Forced Swim Test Research Articles

Effect of naringin on sodium fluoride‑induced neurobehavioral deficits in Wistar rats.

There is a lack of treatment for the detrimental effects of fluorosis. Sodium fluoride at a concentration of 10 ppm induces stress, depression and memory impairment in adult Wistar rats. Naringin, a flavanone glycoside isolated from citrus fruits such as lemons and oranges, possesses anti-inflammatory, antioxidant and neuroprotective properties; therefore, it was used for treatment of fluoride induced toxicity in the present study. Adult Wistar rats were divided into eight groups (n=8). The normal control (NOR) group was provided with normal tap water. The sodium fluoride (FLU)10 group received water containing 10 ppm sodium fluoride for 60 days. The treatment groups (FLU10NAR100 and FLU10NAR50) received drinking water with 10 ppm sodium fluoride ad libitum along with Naringin 100 and 50 mg/kg body weight (bw) per oral gavage, respectively. The NAR100 and NAR50 groups received Naringin 100 and 50 mg/kg bw. The PRONAR100 and PRONAR50 groups received Naringin 100 and 50 mg/kg bw for the first 15 days and then subsequently received FLU10 ppm for 60 days (total of 75 days). All animals were subjected to behavioural tests consisting of the open field test (OFT), forced swim test (FST) and novel object recognition test (NORT). After euthanasia, the hippocampus and prefrontal cortex were stained with Cresyl violet. To measure the oxidative stress caused by fluoride and its effect on antioxidant levels, estimation of reduced glutathione (GSH) by Ellman's method, lipid peroxidation (LPO) measured in terms of the MDA:thiobarbituric acid reaction and catalase was performed. To evaluate the effect of fluoride on activity of acetylcholine, estimation of acetylcholinesterase (AChE) by Ellman's method was performed. In NORT and FST, significant changes (P<0.05) were present in the FLU10NAR100 and FLU10NAR50 groups compared with the FLU10 group, showing recovery from memory deficit and depression. The OFT results were insignificant. The LPO was reduced in all the other groups except the FLU10 group, with statistically significant changes. Catalase activity was significantly lower in FLU10 as compared with the NAR100, NAR50, PRONAR100 and PRONAR50 groups. GSH and AChE activities did not show significant changes as compared with the FLU10 group. The CA3 and prefrontal cortex viable and degenerated neuron count in the FLU10 group were insignificant compared with all other groups, except for the NAR100 and NAR50 groups. Thus, Naringin can be a useful drug to avoid the neurological effects of fluoride.

Tao-Hong-Si-Wu-Tang Improves the Depressive-like Behaviors in Mice Experiencing Perimenopausal Depression Through Modulating Activity of the Hypothalamic-Pituitary-Adrenal-Ovary Axis and Activating the BDNF-TrkB-CREB Signaling Pathway.

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

Chronic defeat stress induces monoamine level dysregulation in the prefrontal cortex but not in the hippocampus of OF1 male mice

Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test (SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed, and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid, and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our results show that CSD induces differences in monoamine levels between brain areas, and these differences did not respond to the coping strategy adopted.

Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.

Adaptogenic action of diosgenin againsts chronic unpredictable mild stress-induced neuroimmune dysfunction of HPA axis reverses psychiatric behavior in mice

BackgroundStressful life experiences are associated with neurobehavioral abnormalities, such as anxiogenic-related depression and cognitive decline. Reportedly, adaptogens are well known to modulate stress-related responses and promote resilience. ObjectiveThis study aimed to assess the potential mechanisms and adaptogenic properties of diosgenin (DG), a phytosteroidal sapogenin with neuroendocrine protective effects, in chronic unpredictable mild stress (CUMS)-induced anxiogenic-depression and cognitive deficits in mice. MethodsDuring the 21-day study, mice were divided into five groups, and were daily treated with 5% dimethyl sulfoxide (control and CUMS model), diosgenin (25 mg/kg and 50 mg/kg) or fluoxetine (10 mg/kg) orally, respectively, followed by 21-item CUMS paradigm exposure, except for the control group. Mice were examined for anxiety, depression and cognitive-like features using relevant neurobehavioral paradigms. Biomarkers of oxidative stress, nitrite level, pro-inflammatory cytokines (TNF-α, IL-6), acetylcholinesterase (AChE), glutamic acid decarboxylase (GAD), and monoamine oxidase-B (MAOB) were measured in the prefrontal cortex, striatum, and hippocampal regions of the brain. Also, adrenal hypertrophy, serum corticosterone and glucose levels as a measure of hypothalamic pituitary adrenal (HPA) axis involvement were examined. ResultsDG ameliorated CUMS-induced behavioral anomaly, as characterized by the increased duration of grooming bouts in the sucrose preference test; decreased duration of immobility in the tail suspension and forced swim tests; anxiolytic effects in the elevated-plus maze, hole-board, light/dark compartment tests, as well as cognitive impairments indexed by the Y-maze and object recognition tests were reversed by DG respectively. DG remarkably decreased adrenal hypertrophy and elevated serum levels of corticosterone and glucose in CUMS mice. ConclusionConclusively, DG exhibits antidepressant-like and anxiolytic-like actions with memory enhancement in the CUMS mouse model, and thus could serve as an alternative agent for the management of depression and anxiety associated with cognitive decline in clinical settings.

