Suspension Test Research Articles

Characterization of rice endosperm-derived antidepressant-like peptide (REAP): An orally active novel tridecapeptide derived from rice protein

It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8−13) but not REAP(1−7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130−142) and B5(130−142), in the digest. The effects of REAP were blocked by both dopamine D1 and D2 antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system.Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.

Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels.

Depression is a debilitating mood disorder affecting millions worldwide and continues to pose a significant global health burden. Due to the multifaceted nature of depression, the current treatment regimens are not up to mark in terms of their multitargeting potential and least side effect profile. Molecules within the isoflavone class demonstrate promising potential in alleviating depression and associated conditions, offering a multifaceted approach to manage mental health concerns. Therefore, the current study was designed to explore the potential of glycitein, an isoflavone in managing reserpine-induced depression and associated comorbidities in mice. Reserpine (0.5mg/kg; i.p.) administration for the first 3days induced depression and associated comorbidities as evidenced by increased immobility time in forced swim test (FST) and tail suspension test (TST), along with reduced locomotor activity in the open field test (OFT) and increased latency to reach the platform in the Morris water maze (MWM) test. Reserpine treatment also upregulated and downregulated the brain thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) levels, respectively. Furthermore, reserpine administration also uplifted the level of TNF-α in the serum samples. Glycitein (3mg/kg and 6mg/kg; p.o.) treatment for 5days prevented the depressive effect of reserpine. It also improved the spatial memory at both dose levels. Moreover, in biochemical analysis, glycitein also reduced the brain TBARS and serum tumor necrosis factor-alpha (TNF-α) levels. Whereas, no significant effect was seen on the brain GSH level. Glycitein (6mg/kg) was found to be more effective than the 3mg/kg dose of glycitein. Overall results delineate that glycitein has the potential to manage depression and impaired memory by inhibiting lipid peroxidation and inflammatory stress.

Quercetin attenuates brain apoptosis in mice with chronic unpredictable mild stress-induced depression

BackgroundDepression is a common psychiatric disorder with limited effective treatments. Research suggests that depression involves apoptosis mechanisms. Quercetin (QUE) has been reported to have anti-apoptotic activities. In this study, we aimed to investigate the effects and mechanisms of QUE in chronic unpredictable mild stress (CUMS)-induced depression. MethodsAfter establishing mouse models of CUMS-induced depression, the mice were randomly assigned into four groups: control, CUMS, CUMS+QUE, and CUMS+Fluoxetine (FLX). The body weight of the mice was measured during the study. Then, depression-associated behaviors were evaluated using the sucrose preference test (SPT), novelty suppressed feeding test (NSFT), forced swim test (FST) and tail suspension test (TST). Apoptosis in the hippocampus and prefrontal cortex was determined using flow cytometry. Bcl-2 and Nrf2 protein expressions in the hippocampus and prefrontal cortex were also detected. Furthermore, Western blot was used to measure the protein levels of p-ERK, ERK, p-CREB, CREB, and Nrf2 in brain tissues. ResultsQUE or FLX administration increased the body weight of the CUMS mice. Behavioral tests indicated that CUMS mice developed a state of depression, but QUE or FLX treatment improved their depression-associated behaviors. Meanwhile, QUE or FLX treatment decreased apoptosis in the hippocampus and prefrontal cortex. Furthermore, the decreased Nrf2 protein expression, ERK and CREB phosphorylation in CUMS group were enhanced by QUE or FLX administration. ConclusionQUE could attenuate brain apoptosis in mice with CUMS-induced depression, and the mechanism may be related to the ERK/Nrf2 pathway, indicating that QUE could be a potential treatment for depression.

A comprehensive approach for evaluating the virucidal performance of domestic laundry detergents under practical conditions.

We aimed to develop a method to assess the virucidal performance of domestic laundry in a lab-scale washing machine (Rotawash) based on EN 17658. For method development, virus recovery was investigated after drying on cotton carriers for three test viruses murine norovirus (MNV), modified vaccinia virus Ankara (MVA), and bovine coronavirus (BCoV), followed by washing simulations in flasks and Rotawash. MNV and MVA demonstrated sufficient recovery from carriers after drying and washing (up to 40°C and 60min). BCoV exhibited lower recovery, indicating less relevance as a test virus. Rotawash efficacy tests conducted with MNV, a resistant, non-enveloped virus, showed limited efficacy of a bleach-free detergent, aligning with results from a domestic washing machine. Rotawash washes achieved higher reductions in infectious virus titers than suspension tests, indicating the role of washing mechanics in virus removal. This study established a practical method to test the virucidal efficacy of laundry detergents in Rotawash, simulating domestic washing.

