Search Results (908)

Background: Histamine H3 receptor-targeting compounds modulate histaminergic tone and downstream monoaminergic/arousal circuits and have been proposed to exert potential antidepressant-like effects in preclinical models. Methods: We conducted a systematic review and meta-analysis of rodent studies evaluating H3-related interventions on depression-like behavior. We screened 60 records, assessed 12 studies qualitatively (four CORE, eight sensitivity), and included nine studies in random-effects meta-analyses (REML). Primary outcomes were the forced swim test (FST) and tail suspension test (TST); effect sizes were summarized as Hedges’ g (positive values indicate reduced immobility). Results: In the primary ALL analysis, H3-related interventions improved FST outcomes (g = 1.40, 95% CI 0.83–1.97; k = 7) and were also associated with improved TST outcomes, albeit with substantial heterogeneity (g = 2.27, 95% CI 0.80–3.73; k = 5). CORE-only analyses were directionally consistent but less precise (FST: g = 1.11, 95% CI −0.06–2.27; k = 3; TST: g = 2.95, 95% CI 0.87–5.02; k = 2). Sucrose preference was reported in one study and indicated improvement (g = 1.61, 95% CI 0.29–2.92). Conclusions: H3-related interventions show an antidepressant-like signal in rodent FST and TST, with greater heterogeneity for TST, highlighting the need for more standardized and adequately powered preclinical studies. Full article

Autism Spectrum Disorder (ASD) is a lifelong condition marked by challenges in social communication and repetitive behaviors. Current treatments, primarily behavioral therapies, often fail to address the core symptoms. Recent research has explored the potential of psychedelics, such as LSD, psilocybin, and MDMA, as a new therapeutic approach. While these substances primarily modulate the serotonin 5-HT_2A receptor, their therapeutic effects also involve interactions with other serotonergic, dopaminergic, and glutamatergic pathways, collectively promoting neuroplasticity—the brain’s ability to change and adapt. The specific receptors’ activation leads to structural and functional changes in the brain that can enhance social behavior and emotional regulation. Studies show that psychedelics may reduce symptoms of conditions like treatment-resistant depression and PTSD, highlighting their therapeutic potential. For ASD specifically, psychedelics may improve psychological flexibility, reduce distress, and enhance social interaction. While promising, the use of these substances requires careful consideration. Psychedelics can induce intense experiences and altered states of consciousness, necessitating strict monitoring and support during therapy. Ethical guidelines, including informed consent, are crucial, especially for vulnerable populations. In conclusion, psychedelics hold significant promise for treating ASD and other psychiatric disorders by promoting neuroplasticity and modulating complex signaling pathways. Continued research and clinical trials, conducted with strong ethical oversight, are essential to realizing their full therapeutic potential. Full article

This study systematically compared the induction and resuscitation characteristics of the viable but non-culturable (VBNC) state in Klebsiella pneumoniae FY170-1 following sublethal exposure to sodium hypochlorite (NaClO) or glutaraldehyde (GA). Treatment with 30 mg/L NaClO or 60 mg/L GA for 60 min reduced culturability to below the detection limit (<1 CFU/mL). However, CTC staining showed that 50.80% and 63.44% of cells, respectively, retained respiratory activity, while SYTO 9/PI staining indicated that membrane integrity was largely preserved, consistent with induction of the VBNC state. Scanning electron microscopy revealed distinct morphological alterations in the two groups. NaClO-induced VBNC cells showed surface depressions and wrinkling, consistent with oxidative damage, whereas GA-induced cells exhibited filamentous and net-like surface structures, consistent with aldehyde-mediated cross-linking. Among the tested additives, sodium succinate showed the strongest resuscitation-promoting effect under the experimental conditions, with OD600 increasing after approximately 2 h of incubation. Post-resuscitation analysis further revealed marked differences between the two VBNC states. In resuscitated NaClO-induced VBNC cells, ATP partially recovered, but reactive oxygen species remained elevated and catalase activity showed little recovery. In contrast, resuscitated GA-induced VBNC cells exhibited lower ATP recovery but more rapid normalization of ROS and better recovery of oxidative stress-related parameters. Total protein analysis and SDS-PAGE further supported distinct patterns of protein-level alteration between the two treatments. Overall, these findings suggest that NaClO and GA induce phenotypically distinct VBNC states in K. pneumoniae, with different recovery behaviors and stress response profiles. Sodium succinate was identified as the most effective recovery-promoting additive under the tested conditions. These results highlight the risk of underestimating bacterial survival when culturability is used as the sole indicator of disinfection efficacy and support the need for more comprehensive viability assessment. Full article

