Search Results (716)

Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of this study was to evaluate the anxiolytic and/or antidepressant-like effects of P. cubensis mushroom aqueous extract (PcAE) microdosing in mice using open-field and rota-rod tests, followed by plus-maze or forced swimming tests. We also evaluated changes in neuronal activity and dendritic maturation using electrocorticography (ECoG) and immunohistochemical techniques. The outcomes were compared with an effective macrodose of PcAE and antidepressant fluoxetine (FLX). For this study, mice were grouped as follows: (1) vehicle, (2) acute, and (3) repeated (10 days) PcAE microdosing (1 µg/kg); (4) single PcAE macrodose (1 g/kg); and (5) acute and (6) repeated reference drug fluoxetine (FLX, 10 mg/kg).The anxiolytic and antidepressant-like effects using microdosing were similar to those observed with macrodoses of PcAE and FLX; significant dose- and/or time-dependent changes in the ECoG and dendritic maturation of hippocampus neurons were also observed, in addition to altered corticosterone levels. To conclude, P. cubensis mushroom promotes brain effects in mice after micro- and macrodosing, supporting its potential as a therapeutic alternative for mental health. Full article

As a representative form of extreme weather, typhoons inflict widespread and systemic damage, posing a severe threat to the livestock industry. The stress they induce, typhoon stress (TS), is an unavoidable and complex environmental challenge that severely disrupts the ovarian function of Wenchang chickens. In this preliminary study, we employed a two-group comparison design (n = 6 per group) integrating behavioral observations, serum biochemical assays, histopathological examinations, and molecular analyses (qPCR, 16S rDNA sequencing, and transcriptome sequencing) to explore the role of the microbiota–gut–brain–ovarian axis (MGBOA) in this process. The findings revealed that TS markedly reduced water intake and locomotor activity, while it elevated serum corticosterone (CORT) and oxidative stress markers. It also induced shifts in gut microbiota composition, including a decrease in Bacteroides and an increase in Escherichia–Shigella. Furthermore, TS compromises duodenal intestinal barrier integrity, as evidenced by downregulation of the tight junction proteins TJP1 and CLDN1, structural damage to intestinal villi, and a reduced villus-to-crypt ratio. In the hypothalamus, VIP mRNA expression was upregulated, while GHSR expression was downregulated; the expression of the tight junction protein CLDN5 was also reduced. In the ovary, reproductive potential was suppressed, manifested by a reduction in follicle number and downregulation of STAR expression. Ovarian transcriptome analysis highlighted enrichments in pathways associated with inflammation (e.g., Toll-like receptor signaling) and lipid metabolism (e.g., PPAR signaling). These results support the hypothesis that TS impairs egg production via the MGBOA, providing preliminary mechanistic insights into how environmental stressors might disrupt animal productivity through MGBOA-mediated pathways. Full article

In vertebrates, corticosterone and cortisol are glucocorticoid (GC) steroid hormones central to the vertebrate stress response, but their relative contribution depends on context and life history. We used water-borne hormone sampling in lesser sirens, Siren intermedia, to examine whether corticosterone or cortisol predominates in stress responses and evaluated whether dermal secretions reliably track acute corticosterone changes. First, we measured corticosterone via dermal swabbing over a 2 h period following a hand-restraint stressor. Dermal corticosterone did not increase relative to pre-stressor baseline levels during the 2 h sampling period, suggesting that dermal measurements may not reflect acute circulating GC changes. We then measured cortisol and corticosterone across the GC profile (baseline, stressed, and recovery) using water-borne sampling techniques in juveniles. Cortisol release rates were significantly higher than corticosterone and were elevated during the recovery phase relative to baseline (p = 0.08), whereas stressed samples did not differ from baseline. Additionally, cortisol release rates were positively associated with temperature, while no effect of temperature was detected on corticosterone. Although cortisol and corticosterone were strongly correlated, cortisol responded to environmental temperatures and was repeatable, whereas corticosterone was not. Finally, we validated the use of water-borne sampling techniques to measure cortisol and corticosterone in S. intermedia. Cortisol was higher in juvenile sirens, highlighting that each GC may play functionally distinct roles across contexts. Together, these findings indicate that cortisol is the more environmentally responsive GC in juvenile S. intermedia and that water-borne sampling provides a more reliable method for assessing acute stress physiology in this species. Full article