Cheonwangbosimdan mitigates post-traumatic stress disorder-like behaviors through GluN2B-containing NMDA receptor antagonism in mice

Ethnopharmacological relevanceCheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects. Aim of the studyThe purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study. Materials and methodsA single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors. ResultsCWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction. ConclusionsCWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies.

A new mouse model of depression induced by chronic restraint stress combined with lipopolysaccharide

The aim of this study was to establish a multi-factor-induced depression model in mice within a relatively short period, specifically through the combination of intraperitoneal injection of lipopolysaccharide (LPS) and chronic restraint stress (CRS), and to evaluate the differences in depressive-like behaviors among three different strains of mice, seeking mouse strains more suitable for this combined model. The mice of each strain were randomly divided into the normal group and model group. The mice in the model group received a single intraperitoneal injection of LPS once daily (1 mg/kg/d for 7 days) and subsequent CRS for 6 h, to induce depression, while the mice in the normal group received no treatment. Behavioral tests: sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were conducted to assess depressive-like behaviors in the mice. Data analysis showed that there were significant intergroup differences in depressive-like behaviors in ICR and C57BL/6 J mice, while KM mice exhibited minor differences with relatively high deviation in individual behavioral score. This study indicated that the combined depression mouse model could successfully induce significant depressive-like behaviors in ICR and C57BL/6 J mice.

Concurrent exposure to light and traffic noise pollution augments behavioral deficits in rats: Protective effect of curcumin

The current study was aimed to explore the effect of light and traffic noise pollution exposure on behavioral and neurochemical deficits in adult male Wistar rats. We hypothesized that exposure to these pollutants alone or in combination may cause behavioral deficits in rats. Animals were allocated into different groups and were exposed to either varying light cycles (150 lx-5 lx, 14:10 h) or traffic noise with sound level 100 dBA for 6 h/day or both for 28 days. Concurrently, Curcumin (100 mg/kg; per oral; 28 days) was administered in varying light cycles and noise exposed animal groups to study the preventive effect. After the exposure time, the Morris water maze test, elevated plus maze test, novel object recognition test, locomotor activity test, and forced swimming test were conducted. The neurobehavioral results suggested that only combined exposure of light and noise pollution markedly impaired the learning as well as spatial and reference memory in rats. Furthermore, we found significant anxiety (less no. of open arm entries in EPM) and depressive-like behavior (increased immobility time) in light or/and traffic noise pollution exposed group animals in comparison to normal control groups. Curcumin treatment significantly prevented the behavioral anomalies in combined light and noise exposed rats. Furthermore, our results revealed augmentation of acetylcholinesterase, oxidative stress markers and interleukin (IL)-1β in the hippocampal region of noise and light-exposed groups which were markedly ameliorated by curcumin. In conclusion, our results suggest that curcumin significantly modulates light and noise pollution exposed behavioral and neurochemical anomalies in rats.

Chronic caffeine decreases anxiety-like behavior in the marble burying task in adolescent rats.