Background: Developing physical literacy in children with developmental disabilities (DDs) is essential to fostering their participation in physical activity. According to the Canadian Framework, physical literacy encompasses multiple interrelated components (behavioral, physical, affective, and cognitive). Such engagement provides numerous benefits, including reduced symptoms of anxiety and depression, as well as improved functional and cognitive health. However, children with DD appear to be less active than those without such conditions. Since individuals who are active during childhood and adolescence are more likely to remain active during adulthood, it becomes crucial to better understand how to support the physical literacy development of children with DD, hence enhancing their participation in physical activity. In addition, children with DD remain underrepresented in the literature, particularly with regard to their opportunities to develop their physical literacy and their varied needs, such as limited physical activity options. Objective: The aim of this scoping review was to identify and analyze the existing literature on the development of physical literacy and physical activity participation in young children (0–6 years) with DD. Methods: Four databases were searched (PsycInfo: n = 722; MEDLINE: n = 997; ERIC: n = 514; CINAHL: n = 771), and 25 articles were retained. Characteristics of these studies were analyzed quantitatively, while their scope was analyzed according to physical literacy components. Results: Most studies (80%) used a quantitative method, and nearly half (44%) concerned young children with autism spectrum disorder. A little more than half of the studies (52%) focused on early intervention programs. In regard to the scope of the studies, none addressed the cognitive component of physical literacy, indicating a lack in the current literature, and more than half provided information on how to support the affective component. Moreover, information regarding parents’ involvement in physical activity of children with DD emerged from six studies analyzed. Conclusions: The results yield interesting insights on how to support the physical literacy development of children with DD and the factors likely to influence their physical activity participation. Early intervention programs promoting physical literacy could be promising avenues to support lifelong physical activity habits for these children. Full article

We examined how sociodemographic, parental, and temporal factors are associated with parent-reported reasons for seeking consultation in a child and adolescent psychotherapeutic clinic. Data were derived from a large retrospective sample of more than 3000 cases collected between 2011 and 2023. Multivariable binary logistic regression analyses assessed the independent effects of age, gender, living arrangements, migration background, parental education, parental age at childbirth, parental separation or bereavement, and pandemic-related periods. School-aged children and adolescents were more likely than younger children to present with learning difficulties, depression, anxiety, mobbing and media addiction. Female patients showed lower odds of consultations related to learning difficulties, aggression, behavioral addiction, attention deficit/hyperactivity, but higher odds of depression, psychosomatic symptoms, anxiety, eating disorders and sleeping disorders. Parental separation increased the likelihood of consultations related to problematic social behavior within the family, delinquency and trauma and grief. Consultations for attention deficit/hyperactivity concerns were more frequent in the post-pandemic period compared to pre-pandemic. The findings highlight that sociodemographic, familial, and temporal factors are systematically associated with distinct patterns of parent-reported help-seeking patterns in child and adolescent psychotherapeutic care. Full article

Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg/kg/day) and 17 β-estradiol (EST, 0.5 mg/kg/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) α, ERβ, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ERα and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ERβ antagonist, PHTPP (200 μg/kg/day), was used to clarify the role of ERβ. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg/mL), EMO-treated (2.57 pg/mL) and EST-treated OVX rats (2.64 pg/mL), were higher than that of OVX rats (1.03 pg/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ERβ in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ERβ in colon and cerebral ERα level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ERβ, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Erβ-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals. Full article

Objective: ZhiZhu Kuanzhong (ZZKZ) capsule, a Chinese herbal extract, is extensively employed for the clinical management of functional dyspepsia (FD) in China. This study aimed to elucidate the therapeutic efficacy and underlying mechanisms of ZZKZ on the co-morbidity of anxiety and depression of FD. Methods: The FD model was established in Sprague–Dawley rats via neonatal gastric irritation with 0.1% iodoacetamide. Subsequently, FD rats were gavaged with ZZKZ or fluoxetine. Depression-like behaviors were evaluated using the sucrose preference test (SPT) and forced swimming test (FST), while anxiety-like behaviors were assessed via light-dark box (LDB) and open field tests (OFTs). Network pharmacology and molecular docking were conducted to explore the mechanisms of ZZKZ’s action. Hippocampal levels of monoamine neurotransmitters and monoaminergic system components were evaluated by HPLC and RT-qPCR, respectively. Serum concentrations of HPA axis hormones were determined by ELISA. Results: ZZKZ administration reversed the deficits in body weight gain and food intake in FD rats. Behaviorally, ZZKZ increased sucrose consumption in SPT and prolonged swimming duration in FST, and it increased duration and entries into the central zone in OFT. According to the prediction of network pharmacology, ZZKZ treatment elevated hippocampal levels of 5-HT/NE/DA, increased expression of TPH2/TH, and decreased expression of MAO_A/SERT in FD rats. Molecular docking further confirmed high-affinity binding between core ingredients of ZZKZ and TPH2/TH/MAO_A/SERT. Moreover, ZZKZ administration attenuated the stress-induced elevation of serum CRH/ACTH/CORT. Conclusions: ZZKZ effectively ameliorates the disordered gut–brain interaction and mitigates anxiety-like and depression-like behaviors, which might be modulated by the hippocampal monoaminergic system and hypothalamic–pituitary–adrenal axis response. Full article