This study investigated whether tongue motor loss induced by bilateral transection of the hypoglossal nerves (Hx) alters anxiety- and/or depression-like behaviors in rats and examined the associated neuroendocrine changes. Male Sprague–Dawley rats underwent Hx or sham surgery and were evaluated in the ambulatory activity, elevated plus maze, forced swim, and sucrose preference tests at different postoperative time points. Neuroendocrine parameters were assessed by plasma corticosterone assay, quantitative real-time PCR, Western blot analysis, and adrenal histology. At two weeks after surgery, Hx rats exhibited anxiety-like behavioral changes in the elevated plus maze and increased immobility with reduced struggling in the forced swim test, consistent with a depression-like behavior. Reduced sucrose intake was observed at earlier postoperative stages, suggesting early anhedonia-like behavior. Hx rats also showed chronically increased plasma corticosterone levels, adrenocortical hypertrophy, and decreased hippocampal glucocorticoid receptor expression. These findings highlight a potential oral–systemic interaction in which loss of oral motor function alters neuroendocrine homeostasis and emotional regulation. Full article

Methionine (Met), an essential amino acid involved in antioxidant defense and immune regulation in all vertebrates, may play a critical role in modulating acute immune stress responses; however, whether methionine reduction or supplementation in broilers is more beneficial during acute immune challenge remains unclear. To address this gap, this study compared the effects of dietary methionine reduction and supplementation on growth performance, antioxidant status, immune responses, and methionine metabolism in broilers subjected to lipopolysaccharide (LPS) challenge. In total, 504 one-day-old male broilers were assigned to four treatment groups: control (CON, 0.55%, marked as 100%Met), lipopolysaccharide-challenged (LPS, 0.55%, marked as 100%Met), methionine-restricted with LPS challenge (MR + LPS, 0.35%, marked as 60%Met), and methionine-supplemented with LPS challenge (MS + LPS, 0.75%, marked as 140%Met) groups. The experiment lasted for 21 days. On days 17, 19, and 21, broilers in the LPS-stimulated groups received intraperitoneal injections of LPS at 1 mg/kg body weight. Methionine restriction increased the feed conversion ratio before challenge, whereas average daily gain decreased in both LPS and MS + LPS groups during the challenge. Serum alanine aminotransferase, aspartate transaminase, LPS, corticosterone, interleukin-1β, interleukin-6, tumor necrosis factor-α, and hepatic malondialdehyde levels were reduced in the MR + LPS group compared with the LPS group (p < 0.05), whereas interleukin-10, antioxidant enzyme activities, total antioxidant capacity, and hepatic expression of antioxidant- and sulfur-metabolism-related genes were increased (p < 0.05). These findings indicate that moderate methionine restriction during acute immune stress enhances antioxidant capacity, alleviates hepatic burden, and supports metabolic stability in broilers. Full article