A soy protein enzymatic digest mitigates Nrf2-related oxidative stress and attenuates depression-like behavior in a mouse model of sub-chronic restraint stress

Continuous oxidative stress conditions have been identified as a major cause of various neuropsychiatric disorders, including depression. The present study investigated the potential antidepressant-like effects of a soy protein enzymatic digest (SPD) containing soy-deprestatin, which is a soy-derived peptide with reported antidepressant-like effects, as well as its ability to mitigate oxidative stress in the brain caused by sub-chronic restraint stress. Mice were divided into two groups: a control group and restraint stress group. The restraint stress group was further divided into two groups administered water or SPD. After repeated short-time restraints over five days, we evaluated immobility times in the tail suspension test, and antioxidant enzyme activities, glutathione levels, oxidative stress maker levels, and the gene expression levels of Nrf2 and antioxidant enzymes in the brain. The results obtained showed that the oral administration of SPD reduced immobility times in mice exposed to restraint stress. In comparisons with the water-treated restraint group, the administration of SPD restored superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione levels and prevented restraint stress-induced increases in malondialdehyde, carbonyl protein, and 8-OHdG levels in the restraint stress group. In addition, high expression levels of Nrf2, HO-1, NQO-1 and GCLC were observed in the SPD-treated restraint group. These results suggest that SPD attenuated repeated restraint stress-induced depression-like behaviors by mitigating oxidative stress through the activation of the Nrf2 signaling pathway.

Gamma-Aminobutyric Acid in Rice Bran Extract Exerts Antistress Effects in Mouse Models with Depressive-Like Behaviors.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3mg/kg dulaglutide group (Low Dula group), and a CMS+0.6mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 μM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.

Nutritional ketosis as treatment for alcohol withdrawal symptoms in female C57BL/6J mice

Upon both acute and prolonged alcohol intake, the brain undergoes a metabolic shift associated with increased acetate metabolism and reduced glucose metabolism, which persists during abstinence, putatively leading to energy depletion in the brain. This study evaluates the efficacy of ketogenic treatments to rescue psychiatric and neurochemical alterations during long-term alcohol withdrawal. Female mice were intermittently exposed to alcohol vapor or air for three weeks, during which mice were introduced to either a ketogenic diet (KD), control diet supplemented with ketone ester (KE) or remained on control diet (CD). Withdrawal symptoms were assessed over a period of four weeks followed by re-exposure using several behavioral and biochemical tests. Alcohol-exposed mice fed CD displayed long-lasting depressive-like symptoms measured by saccharin preference and tail suspension, as well as decreased norepinephrine levels and serotonin turnover in the hippocampus. Both KD and KE rescued anhedonia for up to three weeks of abstinence. KD mice showed higher latency to first immobility in the tail suspension test, as well as lower plasma cholesterol levels. Our findings show promising effects of nutritional ketosis in ameliorating alcohol withdrawal symptoms in mice. KD seemed to better rescue these symptoms compared to KE.

Permanent Magnet Electrodynamic Suspension System Integrated With a Car: Design, Implementation, and Test

In this paper, a permanent magnet electrodynamic suspension (PMEDS) system integrated with a car has been developed by our group, along with a 100-m-long test track made of copper. The entire vehicle weighs 2.8 ton and is freely suspended in air over 35 mm without a lateral constraint on guideway. The car uses its own wheels and engine to provide a take-off speed for the PMEDS system, eliminating the excessive costs of the motor, with a maximum speed of 70 km/h. Firstly, a new topology structure equipped with the damping magnets is presented. Afterward, the onboard magnets and guideway are designed via the simulation method verified by the high-speed rotary experiment platform with a diameter of 2500 mm, clarifying the mapping between the electromagnetic forces and structure parameters. The suspension frame and gap adjustment mechanism are developed, and a complete test system is built to monitor the levitation gap, accelerations and deflection angle. Lastly, the integrated PMEDS system is implemented and tested. In-house experiment and line test results not only reveal that the PMEDS has a significant weak guidance capability, but also confirm the effectiveness of the proposed damping magnets. Through the damping magnets, the maximum lateral deflection is limited to less than 11°. The tested levitation-drag-ratio is in general agreement with the simulation results. The great suspension capacity of the PMEDS system can be visually demonstrated. This paper conducts the free suspension test of the PMEDS system for the first time in China, which can open up prospects for further engineering applications.

