Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 14, 2025

Schizophrenia (SZ) is a deleterious brain disorder characterised by its heterogeneity and complex symptomatology consisting of positive, negative cognitive deficits. Current antipsychotic drugs ameliorate the positive symptomatology, but are inefficient in treating The neurodevelopmental glutamate hypothesis SZ has opened new avenues development targeting glutamatergic system. One these therapies involves allosteric modulators (PAMs) metabotropic receptors, mainly types 2/3 (mGluR2/3). mGluR2/3 PAMs selective for receptor, present high tolerability can modulate activity receptor long periods. There not much research clinical trials regarding PAMs. However, several lines evidence from animal models have indicated efficiency In this review, focusing on vivo studies, we will specifically discuss utilization various methods employed to assess behaviour before summarising obtained date field By doing so, aim deepen our understanding underlying mechanisms potential SZ. Overall, demonstrated attenuating SZ-like behavioural molecular deficits could be useful early management or treat specific subsets patients.

Язык: Английский

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Progress in the study of oxidative stress damage in patients with schizophrenia: challenges and opportunities

Frontiers in Psychiatry, Год журнала: 2025, Номер 16

Опубликована: Фев. 21, 2025

Schizophrenia is a serious psychiatric disorder of multifactorial triggers, with lifetime prevalence about 1% in all countries the world, slightly higher males than females, and peak incidence between ages 15-35 years old, poor prognosis for most patients, which imposes heavy burden on society family. Early intervention important regression patients. More more studies have found that imbalance oxidation antioxidant, persistent damage to brain by oxidative stress play an role occurrence development schizophrenia. Antioxidants, as additive therapy, improving symptoms well preventing relapse patients This paper intends address pathogenesis injury schizophrenia, significance treatment

Язык: Английский

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KEAP1‐NRF2/HO‐1 Pathway Promotes Ferroptosis and Neuronal Injury in Schizophrenia

Brain and Behavior, Год журнала: 2025, Номер 15(3)

Опубликована: Фев. 28, 2025

ABSTRACT Background This study investigates the role of KEAP1‐NRF2/HO‐1 signaling pathway in inducing ferroptosis and contributing to neuronal damage schizophrenia. Methods We retrieved schizophrenia‐related data ferroptosis‐related genes from RNA microarray dataset GSE27383 FerrDB database, respectively. Bioinformatics identified KEAP1 as a downregulated gene, which was validated using qRT‐PCR Western blot. assessed intracellular Fe 2 ⁺ content, MDA levels, GSH, GPX4 prefrontal cortex peripheral blood mononuclear cells (PBMCs) patients with Cortical interneurons (cINs) were generated human‐induced pluripotent stem (hiPSCs) schizophrenia used explore alterations during neurodevelopment. In addition, overexpression induced cINs via transfection pcDNA KEAP1. The Fe⁺ oxidative stress indicators, lipid peroxidation, inflammatory cytokines measured after transfection. To investigate molecular mechanisms, KI696—a high‐affinity probe that disrupts KEAP1–NRF2 interaction—was applied, changes stress, peroxidation (C11‐BODIPY staining), iron metabolism, pathways evaluated. Results Patients exhibited underexpression KEAP1, key regulator ferroptosis, along elevated levels increased concentrations, indicating enhanced stress. Reduced activity GSH also observed, suggesting an susceptibility ferroptosis. further this, derived hiPSCs studied. These showed decreased expression. Overexpression led reduction concentrations damage, highlighting KEAP1's regulatory treatment KI696 significant related antioxidant defenses, inflammation. Conclusion Our findings indicate contributes injury

Язык: Английский

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Investigating the Effect of N-Acetyl Cysteine on Positive, Negative, and Cognitive Symptoms of Patients with Schizophrenia: A Clinical Trial

Iranian Journal of Psychiatry and Behavioral Sciences, Год журнала: 2025, Номер 19(1)

Опубликована: Фев. 9, 2025

Background: Recent studies have identified oxidative stress as a potential neurobiological contributor to the development of schizophrenia. N-acetylcysteine (NAC) is recognized for its potent antioxidant and neuroprotective properties. Objectives: This study aimed evaluate efficacy NAC in reducing treatment Methods: randomized, double-blind, placebo-controlled, parallel-group involved 35 patients with Patients case group received 600 mg once daily addition their routine treatment, while control continued placebo instead NAC. Assessments were conducted using Scale Assessment Positive Symptoms (SAPS), Negative (SANS), neuropsychiatry unit cognitive assessment tool (NUCOG) at baseline, 1 2 months post-treatment. Results: resulted significant improvement SAPS NUCOG indices, well an increase peripheral glutathione (GSH) levels (P < 0.05). Continued use second month positively affected particularly Visuo-constructional variable. No impact on SANS was observed. The limited side effects during period suggest it safe practical option. Conclusions: add-on therapy significantly improved positive symptoms functions schizophrenia but did not affect negative symptoms.