Non-motor symptoms of PD impair quality of life and remain challenging to treat. Here, we examined the effects of short- (38 days) and long-term (178 days) supplementation with the natural polyamine spermidine on anhedonia and anxiety-like behaviours in a 6-hydroxydopamine-induced rat model of PD and linked them with spermidine’s anti-inflammatory properties. Behavioural assessments (cylinder, sucrose preference, elevated plus-maze tests) were conducted during progressive neurodegeneration and after oral treatment. Under the same conditions, peripheral inflammation was evaluated by the total leukocytes and their subpopulation numbers (hematological analysis) and by CD4⁺ and CD8⁺ T lymphocyte percentages (imaging flow cytometry); the plasma levels of interleukins 4 and 10 and corticosterone (enzyme-linked immunosorbent assay) were also evaluated. The safety of long-term supplementation was assessed using standard biochemical markers (chemistry analyser). Both treatment regimens reversed 6-hydroxydopamine-induced lymphopenia. Long-term spermidine treatment increased the number of TCD4⁺ lymphocytes and monocytes and elevated the plasma concentrations of IL-4 and IL-10, while reducing corticosterone levels. These immunomodulatory effects were associated with reduced anhedonia and anxiety. All of the biochemical safety parameters remained within normal ranges. Spermidine alleviates neuropsychiatric symptoms in a rat model of progressive neurodegeneration in the nigrostriatal system through its regulatory influence on peripheral immune responses. Exploring the systemic mechanisms underlying spermidine’s effects could unveil innovative supplementation strategies and expand treatment options for managing symptoms in PD. Full article

Background: Chronic unpredictable stress triggers various pathological and metabolic alterations by modulating psychophysiological balance. Valeric acid (VA), a postbiotic material, has been reported to mitigate stress-induced behavioral changes in rodents. Objectives: To investigate the protective effect of valeric acid against chronic unpredictable stress in a rodent model by assessing neuro-physiological alterations along with changes in biochemical parameters to confirm the possible mechanism. Methods: A 14-day chronic unpredictable stress (CUS) model in albino Wistar rats was developed to check the stress-induced changes using forced swim test, tail suspension test and sexual behavior observation. Quantification of IL-6, TNF-α, IL-1β, plasma corticosterone level and oxidative stress parameters were also done. Results: Findings revealed the protective effects of valeric acid against CUS, which reversed the depression caused by a forced swim and tail suspension test in rats. Proinflammatory and oxidative stress markers were significantly (p < 0.05) restored in CUS rats treated with valeric acid as compared with the vehicle control, which was comparable to the standard drug, Panax ginseng. Conclusions: The present study concludes that valeric acid demonstrated significant (p < 0.05) anti-stress effect by modulating both behavioral responses and stress-related biochemical modifications. Full article

We conducted this experiment with the aim of investigating the effects of different noise levels from ventilation fans on the growth and slaughter performance, meat quality, blood parameters, and feeding behavior of geese from 21 to 70 days of age. A total of 108 male geese (21-day-old) were randomly assigned to one of three conditions: a control group (no additional fan noise), low-noise treatment (65–75 dB), and high-noise treatment (85–95 dB). Each treatment included six replicates, with six geese per replicate. The results showed that neither ventilation fan noise level significantly affected growth performance, feeding behavior, slaughter performance, or major meat quality traits (p > 0.05). Compared with the control group, noise exposure significantly reduced circulating adrenocorticotropic hormone and corticosterone concentrations (p < 0.05), and the low-noise group exhibited significantly reduced cortisol concentrations (p < 0.05), while the high-noise group had increased cortisol concentrations. Under noise exposure conditions, no statistically significant effects were observed on superoxide dismutase, total antioxidant capacity, malondialdehyde concentration, catalase, and glutathione peroxidase activities compared with the control group (p > 0.05). Overall, prolonged noise stimulation (65–75 dB and 85–95 dB) alleviated stress responses in commercial geese aged 21–70 days, without negatively affecting their growth performance, slaughter performance, meat quality, or feeding behavior. Full article

