test by head dips, significant differences noted between control group and BV100mg/kg and 200mg/kg (p=0.0001), Control group and BV300mg/kg (p=0.005). For number of head dips, significant differences noted between Diazepam and BV100mg/kg, 200mg/kg and 300mg/kg (p=0.0001). In FST, significant differences were observed between Control group and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001), Fluoxetine and BV100mg/kg, BV200mg/kg and BV300mg/kg (p=0.0001). It is observed that MAO-A and MAO-B are inhibited by BVE. Study demonstrates that BV flowers have anxiolytic and antidepressant activities.

Increased efficacy of combining prebiotic and postbiotic in mouse models relevant to autism and depression.

The Microbiota-Gut-Brain axis (MGBA) is a bidirectional communication pathway between gut bacteria and the central nervous system (CNS) (including the intestine) that exerts a profound influence on neural development, neuroinflammation, activation of stress response and neurotransmission, in addition to modulating complex behaviours, such as sociability and anxiety. Several MGBA modulating approaches are possible, such as probiotic administration. A reasonable pharmacological approach would also be the contemporarily administration of both prebiotics and postbiotics. To test this hypothesis, we probed the effects of α-lactalbumin (ALAC; a prebiotic in the dose range of 125-500 mg/kg) and sodium butyrate (NaB; a postbiotic in the dose range of 30-300 mg/kg) alone and in combination. We used two animal behavioural models of idiopathic autism, (BTBR mice) and anxiety/depression (chronic unexpected mild stress - CUMS mice) respectively, using several standard behavioural paradigms such as Three-chamber social interaction test, Marble burying assay, depression-, anxiety- and memory-tests. In BTBR autistic mice, we found that both ALAC and NaB improve animal sociability, and memory in the passive avoidance (PA); drug combination was more effective in almost all tests also reducing immobility time in the forced swimming test (FST), which was not affected by single drug administration. Similarly, in the CUMS mice, single drug administration was effective in improving: 1) depressive-like behaviour in the FST and sucrose preference test; 2) memory and learning in the PA, novel object recognition and Morris water maze tests. Drug combination was again more effective than single drug administration in most cases; however, in the CUMS model, neither single drug or combination was effective in the elevated plus maze test for anxiety. Our results suggest that in both models, ALAC and NaB combination is more effective in improving some pathological aspects of animal behaviour than single administration and that the prebiotic/postbiotic approach should be considered a reasonable approach for the manipulation of the MGBA to improve efficacy.

Quercetin reverses chronic unpredictable mild stress-induced depression-like behavior in vivo by involving nuclear factor-E2-related factor 2.

Quercetin is a flavonoid compound rich in many natural plants with a wide range of pharmacological effects and nutritional value. Although previous studies have initially shown the antidepressant effect of quercetin in some models. However, the exact mechanism of the antidepressant effect of quercetin on the depression model induced by chronic unpredictable mild stress (CUMS) is still unclear or has not been clearly elucidated. The present study aimed to investigate the antidepressant effect of quercetin in vivo on a CUMS-induced depression model that is closest to human depression, and to explore its mechanism of action around nuclear factor-E2-related factor 2 (Nrf2) related signaling pathways, for the first time. Our results demonstrated that CUMS for 21 consecutive days caused significant decreases in the sucrose preference, and the horizontal score and vertical score in the open field test of mice respectively by 22.6%, 34.4%, and 66.6% (all P < 0.01), and a significant increase in the immobility time during the forced swimming test by 110.5% (P < 0.01), but fortunately, after chronic oral administration of high dose quercetin at 40 mg/kg, the abnormalities of the above indicators were significantly reversed by 26.2%, 40.1%, 152.7%, 43.5% (all P < 0.01). Further western blot analysis showed that CUMS caused the phosphorylation or expression levels of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), Nrf2 and heme oxygenase-1 (HO-1) proteins in the hippocampus of mice to significantly down-regulate by 60.0%, 72.1%, 90.0% and 50.1% (all P < 0.01), while after chronic oral administration of high dose quercetin at 40 mg/kg, the abnormalities of these proteins were significantly up-regulated by 85.8%, 182.0%, 325.1% and 60.3% (all P < 0.01). In addition, CUMS also caused significant reduction in the levels of antioxidants including superoxide dismutase (SOD) and glutathione-s transferase (GST) in the mice hippocampus by 51.3%, 40.3% (both P < 0.01), while after chronic oral administration of high dose quercetin at 40 mg/kg, the abnormalities of the above indicators were significantly reversed by 69.2% and 49.5% (both P < 0.01), as well as significant elevation in the levels of lipid peroxide malondialdehyde (MDA), inflammation medium nitric oxide (NO) and inducible nitric oxide synthase (iNOS) by 156.4%, 255.4% and 72.7% (all P < 0.01), while after chronic oral administration of high dose quercetin at 40 mg/kg, the abnormalities of the above indicators were significantly reversed by 45.9%, 26.8% and 55.2% (all P < 0.01). The medium dose of quercetin (20 mg/kg) only reversed some of the above indicators, while the low dose of quercetin (10 mg/kg) had no reversal effect on the above indicators. Collectively, the present study confirmed for the first time that quercetin weakened CUMS-induced depression in vivo, and its mechanism was at least partially attributable to the upregulation of hippocampal Nrf2 and the inhibition of iNOS, thereby correcting the central inflammatory response, and the imbalance between oxidation and antioxidant.