Gynura procumbens and selected metabolites: Amelioration of depressive-like behaviors in mice and risperidone-induced hyperprolactinemia in rats

Gynura procumbens (Lour.) Merr., utilized in traditional Chinese medicine, is known for its liver-protective, liver-soothing, and depression-alleviating properties. This research examines the antidepressant and anti-hyperprolactinemia potentials of an ethanol extract from G. procumbens stems (EEGS) and specific metabolites. To model depression and hyperprolactinemia, chronic unpredictable mild stress (CUMS) was induced in mice and risperidone was administered to rats, respectively. Treatments involved administering low (5 mg/kg), medium (25 mg/kg), and high (125 mg/kg) doses of EEGS and certain metabolites to both models. Behavioral assessments were conducted in the CUMS-induced mice, while the CA3 neuronal damage in mice and histopathological alterations in rat mammary glands were evaluated using Nissl and Hematoxylin & Eosin staining techniques, respectively. EEGS decreased immobility times in the forced swimming and tail suspension tests in mice, enhancing their exploration of the central zone. It elevated the serum levels of 5-hydroxytryptamine, norepinephrine, estradiol, luteinizing hormone (LH), and testosterone in mice. Moreover, EEGS restored the neuronal cell arrangement in the CA3 area, reduced interleukin-1beta mRNA production, and increased the expression of interleukin-10 and beta-catenin mRNA. In the context of risperidone-induced hyperprolactinemia, EEGS lowered blood prolactin levels, reduced the dimensions of rat nipples, and enhanced LH, progesterone, and dopamine levels, alongside mitigating mammary hyperplasia. Among the EEGS selected metabolites, the combined effect of chlorogenic acid and trans-p-coumaric acid was found to be more effective than the action of each compound in isolation. Collectively, the findings indicate that EEGS and its selected metabolites offer promising antidepressant benefits while counteracting hyperprolactinemia.

Methanol leaf extract of Leptadenia hastata ameliorates chronic, unpredictable, mild stress-induced depression

Leptadenia hastata (Pers) Decne is a tropical herb widely used in the phytotherapy of neuropsychiatric disorders, including depression. Despite the availability of synthetic antidepressant drugs, depression remains a major medical problem. The study aimed to evaluate the effect of methanol leaf extract of Leptadenia hastata (LHME) on chronic unpredictable mild stress-induced depression. Acute toxicity of Leptadenia hastata was determined using Organization for Economic Co-operation and Development (OECD) guidelines. The chronic unpredictable mild stress (CUMS) model-induced depression involves the evaluation of baseline behavioural changes in the sucrose preference test, open field test, and tail suspension test. The brain-derived neurotrophic factor (BDNF) concentrations and serum cortisol were assessed using an enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were also assessed using standard procedure. The median lethal dose (LD50) value was > 5000 mg/kg. LHME at doses of 250 – 1000 mg significantly (p<0.01) decreased CUMS-induced depression in a dose-dependent manner. LHME significantly (p<0.01) reversed depression associated weight loss from 14.00±0.62 g in week two to 22.57±1.13 g in week five of the experiment. It also increased sucrose consumption in the sucrose preference test (SPT) from 4.29±0.52 ml in week two to 9.71±0.68 ml in week five. The LHME also significantly (p<0.01) decreased the duration of immobility from 190.00±4.55 sec in week two to 158.00±3.83 sec in week five in the tail suspension test (TST). Furthermore, LHME at the tested dose significantly (p<0.01) increased the locomotor activity from 36.29±1.25 sec in week two to 62.43±1.73 sec in week five in the open field test (OFT). LHME significantly (p<0.01) and dose-dependently increased the levels of BDNF (204.74±22.97 pg/ml) and decreased the levels of plasma cortisol (0.98±0.06 ng/ml). However, treatment with LHME and the standard drug imipramine did not significantly change SOD activity and the MDA level in CUMS-induced mice. The findings demonstrated that LHME ameliorates CUMS-induced depressive-like behaviours, and its effect is possibly mediated via the neuroendocrine (cortisol) and neurotrophic (BDNF).

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential μ−opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective μ−opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ−opioid receptor antagonist, norbinaltorphimine, we demonstrate that μ−opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ−opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.