Язык: Английский

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Revealing the Oxidative Stress-Related Molecular Characteristics and Potential Therapeutic Targets of Schizophrenia through Integrated Gene Expression Data Analysis

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Язык: Английский

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Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated Implications for Health and Disease

Metabolites, Год журнала: 2025, Номер 15(3), С. 210 - 210

Опубликована: Март 20, 2025

Tryptophan is an essential amino acid critical for human health. It plays a pivotal role in numerous physiological and biochemical processes through its metabolism. The kynurenine (KYN) pathway serves as the principal metabolic route tryptophan, producing bioactive metabolites, including KYN, quinolinic acid, 3-hydroxykynurenine. Numerous studies are actively investigating relationship between tryptophan metabolism functions. These highlighting interactions among metabolites that may exert synergistic or antagonistic effects, such neuroprotective neurotoxic, pro-oxidative antioxidant activities. Minor disruptions homeostasis of these can result immune dysregulation, contributing to spectrum diseases. diseases include neurological disorders, mental illnesses, cardiovascular conditions, autoimmune diseases, chronic kidney disease. Therefore, understanding roles KYN elucidating contribution health regulation. present review emphasizes their mechanisms disease development, aiming establish theoretical basis leveraging dietary nutrients enhance

Язык: Английский

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Connecting Neurobiological Features with Interregional Dysconnectivity in Social-Cognitive Impairments of Schizophrenia

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7680 - 7680

Опубликована: Апрель 22, 2023

Schizophrenia (SZ) is a devastating psychiatric disorder affecting about 1% of the world’s population. Social-cognitive impairments in SZ prevent positive social interactions and lead to progressive withdrawal. The neurobiological underpinnings social-cognitive symptoms remain poorly understood, which hinders development novel treatments. At whole-brain level, an abnormal activation brain regions interregional dysconnectivity within networks have been identified as major contributors these symptoms. cellular subcellular levels, interplay between oxidative stress, neuroinflammation N-methyl-D-aspartate receptor hypofunction thought underly pathology. However, it not clear how molecular processes are linked with genesis Here, we aim bridge gap macroscale (connectivity analyses) microscale (molecular mechanistic) knowledge by proposing impaired myelination disinhibition local microcircuits possible causative biological pathways leading activity brain. Furthermore, recommend electroencephalography promising translational technique that can foster pre-clinical drug discuss attractive targets for treatment SZ.

Язык: Английский

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Associations between Toxoplasma gondii seropositivity and psychopathological manifestations in schizophrenic patients: A single-center study from Ecuador

PLoS ONE, Год журнала: 2024, Номер 19(2), С. e0297523 - e0297523

Опубликована: Фев. 23, 2024

Background Schizophrenia, a complex neuropsychiatric disorder, is believed to be influenced by various factors including environmental exposures. A potential factor the infection obligate intracellular parasitic protozoan, Toxoplasma gondii which affects neurotransmitter levels, could potentially exacerbate, trigger symptoms of schizophrenia or make them worst. Objective To investigate association between seropositivity and psychopathological presentation in persons with Ecuador. Methods This study was conducted at Neuroscience Institute Guayaquil, Among 368 inpatients, 104 were selected based on specific inclusion exclusion criteria. Descriptive statistics captured patient characteristics mental health outcomes. Logistic regression models estimated effect toxoplasmosis outcomes, controlling for demographic health-related variables. Results 86.5% participants seropositive toxoplasmosis. Toxoplasma-seropositive schizophrenic patients had lower risk depression but significantly higher disorientation. The most prevalent outcomes Language Impairments (70.2%) Bizarre Behavior (76.0%). Conclusion Our findings suggest that may have effects functions patients, particularly reducing increasing Further studies are required clarify these associations underlying mechanisms.

Язык: Английский

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Bilirubin and Redox Stress in Age-Related Brain Diseases

Antioxidants, Год журнала: 2023, Номер 12(8), С. 1525 - 1525

Опубликована: Июль 29, 2023

Cellular redox status has a crucial role in brain physiology, as well pathologic conditions. Physiologic senescence, by dysregulating cellular homeostasis and decreasing antioxidant defenses, enhances the central nervous system’s susceptibility to diseases. The reduction of free radical accumulation through lifestyle changes, supplementation antioxidants prophylactic therapeutic approach increase health, are strongly suggested. Bilirubin is powerful endogenous antioxidant, with more recognized roles biomarker disease resistance, predictor all-cause mortality, molecule that may promote health adults. alteration expression activity enzymes involved bilirubin production, an altered blood level, often reported neurologic conditions neurodegenerative diseases (together denoted NCDs) aging. These changes predict or contribute both positively negatively Understanding onset progression NCDs will be functional consider benefits vs. drawbacks hypothesize best strategies for its manipulation purposes.

Язык: Английский

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Pilot study indicates that a gluten-free diet lowers oxidative stress for gluten-sensitive persons with schizophrenia

Schizophrenia Research, Год журнала: 2024, Номер 269, С. 71 - 78

Опубликована: Май 14, 2024

Язык: Английский

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