Background: Posttraumatic stress disorder (PTSD) is a mental illness in which central stress-regulating regions, including locus coeruleus (LC) and paraventricular nucleus of hypothalamus (PVN), play key roles. Clonidine, a central sympatholytic drug, can inhibit LC activity and reduce PTSD-related symptoms, suggesting noradrenergic involvement. Glia-driven immune mechanisms may link LC activity to PVN responses. Since TRPA1 ion channel is implicated in both neuroinflammation and stress adaptation, we aimed to determine whether its presence modulates the function of brain structures contributing to PTSD-related alteration in central stress adaptation. Methods: Foot shock PTSD model was applied to Trpa1 wild-type (WT) and knockout (KO) mice, and outcomes were assessed four weeks later. Immunohistochemistry was used to evaluate tyrosine hydroxylase (TH) levels in the LC and glial activation in the PVN. Behavioral effects of clonidine and circulating corticosterone levels were also examined. Results: Stress increased LC/TH immunoreactivity and PVN glial activation. Trpa1 deletion exaggerated LC/TH responses but reduced PVN astrocyte activation. Clonidine increased freezing and decreased jumping (a hyperarousal marker). KO mice showed enhanced jumping and did not respond to clonidine. Corticosterone levels remained unchanged. Conclusions: TRPA1 may support stress adaptation in PTSD by regulating LC noradrenergic output and PVN neuroinflammation, independently of α₂-adrenergic signaling. Full article

Aim: This study investigated the synergistic therapeutic effects and underlying mechanisms of tetrahydroberberine (THB) combined with protopanaxadiol (PPD) on p-chlorophenylalanine (PCPA)-induced insomnia in rats. Methods: Rats were randomly divided into normal, model, diazepam, THB monotherapy, PPD monotherapy, and THB + PPD combination groups. Evaluations included the pentobarbital sleep test, HE staining, ELISA, 16S rRNA sequencing, metabolomics, and Western blot. Results: Results demonstrated that the THB + PPD combination exhibited significant synergistic effects compared with monotherapies: the combination shortened sleep latency by 56.2% (vs. 44.2% for THB alone and 20.7% for PPD alone) and prolonged sleep duration by 112.8% (vs. 70.2% for THB and 59.6% for PPD) relative to the model group, while effectively restoring body weight gain. Histologically, combined treatment significantly alleviated hippocampal neuronal damage and increased the number of intact neurons in the dentate gyrus. Molecularly, it upregulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels, restored neurotransmitter balance (serotonin, dopamine, and glutamate), suppressed overactivation of the hypothalamic–pituitary–adrenal (HPA) axis (reducing corticotropin-releasing hormone and corticosterone), and decreased pro-inflammatory cytokine expression. Gut microbiota analysis revealed that the combination restored microbial homeostasis (increasing beneficial bacteria such as *Lactobacillus*) and modulated the glycine–serine–threonine metabolic pathway. Mechanistically, THB + PPD synergistically activated the PI3K/AKT neurotrophic pathway (p-PI3K and p-AKT expression increased by 1.9-fold and 2.5-fold, respectively, vs. model), inhibited the AGE/RAGE pro-inflammatory axis (RAGE expression decreased by 31.8%), and enhanced blood–brain barrier integrity by upregulating tight junction proteins (ZO-1, Occludin). Conclusions: THB combined with PPD exerts synergistic anti-insomnia effects through multi-level regulation of the microbiota–gut–brain axis, neurochemical balance, and key signaling pathways, providing a promising foundation for developing safe natural product-based combination therapies. Full article

Background: Observational fear, a form of empathic response to others’ distress, exhibits marked sex differences. Oxytocin (OT) is a key modulator of social and emotional behaviors, but its role in observational fear—and how this varies by sex and administration route—remains controversial. Methods: We studied behavioral responses in male and female mice during observational fear. We first blocked systemic oxytocin (OT) signaling with a peripheral antagonist. We then tested different routes of OT administration (intranasal, intraperitoneal). Further, we microinjected OT directly into the anterior insular cortex (AIC). Finally, we used a chemogenetics strategy to selectively activate or inhibit OT neurons. Results: Male mice exhibited sustained freezing behavior and elevated corticosterone levels in response to observational fear. In contrast, females more quickly resumed baseline activity levels and showed an increased number of interactions. Systemic blockade of oxytocin (OT) signaling selectively reduced fear expression in males. Strikingly, intranasal OT administration elicited heightened fear-related responses in both sexes, whereas intraperitoneal OT administration induced anxiolytic-like effects. Direct OT microinjection into the anterior insular cortex (AIC) produced sex-divergent reductions in fear responses: decreasing freezing duration in males and reducing avoidance behaviors in females. Chemogenetic activation of OTergic neurons replicated these anxiolytic effects, while inhibition had no effect. Conclusions: OT bidirectionally regulates observational fear in a sex-, route-, and site-specific manner, challenging the simplistic view of OT as universally prosocial. The AIC is a critical node in empathetic fear circuits. These findings underscore the necessity for precision in targeting the OT system for treating stress-related psychiatric disorders. Full article