Bambusa vulgaris attenuates Haloperidol-induced motor deficit and non-Motor co-morbidity in rats through up-regulation of Dopamine transmission and mitigation of pro-inflammatory cytokines activities

BackgroundBamboo is a plant widely distributed in many parts of the world and grows in about 18 provinces in China. One of the species of the plant is Bambusa vulgaris. An ethnobotanical survey of the plant revealed its values in managing neurodegenerative diseases, including Parkinson's disease. ObjectiveThis study examined the effect of hydroethanolic leaf extract of Bambusa vulgaris (BVE) on motor functions and non-motor co-morbidity, dopamine content, pro-inflammatory cytokines and oxidative species in haloperidol-treated rats. MethodsRats were pretreated with distilled water (10 mL/kg), B. vulgaris extract (100, 200 and 400 mg/kg) and levodopa-carbidopa (LD-CD; 25/100 mg/kg, orally). Precisely one hour post every treatment, haloperidol (2 mg/kg, i.p) was administered to the rats across all groups every 48 h for 21 days. Motor and non-motor functions were assessed on day 22. After that, brains were removed and processed for dopamine content evaluation, pro-inflammatory cytokines determination, oxidative damage assessment and histopathological examinations of the striatum and substantia nigra. ResultsB. vulgaris increased (P < 0.01; 400 mg/kg) the distance covered and decreased the frequency foot slips (P < 0.01, 0.001; 200–400 mg/kg) in the beam work test; decreased (P < 0.05–0.0001; 100–400 mg/kg) the catalepsy behavior in the catalepsy bar test; reversed hypo-locomotor activity (P < 0.0001; 400 mg/kg) in open field test; and decreased (P < 0.05–0.001; 100–400 mg/kg) the non-motor behavioural deficit in tail suspension test. BVE increased (P < 0.01; 200 mg/kg) dopamine concentration in the brain and decreased TNF-α (P < 0.05; 200 mg/kg) and IL-6 (P < 0.01, 0.001; 100–400 mg/kg) concentrations in the brain. BVE significantly increased the GSH (P < 0.05, 0.001; 100–200 mg/kg) and Catalase (P < 0.05, 0.01; 100–400 mg/kg) levels and decreased the MDA level (P < 0.05, 0.01; 200–400 mg/kg) in the brain tissue. ConclusionOur findings suggest that the hydroethanol leaf extract of Bambusa vulgaris reverses the haloperidol-induced motor deficits and non-motor co-morbidity by mitigating the pathophysiological abnormalities associated with the progression of the disease. Based on these outcomes, the peak effect was observed at 200 mg/kg.

Prebiotics modulate the microbiota–gut–brain axis and ameliorate anxiety and depression-like behavior in HFD-fed mice

Previous research has demonstrated that Prebiotics can influence the composition of the gut microbiota, consequently impacting mood regulation. This study aimed to assess the effects of Prebiotics, specifically Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on neuroinflammation, depression, and anxiety-like behavior in a mouse model fed a high-fat diet (HFD). Initially, mice were divided into two groups: a control group on a standard diet (n = 15) and a group on an HFD for 18 weeks (n = 45). By the 13th week, the HFD group was further divided into experimental groups: Control (n = 15), HFD (n = 15), HFD receiving Prebiotics (n = 15), and HFD receiving Fluoxetine (n = 15). From the 13th week onward, the HFD + Prebiotics group received both the high-fat diet and a combination of FOS and GOS, while the HFD + Fluoxetine group received Fluoxetine in their drinking water. In the 18th week, all mice underwent tests to evaluate behavior, including the Tail Suspension Test (TST), Forced Swimming Test (FST), Sucrose Preference Test (SPT), and the Plus Maze Test (PMT), after which they were euthanized. Mice on the HFD exhibited increased body weight, abdominal size, blood glucose, triglyceride levels, cholesterol, insulin, HOMA index, and higher serum IL-1β. These obese mice also displayed an increased number of microglia and astrocytes, activation of the TLR4 pathway, and elevated levels of neuroinflammatory markers like TNF-α, IL-1β, and COX-2. Moreover, obese mice showed increased activation of the IDO pathway and decreased levels of NMDA receptors. Additionally, markers of neurogenesis and synaptic plasticity, such as PSD, SAP 102, CREB-p, and BDNF, were lower. Treatment with FOS and GOS reversed symptoms of depression and anxiety in mice subjected to HD. This improvement in behavior resulted from a reduction in dysbiosis with an increase in acetate-producing bacteria (B. acidifaciens and B. dorei) and intestinal permeability, leading to a decrease in chronic peripheral and central inflammation. Furthermore, the modulation of the gut-brain axis by FOS and GOS promoted elevated acetate and GPR43 levels in the brain and a reduction in the levels of pro-inflammatory cytokines, positively impacting signaling pathways of neuronal proliferation and survival in the hippocampus and prefrontal cortex.

Targeting Large-Conductance Calcium-Activated Potassium Channels to Ameliorate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.