Chronic social isolation (CSIS) is a form of psychosocial stressor strongly associated with the development of depression. Preclinical studies demonstrated that CSIS induces behavioral phenotypes resembling human depression, including anhedonia, behavioral despair and anxiety. This review summarizes proteomic-driven discoveries characterizing hippocampal non-synaptic mitochondria (NSM) and synaptosomal fractions containing synaptic mitochondria from adult male rats exposed to six weeks of CSIS, an animal model of depression, compared to controls. The compartment-specific proteomic alterations reveal mechanisms underlying mitochondrial dysregulation, providing molecular insights into the depression-like phenotype. Hippocampal NSM exhibit changes in energy metabolism-related proteins, including components of the tricarboxylic acid cycle and oxidative phosphorylation, as well as mitochondrial transport proteins and alterations in chaperones, structural and translational proteins, and monoamine oxidase, further elucidating how these proteomic changes contribute to mitochondrial dysregulation. In contrast, synaptosomal proteomics reveal predominantly increased protein abundance associated with energy metabolism, signaling, cytoskeletal organization, protein quality control, and vesicle trafficking, suggesting compensatory adaptations. Together, these findings highlight compartment-specific mitochondrial proteomic changes that may underlie depression-like behaviors and represent potential targets for therapeutic intervention. 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

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic–pituitary–adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan–kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors. Full article

Sleep disturbances are early hallmarks of Alzheimer’s disease (AD) and other dementias, yet the molecular mechanisms remain poorly understood. We previously showed that dipeptidyl aminopeptidase-like protein 6-knockout (DPP6-KO) mice exhibit accelerated neurodegeneration with synaptic loss, neuronal death, and circadian dysfunction resembling AD pathology. Here, we investigate whether DPP6 deficiency directly causes sleep dysregulation and assess age-dependent effects using wireless EEG/EMG telemetry, behavioral monitoring, and body temperature recordings. We found striking age-dependent sleep phenotypes in DPP6-KO mice. Adult (3-month) DPP6-KO mice showed hyperactivity-driven REM sleep increases, while aged (12-month) DPP6-KO mice developed insomnia with fragmented sleep architecture. Critically, aged DPP6-KO mice exhibited decreased REM latency, a biomarker of depression, which we confirmed by behavioral assays. Conversely, DPP6 overexpression in aged wild-type mice increased NREM duration and reduced sleep fragmentation, demonstrating a protective effect. Throughout aging, DPP6-KO mice showed dysregulated locomotor activity and body temperature rhythms, suggesting broader disruption of circadian and metabolic homeostasis. These findings establish DPP6 as a critical regulator of sleep architecture whose loss recapitulates key sleep disturbances observed in AD/dementia. The progressive nature of sleep dysfunction in DPP6-KO mice, from REM abnormalities to insomnia, parallels human disease progression and positions DPP6 as a potential therapeutic target for sleep-related symptoms in neurodegenerative disorders. Full article

The role of the endocannabinoid system (ECS) in the development of depression and anxiety is being actively studied, with evidence suggesting that elevation of ECS signaling can have anxiolytic and antidepressant properties. The current study explored the therapeutic potential of Oleoyl Serine (OS), an endocannabinoid-like lipid, and HU-910, a synthetic selective Cannabinoid type 2 (CB2) receptors agonist, in depression and anxiety, using both sexes of the depressive-like genetic model: Wistar Kyoto (WKY) rats. The aim was to investigate behavioral and molecular mechanisms associated with acute and sub-chronic intraperitoneal administration of these compounds. We showed that, in females, acutely administered OS yielded antidepressant-like and anxiolytic-like effects in the Forced Swim Test (FST) and Open Field Test (OFT), respectively. In males, OS yielded acute and sub-chronic anxiolytic-like effects. HU-910 yielded an acute anxiolytic-like effect in females and an acute antidepressant-like effect in males. Sub-chronic administration of imipramine (IMI), used as a positive control, yielded an antidepressant-like effect in both sexes but an anxiogenic-like effect in females. Sub-chronic administration of all the treatments increased hippocampal Cannabinoid Receptor 1 (CNR1) mRNA expression (but not Fatty Acid Amide Hydrolase (FAAH)) in males. Exploratory in silico absorption, distribution, metabolism, and excretion (ADME) profiling suggests that sex-dependent pharmacokinetic variability may partly underlie the observed behavioral differences, in addition to possible pharmacodynamic factors. Our study provides a lead towards unraveling the putative sex differences in response to both conventional antidepressants (e.g., IMI) and emerging pharmacological agents (e.g., OS, HU-910). Further, our study helps advance the field of neuropharmacology by elucidating the anxiolytic-like and antidepressant-like effects of OS and HU-910. Full article