The efficacy of stigmasterol (STG) has not been previously evaluated in post-traumatic stress disorder (PTSD) models. Mice exposed to single prolonged stress with foot shock (SPS + FS) received oral STG (25 or 50 mg/kg) for 14 days. Serum corticosterone and serotonin levels were measured, anxiety and cognition were assessed, synaptic plasticity-related proteins and genes were quantified, and neuronal nitric oxide synthase (nNOS), nitric oxide (NO) accumulation, nNOS-postsynaptic density protein 95 (PSD95), and nNOS-carboxy-terminal PDZ ligand of nNOS (CAPON) interactions were evaluated. STG significantly reduced serum corticosterone levels and increased serotonin levels altered by SPS+FS exposure. Behavioral analyses revealed attenuation of anxiety-like behavior and cognitive deficits. STG increased hippocampal synaptic plasticity-related proteins and genes and increased the number and maturation of doublecortin⁺ cells. Additionally, STG suppressed the PTSD-induced nNOS overactivation and NO accumulation in the hippocampus and serum, and altered nNOS-PSD95 and nNOS-CAPON associations in the hippocampus. Together, these findings provide integrated in vivo evidence suggesting that STG may influence stress-related neurobiological pathways relevant to PTSD. Full article

Background/Objectives: Homeostatic (nervous, immune and endocrine) systems and their communications network are crucial for health and aging rate. We previously reported behavioral and peritoneal leukocyte function alterations and oxidative-inflammatory stress in young female triple-transgenic (3xTg) mice for Alzheimer’s disease (AD). Here, the deterioration of the homeostatic systems and their interplay was investigated, in an integrated way, at prodromal stages and in both sexes of 3xTg-AD mice. Methods: An integrative analysis of the behavioral profile, peripheral immune splenic and thymic leukocyte functions, splenic oxidative-inflammatory state, and plasmatic corticosterone in both sexes of 3xTg-AD mice at 4 months of age was compared to that of age- and sex-matched NTg counterparts. Results: The prodromal stage of 3xTg-AD, characterized by anxiety-like behaviors and disrupted exploration, was aligned with reduced chemotaxis, natural killer activity, and lymphoproliferation—especially in the spleen. In addition, 3xTg-AD mice exhibited lower anti-inflammatory (IL-10) and higher pro-inflammatory (IL-2, IL-1β, and TNF-α) cytokine concentrations and oxidative stress (higher oxidants and lower antioxidants). Several of these alterations displayed sex-dependent differences (worse in males). However, no differences in corticosterone were found. Conclusions: These findings suggest that neuroimmune and redox-inflammatory dysfunctions, indicative of premature aging, emerge at the prodromal stage of AD, preceding corticosterone changes, unveiling a time lag in the neuroimmunoendocrine alterations in these animals. They may act as early indicators of premature aging in AD pathology and provide potential targets for sex-specific prodromal intervention. Full article