Exposure to chronic caffeine during adolescence has been shown to produce decreased anxiety-like behaviors in rats as well as decreased immobility in the forced swim test (FST) suggesting an antidepressant-like effect. The effects of chronic caffeine on anxiety, however, have been found to be test-dependent and sexually dimorphic. In addition, decreased immobility in the FST has been argued to reflect a shift toward active coping behavior as opposed to an antidepressant-like effect. In order to further characterize the effects of adolescent caffeine exposure, the present experiment assessed the effects of caffeine on marble burying behavior in a two-zone marble burying task. There was no difference in the amount of time rats spent in the two zones failing to support a shift in coping strategy. Caffeine-exposed rats spent less time engaged in marble burying activity and buried slightly fewer marbles, suggesting an anxiolytic effect of caffeine. In addition, caffeine treated rats spent less time engaged in nondirected burying and slightly more time actively engaging with the marbles; however, these effects appeared to be sexually dimorphic as they were driven by larger changes in the females. Overall, these results support an anxiolytic effect of adolescent caffeine, with female behavior appearing to be more affected by caffeine than males.

Sporoderm-removed Ganoderma lucidum spores ameliorated early depression-like behavior in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer's disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer's disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear. Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test. Results: Behavioral tests demonstrated that RGLS (360 and 720mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC. Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

Unraveling the molecular basis of cannabidiolic acid methyl Ester's anti-depressive effects in a rat model of treatment-resistant depression

Major depressive disorder (MDD) stands as a significant cause of disability globally. Cannabidiolic Acid-Methyl Ester (CBDA-ME) (EPM-301, HU-580), a derivative of Cannabidiol, demonstrates immediate antidepressant-like effects, yet it has undergone only minimal evaluation in psychopharmacology. Our goal was to investigate the behavioral and potential molecular mechanisms associated with the chronic oral administration of this compound in the Wistar Kyoto (WKY) genetic model of treatment-resistant depression. Male WKY rats were subjected to behavioral assessments before and after receiving chronic (14-day) oral doses of CBDA-ME (0.5 mg/kg), 15 mg/kg of imipramine or vehicle. At the end of the study, plasma corticosterone levels and mRNA expression of various genes in the medial Prefrontal Cortex and Hippocampus were measured. Behavioral outcomes from CBDA-ME treatment indicated an antidepressant-like effect similar to imipramine, as oral ingestion reduced immobility and increased swimming duration in the Forced Swim Test. Neither treatment influenced locomotion in the Open Field Test nor preference in the Saccharin Preference Test. The behavioral impact in WKY rats coincided with reduced corticosterone serum levels, upregulated mRNA expression of Cannabinoid receptor 1, Fatty Acid Amide Hydrolase, and Corticotropin-Releasing Hormone Receptor 1, alongside downregulation of the Serotonin Transporter in the hippocampus. Additionally, there was an upregulation of CB1 mRNA expression and downregulation of Brain-Derived Neurotrophic Factor in the mPFC. These findings contribute to our limited understanding of the antidepressant effects of CBDA-ME and shed light on its potential psychopharmacological mechanisms. This discovery opens up possibilities for utilizing cannabinoids in the treatment of major depressive disorder and related conditions.

Ciprofol ameliorates ECS-induced learning and memory impairment by modulating aerobic glycolysis in the hippocampus of depressive-like rats

Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats.

Anxiolytic and Antidepressant Effect of Phaseolus vulgaris on Animal Models.

An experimental study was conducted using rodents at different doses to evaluate the effect of Phaseolus vulgaris (red beans) on cage crossing, head dip, open field, elevated plus maze, and light and dark apparatus for anxiety and forced swim test for depression. The corticosterone level and histopathological evaluation was also done to correlate the antidepressive impact of the red beans. The study also identified the components responsible for the effect using GCMS. Based on the findings, red beans could be a potential non-pharmacological therapy for mild to moderate depressive patients. The anxiety model was conducted on mice weighing 20-25 gms. Group I was taken as control, group II as 500 mg/kg and group III as administered 1000 mg/kg. The tests were performed on 0th, 7th, 15th, 30th, 45th, and 60th day. The depression model research was conducted on albino rats weighing between 180 and 200 g, divided into four groups: a control group, a 500 mg/kg Phaseolus vulgaris group, a 1000 mg/kg Phaseolus vulgaris group, and a standard group treated with fluoxetine. The forced swimming test was performed on days 0, 7, 15, 30, 45, and 60, after which histopathological evaluations were conducted and blood samples were taken to assess corticosterone levels. GCMS was used to identify the constituents present in red beans, while optical spectroscopy was used to detect minerals and ions. Results showed that both doses of Phaseolus vulgaris possess anxiolytic effect and increased the struggling time of rats in depression model significantly, with the 1000 mg/kg dose showing more significant results than the 500 mg/kg dose. The GCMS results identified the presence of erucic acid, which causes an increase in α-amylase, thus reducing depression. Optical spectroscopy also showed that red beans contain zinc, which may increase BDNF and help in treating depression.