Neuroinflammation plays crucial role in the development and progression of depression. Large conductance calcium- and voltage-dependent potassium (BK) channels mediate the activation of microglia. Herein, we investigated whether BK channels could serve as a target for the treatment of inflammation-associated depression. Lipopolysaccharide (LPS, 0.83mg/kg) was injected intraperitoneally (i.p.) to induce neuroinflammation and depressive-like behavior in 6-8week ICR mice. Adeno-associated virus (AAV) constructs (AAV9-Iba1p-BK shRNA-EGFP (BK shRNA-AAV) or AAV9-Iba1p-NC shRNA-EGFP (NC shRNA-AAV)) were unilaterally injected intracerebroventricularly to selectively knock down BK channels in microglia. The tail suspension test (TST) and forced-swim test (FST) were used to evaluate depressive-like behavior in mice 24h after LPS challenge. The morphology of microglia, expression of BK channels, levels of cytokines, and expression and activity of indoleamine 2,3-dioxygenase (IDO) were measured by immunohistochemistry, western blot, quantitative real time PCR, and enzyme-linked immunosorbent assay (ELISA), respectively. Either paxilline (i.p.), a specific BK channel blocker, or BK shRNA-AAV effectively inhibited the activation of microglia, reduced the production of IL-1β in the hippocampus and suppressed the expression and activity of IDO in the hippocampus and prefrontal cortex, resulting in the amelioration of depressive-like behavior in mice. These data suggest for the first time that BK channels are involved in LPS-induced depressive-like behaviors. Thus, microglia BK channels may be a potential drug target for the depression treatment.

Synergistic antidepressant-like effect of citicoline and CB 1 agonist in male mice.

The endocannabinoid system plays a key role in the control of many emotional-correlated reactions such as stress, depressed mood, and anxiety. Moreover, citicoline has neuroprotective properties and indicates beneficial effects in the treatment of depressive problems. Acute restraint stress (ARS) is an experimental model used for the induction of rodent models of depression. This research was designed to assess the effects of intracerebroventricular (i.c.v.) injection of cannabinoid CB1 receptor agents on citicoline-induced response to depression-like behaviors in the non-acute restraint stress (NARS) and ARS mice. For i.c.v. microinjection, a guide cannula was implanted in the left lateral ventricle of male mice. The ARS model was carried out by movement restraint for 4 h. Depression-related behaviors were assessed by forced swimming test (FST), tail suspension test (TST), and splash test. The results exhibited that the ARS mice showed depressive-like responses. I.c.v. infusion of ACPA (1 μg/mouse) induced an antidepressant-like effect in the NARS and ARS mice by reduction of immobility time in the FST and TST as well as enhancement of grooming activity time in the splash test. On the other hand, i.c.v. microinjection of AM251 dose-dependently (0.5 and 1 μg/mouse) induced a depressant-like effect in the NARS mice. I.p. injection of citicoline (80 mg/kg) induced an antidepressant-like response in the NARS and ARS mice. Furthermore, ACPA (0.25 μg/mouse, i.c.v.) potentiated the antidepressant-like response induced by citicoline (20 mg/kg, i.p.) in the NARS and ARS mice. However, AM251 (0.25 μg/mouse, i.c.v.) reversed the antidepressant-like effect produced by the citicoline (80 mg/kg, i.p.) in the NARS and ARS mice. Interestingly, our results indicated a synergistic effect between citicoline and ACPA based on the induction of an antidepressant-like effect in the NARS and ARS mice. These results suggested an interaction between citicoline and cannabinoid CB1 receptors on the modulation of depression-like behaviors in the NARS and ARS mice.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

Pharmacological Investigation of Pithecellobium dulce Stem Bark extract for Anti-Depressant Activity on Mice and Rats

Pithecellobium dulce (PD), commonly known as Jangli-jilebi, is a Manila tamarind belonging to the family Leguminosae. P. dulce (PD) is used to treat various diseases like diarrhea, asthma, leprosy, paralysis, inflammatory, anti-bacterial, spermicidal, anti-convulsant, etc. In this paper, we studied the activity of P. Dulce for depression, which is a debilitating, life-threatening, and common disease affecting different sections of the community. Chemical and synthetic medications used to treat this disease have significant negative side effects, and only 50–60% of patients fully recover. At the same time, the available scientific information about this species is scarce, and there are no reports related to its possible effects on the central nervous system. In this work, the effects of acetone and methanolic extracts of the stem bark of P. dulce (PD) were evaluated in mice and rats utilizing behavioral assays sensitive to clinically effective anti-depressant compounds. In both the forced swim test and the tail suspension test, the extracts (100 and 200 mg/kg) administered orally were able to shorten the immobility duration of mice and rats in a dose-dependent manner. According to the current study's findings, PD extract may have antidepressant potential and be useful in treating those who suffer from depressive disorders. These findings proved that PD has specifically anti-depressive in vivo effects.