Neuronal correlates underlying the role of the zinc sensing receptor (GPR39) in passive-coping behaviour.

The Zn2+ receptor GPR39 is proposed to be involved in the pathophysiology of depression. GPR39 knockout (KO) animals show depressive- and anxiety-like behaviour, and resistance to conventional monoamine-based antidepressants. However, it is unclear as to which brain regions are involved in the pro-depressive phenotype of GPR39KO mice and the resistance to monoamine-targeting antidepressant treatment. Our current study confirmed previous results, showing that mice lacking GPR39 display enhanced passive coping-like behaviour compared with their wild-type controls. Furthermore, this study shows for the first time that GPR39KO displayed aberrant challenge-induced neuronal activity in key brain regions associated with passive coping behaviour. Imipramine induced only a marginal reduction in the enhanced passive coping behaviour in GPR39KO mice, which was associated with attenuation of the hyperactive prefrontal cortex. Similarly, the aberrant activity within the amygdalar subregions was normalized following imipramine treatment in the GPR39KO mice, indicating that imipramine mediates these effects independently of GPR39 in the prefrontal cortex and amygdala. However, imipramine failed to modulate the aberrant brain activity in other brain regions, such as the anterior CA3 and the dentate gyrus, in GPR39KO mice. Normalization of aberrant activity in these areas has been shown previously to accompany successful behavioural effects of antidepressants. Taken together, our data suggest that monoamine-based antidepressants such as imipramine exert their action via GPR39-dependent and -independent pathways. Failure to modulate passive-coping related aberrant activity in important brain areas of the depression circuitry is proposed to mediate/contribute to the greatly reduced antidepressant action of monoamine-based antidepressants in GPR39KO mice.

Swimming Improves Memory and Antioxidant Defense in an Animal Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disease associated with progressive skeletal muscle degeneration. In humans, DMD has an early onset, causes developmental delays, and is a devastating disease that drastically diminishes the quality of life of young individuals affected. The objective of this study was to evaluate the effects of a swimming protocol on memory and oxidative stress in an animal model of DMD. Male mdx and wild-type mice aged ≥ 28 days were used in this study. The animals were trained for a stepped swimming protocol for four consecutive weeks. The swimming protocol significantly reduced the levels of lipid peroxidation and protein carbonylation in the gastrocnemius, hippocampus, and striatum in the exercised animals. It also prevented lipid peroxidation in the diaphragm. Moreover, it increased the free thiol levels in the gastrocnemius, the diaphragm, and all central nervous system structures. The results showed that the protocol that applied swimming as a low-intensity aerobic exercise for 4 weeks prevented aversive memory and habituation in mdx mice.