Fibromyalgia is a chronic nociplastic pain condition frequently accompanied by affective disturbances, particularly depression, for which effective treatments remain limited. Increasing evidence implicates central oxidative stress, maladaptive synaptic plasticity, and neuroinflammatory alterations in its pathophysiology. This study investigated the therapeutic effects of molecular hydrogen (H₂) in a reserpine-induced murine model of fibromyalgia, with emphasis on sex-dependent and region-specific mechanisms. Male and female C57BL/6 mice received repeated reserpine injections to induce fibromyalgia-like symptoms. Mechanical allodynia, thermal hyperalgesia, cold allodynia, and depressive-like behaviors were assessed, followed by molecular analyses in the spinal cord and amygdala. Reserpine induced persistent nociceptive hypersensitivity and depressive-like behaviors in both sexes, with earlier cold allodynia in females. Hydrogen-rich water (HRW) progressively reversed mechanical and thermal hypersensitivity and rapidly abolished cold allodynia, showing greater efficacy in females. HRW also normalized depressive-like behaviors in both sexes. At the molecular level, HRW reduced spinal oxidative stress and ERK-dependent plasticity without altering spinal NLRP3 expression, whereas it fully reversed NLRP3 upregulation and HO-1 downregulation in the amygdala. HRW additionally engaged sex-dependent antioxidant pathways in the spinal cord. These findings indicate that H₂ alleviates sensory and affective alterations through region- and sex-dependent central mechanisms, supporting HRW as a promising therapeutic strategy for nociplastic pain and its affective comorbidities. Full article

Reward motivation adaptation is defined as the extent to which the willingness to exert effort varies as a function of incentive salience, encompassing both motivational (‘wanting’) and hedonic (‘liking’) components. Although reduced reward motivation has been reported in subclinical depression and anhedonia, it remains unclear whether impaired adaptation is a general feature of subclinical depression or is more evident when depressive symptoms co-occur with anhedonia. We addressed this question in two behavioral studies using a task that systematically varied effort–reward ratios. Study 1 contrasted three screening-based groups: individuals with elevated social anhedonia, individuals with subclinical depression without high social anhedonia, and controls with low levels of both, and found no clear group differences in reward motivation adaptation across effort–reward conditions. Study 2 focused on female participants with subclinical depression who also showed higher levels of anhedonia, compared with non-depressed controls. In this sample, the subclinical depression group showed lower overall reward motivation and indications of reduced ‘liking’ adaptation. In conclusion, these findings suggest that deficits in reward motivation adaptation were not clearly observable when subclinical depression or social anhedonia were considered in isolation, but may emerge when depressive status and broader measures of anhedonia co-occur, though this pattern requires confirmation in larger and more diverse samples. Full article

Major depressive disorder (MDD) is a highly prevalent psychiatric illness for which rapid-acting antidepressants such as ketamine provide only transient benefit. Because κ-opioid receptor (KOR) signaling contributes to stress-related dysphoria and impaired neuroplasticity, we examined whether KOR antagonism could prolong ketamine’s antidepressant-like effects in a mouse model of adolescent chronic unpredictable stress (CUS). Male C57BL/6J mice (n = 10 per group for behavioral analyses) were exposed to CUS during adolescence and developed persistent depression-like behavior in adulthood. Mice with depressive-like behavior received a single injection of ketamine, the selective KOR antagonist norbinaltorphimine (nBNI), or their combination. Behavioral testing showed that all treatments reduced immobility in the tail suspension test (TST) 24 h post-administration; however, only the combined ketamine/nBNI treatment maintained antidepressant-like effects one week post-treatment. Molecular analyses (n = 4–8 per group) were conducted at this single time point, one week post-treatment, to characterize region-specific signaling states in the prefrontal cortex, hippocampus, and striatum, focusing on ERK, AKT, JNK, mTOR, and BDNF pathways. These molecular findings represent correlates of sustained behavioral effects rather than evidence of causal mechanisms. Together, the data indicate that concurrent KOR antagonism is associated with prolonged antidepressant response to ketamine in stress-exposed male mice and with distinct region-dependent signaling profiles at one week post-treatment. Further studies are needed to establish mechanistic causality and confirm the possible applicability of these findings. Full article