Evaluation of Ketamine after subacute low dosage Lipopolysaccharide-activated Microglia produced depressive-like phenotype in mice

Depression is a common mental illness, with an estimated 3.8% of global population affected. Peripheral administration of lipopolysaccharide (LPS) culminate in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in the forced swim test (FST) and anhedonia in sucrose preference tests (SPT). After 6 days of LPS stimulation, we established a depression model in C57BL/6 mice, where animals started to recover from the B/W loss brought on by the LPS and the significant immunological response that resulted in microglial activation in the brain. There was a modulation in the relative weight of the thymus and spleen observed under these experimental conditions. Ketamine having a quick onset of action reduces the emergence of depressive-like behaviour by modifying the intensity of Iba-1 in stressed mice by reducing swimming behaviour and boosting desire for sucrose. However, it did not result in an improvement in the number of microglia or CD11b cells activation in the hippocampus of C57BL/6 mice or in the relative weights of the spleen and thymus. In summary, these data emphasizes that Ketamine treatment improves depressive-like behavior and Iba-1 immunoreactivity, but the hyperactive in terms of number of microglia and CD11b expression were not modulated in the mouse hippocampus.

Replicating human characteristics: A promising animal model of central fatigue

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.

Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects. To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems. Male Swiss mice were treated with CF3SePB (1-50mg/kg, i.g.) and 30min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50mg/kg, i.g.), and after 30min of CF3SePB administration the FST was performed. CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice. This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation through modulation of cecal microbiota and enhanced butyric acid production.

The conversion of fast-twitch fibers into slow-twitch fibers within skeletal muscle plays a crucial role in improving physical stamina and safeguarding against metabolic disorders in individuals. Grape seed proanthocyanidin extract (GSPE) possesses numerous pharmacological and health advantages, effectively inhibiting the onset of chronic illnesses. However, there is a lack of research on the specific mechanisms by which GSPE influences muscle physiology and gut microbiota. This study aims to investigate the role of gut microbiota and their metabolites in GSPE regulation of skeletal muscle fiber type conversion. In this experiment, 54 male BALB/c mice were randomly divided into three groups: basal diet, basal diet supplemented with GSPE, and basal diet supplemented with GSPE and antibiotics. During the feeding period, glucose tolerance and forced swimming tests were performed. After euthanasia, samples of muscle and feces were collected for analysis. The results showed that GSPE increased the muscle mass and anti-fatigue capacity of the mice, as well as the expression of slow-twitch fibers. However, the beneficial effects of GSPE on skeletal muscle fibers disappeared after adding antibiotics to eliminate intestinal microorganisms, suggesting that GSPE may play a role by regulating intestinal microbial structure. In addition, GSPE increased the relative abundance of Blautia, Muribaculaceae, and Enterorhabdus, as well as butyrate production. Importantly, these gut microbes exhibited a significant positive correlation with the expression of slow-twitch muscle fibers. In conclusion, supplementation with GSPE can increase the levels of slow-twitch fibers by modulating the gut microbiota, consequently prolonging the duration of exercise before exhaustion. PRACTICAL APPLICATION: This research suggests that grape seed proanthocyanidin extract (GSPE) has potential applications in improving physical stamina and preventing metabolic disorders. By influencing the gut microbiota and increasing butyric acid production, GSPE contributes to the conversion of fast-twitch muscle fibers into slow-twitch fibers, thereby enhancing anti-fatigue capacity and exercise endurance. While further studies are needed, incorporating GSPE into dietary supplements or functional foods could support individuals seeking to optimize their exercise performance and overall metabolic health.