Objectives: This study explored the antidepressant mechanisms of aerobic exercise in CUMS rats by analyzing urinary metabolomics (LC-MS and NMR), with the aim of providing both theoretical and practical support for exercise-based depression interventions. Methods: (1) Thirty-two Sprague-Dawley rats were acclimatized for one week and then randomly assigned to four groups (n = 8 per group): control (C), control + aerobic exercise group (E), CUMS model (D), and CUMS + exercise (DE). Groups D and DE were subjected to nine types of CUMS stimuli. Behavioral indicators were assessed weekly, and the successful establishment of the CUMS model was confirmed at week 3. Following successful modeling, rats in groups E and DE underwent four weeks of aerobic exercise training. Throughout this period, groups D and DE continued to receive CUMS exposure, while groups C and E were maintained under standard control conditions. (2) At the end of week 7, behavioral tests were repeated. Twelve-hour urine samples were collected for metabolomic analysis using liquid chromatography–mass spectrometry (LC-MS) and ¹H-NMR spectroscopy. The following morning, rats were euthanized under anesthesia. Whole blood was collected from the abdominal aorta, and serum was separated for subsequent biochemical assays. Bioinformatics approaches were employed to identify potential targets and signaling pathways associated with the antidepressant effects of aerobic exercise. (3) For statistical analysis, one-way or two-way analysis of variance (ANOVA) was applied to behavioral, physiological, and biochemical data, whereas multivariate statistical analysis was used for metabolomic data. Results: (1) By week 3, body mass, sucrose preference, rearing frequency, and the number of grid crossings were significantly lower in groups D and DE than in groups C and E (p < 0.05 or p < 0.01). These findings confirmed the successful establishment of the depression model. At week 7, all behavioral indicators in group DE showed significant recovery relative to group D (p < 0.05 or p < 0.01). (2) Compared with group C, corticosterone and blood ammonia levels were significantly elevated in group D (p < 0.01). In contrast, these levels were markedly reduced in group DE compared with group D (p < 0.01). (3) LC-MS analysis identified 25 urinary metabolites associated with depression in group D relative to group C. Among these, 21 were significantly downregulated and 4 were upregulated (p < 0.05 or p < 0.01), involving seven metabolic pathways. Following aerobic exercise intervention, six of these depression-related metabolites in group DE showed significant recovery (p < 0.05 or p < 0.01), which were associated with two metabolic pathways. (4) Integrated analysis of LC-MS and ¹H-NMR data revealed glutamine as a common differential metabolite, linked to three metabolic pathways. All metabolic pathways modulated by aerobic exercise were related to amino acid metabolism. (5) Bioinformatics analysis indicated that AKT1, MTOR, IL6, RAF1, and TNF were core targets through which aerobic exercise regulated urinary metabolism in CUMS rats. Conclusions: A four-week regimen of aerobic exercise significantly improved depressive-like behaviors and enhanced anti-fatigue capacity in CUMS rats. This exercise regimen promoted urinary metabolic remodeling, primarily through the modulation of amino acid metabolism. Furthermore, its antidepressant effect is likely mediated through the regulation of core tissue targets—including AKT1, mTOR, IL-6, RAF1, and TNF—thereby influencing key pathways such as PI3K-AKT, MAPK/ERK, and neuroinflammatory signaling. Full article

Objectives: Existing animal models of post-traumatic stress disorder (PTSD) are often methodologically complex and produce variable outcomes. The aim of this study was to develop a modified PTSD model that accurately recapitulates the clinical progression of the disorder, incorporating both behavioral features and objective physiological parameters. Methods: We utilized a modified Single Prolonged Stress with Subsequent Stress (SPS&S) protocol, supplemented by a stress reminder phase (without re-exposure to primary stressors) and an evaluation of stress response extinction. Eighty male Wistar rats were subjected to the stress protocol, followed by comprehensive behavioral, hematological (leukocytes, hemoglobin, and hematocrit), and hormonal (corticosterone; adrenocorticotropic hormone (ACTH)) assessments 4–5 weeks post-stress. Results: The model produced a PTSD-like phenotype in 25% of animals, characterized by persistent alterations in the investigated biomarkers. The PTSD group exhibited sustained behavioral impairments (increased anxiety), hematological changes (neutrophilic leukocytosis), and endocrine dysregulation (decreased corticosterone, ACTH, and epinephrine). Conclusions: This modified SPS&S model demonstrates validity for studying the long-term consequences of stress, with PTSD markers remaining stable throughout the 28-day observation period. Full article