Investigating the synergistic effects of amitriptyline and H. pylori eradication on depressive-like behaviors and inflammatory cytokines in mice

BackgroundRecent research has highlighted the potential role of Helicobacter pylori in the pathogenesis of psychiatric disorders. This study aimed to evaluate the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in a mouse model. MethodsMale C57BL/6 mice were divided into four groups: control, H. pylori infection, antidepressant treatment, and combined treatment. H. pylori infection was induced by oral gavage with a clinically relevant strain, and the antidepressant drug was administered via intraperitoneal injections. Behavioral tests including the forced swim test, sucrose preference test, and open field test were conducted to assess depressive-like behaviors and locomotor activity. ResultsThe study demonstrated that H. pylori infection induced depressive-like behaviors in mice, as evidenced by increased immobility time in the forced swim test and reduced sucrose preference. Antidepressant treatment alone partially ameliorated these behavioral changes. Strikingly, the combined treatment of the antidepressant drug and H. pylori eradication therapy led to a significantly greater reduction in depressive-like behaviors compared to either treatment alone. Furthermore, the combined treatment group exhibited increased locomotor activity in the open field test, suggesting a potential improvement in overall psychomotor functioning. ELISA assays revealed alterations in inflammatory cytokines in the H. pylori-infected mice, which were partially attenuated by the combined treatment. ConclusionThe study provides novel evidence for the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in alleviating depressive-like behaviors in a mouse model.

Effect of Cryptotanshinone on BDNF/TrkB Pathway in Hippocampus of Chronic Stress-induced Depression Rats

Background: Cryptotanshinone (CTS) is a monomer possessing a diverse array of pharmacological properties, primarily derived from Salvia miltiorrhiza. CTS was examined for its impact on rats with depression subjected to chronic unpredictable mild stress (CUMS) in this study. Materials and methods: Depression-like behavior of rats was established by isolated feeding combined with CUMS for 28 days, with CTS (7/14/21 mg/kg) or fluoxetine (5 mg/kg) administered once daily during this time. A comprehensive evaluation was performed, including body weight assessment, sucrose preference test, forced swimming test, and open field test. Hematoxylin-eosin staining was conducted to detect pathological changes in hippocampal CA1 neurons. Western blot analysis was employed to assess the brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Cofilin expression levels in the hippocampus. Results: The depression rat model was successfully constructed. CTS can significantly improve impaired neurons in the hippocampal CA1 area, depression-like behaviors, and weight loss in CUMS-induced rats. Moreover, CTS reversed the down-regulation of BDNF/TrkB and Rac1/Cofilin in the CUMS-induced rats’ hippocampus. Conclusion: CTS demonstrates the therapeutic potential for depression by improving depression-like behaviors and ameliorating impaired neurons in the hippocampal CA1 area, and the mechanisms may involve the up-regulation of BDNF/TrkB and related signaling proteins Rac1/Cofilin.

Metronidazole-induced neurotoxicity: Possible central serotonergic and noradrenergic system involvement

Background: Metronidazole is a synthetic 5-nitroimidazole antibiotic. It remains a first-line therapy for anaerobic, parasitic, and bacterial infections in human and veterinary medicine. However, Metronidazole-induced neurotoxicity is a rising challenge. The mechanism of neurotoxicity induction is still unknown. Objective: To investigate a possible interference of metronidazole with central monoaminergic mechanisms using the Forced Swim Test. Methods: sixty adult rats were divided into 10 groups (n=10 for metronidazole and saline, n=5 for other groups). Group 1 = 5 ml/kg normal saline; Group 2 = 50 mg/kg metronidazole; group 3= 15 mg/kg imipramine; Group 4 =15 mg/kg imipramine + 50 mg/kg metronidazole. Group 5 = 5 mg/kg fluoxetine; Group 6 received 5 mg/kg fluoxetine + 50 mg/kg metronidazole; Group 7 = labetalol 10 mg/kg; Groups 8, 9 and 10 received labetalol 10 mg/kg + 50 mg/kg metronidazole, PCPA (p-chlorophenylalanine) 100 mg/kg and PCPA 100 mg/kg + 50 mg/kg metronidazole daily X 28 days. On day 28, FST was done 1h after the respective treatments. On day 29, blood samples were collected under halothane anesthesia for hematological assessment. Results: Immobility time increased (P&lt;0.01) in the groups treated with metronidazole, labetalol, PCPA, labetalol + metronidazole, and PCPA+ metronidazole. Swimming was reduced by metronidazole, PCPA, metronidazole + PCPA and metronidazole + labetalol. Metronidazole + labetalol reduced climbing. These effects were not reduced by co-treatment with imipramine or fluoxetine. White blood cell count increased (p&lt;0.01) in all treatment groups. Lymphocyte percent increased in the metronidazole-treated groups. Conclusion: Interference with postsynaptic central monoaminergic neurotransmission and immunomodulation may contribute to metronidazole-induced neurotoxicity.