Journal of Neurochemistry最新文献

{"title":"CysLT1 Receptor Activation Decreases Na+/K+-ATPase Activity via PKC-Mediated Mechanisms in Hippocampal Slices","authors":"Leonardo Magno Rambo,&nbsp;Quéli Fernandes Lenz,&nbsp;Fernanda Rossatto Temp Fava,&nbsp;Laura Hautrive Milanesi,&nbsp;Joseane Righes Marafiga,&nbsp;Ana Cláudia Jesse,&nbsp;Carlos Fernando Mello","doi":"10.1111/jnc.70257","DOIUrl":"10.1111/jnc.70257","url":null,"abstract":"<p>Leukotrienes (LTs) are potent bioactive lipids derived from the 5-lipoxygenase (5-LOX)-mediated metabolism of arachidonic acid (AA). Growing evidence suggests that leukotrienes contribute to the pathophysiology of several inflammatory disorders of the central nervous system. However, the molecular mechanisms by which cysteinyl leukotrienes (CysLTs) facilitate excitatory activity remain poorly understood. Sodium/potassium-ATPase (Na⁺/K⁺-ATPase) is a plasma membrane protein essential for maintaining ionic gradients and regulating membrane excitability, and its reduced activity has been implicated in increased excitability within the central nervous system. In the present study, we demonstrate that LTD₄ decreases Na⁺/K⁺-ATPase activity (α₁ and α_2/3 subunits) in hippocampal slices from adult male Swiss mice. Furthermore, the intracerebroventricular (i.c.v.) administration of LTD₄ reduced Na⁺/K⁺-ATPase activity ex vivo, reinforcing the pathophysiological relevance of our in vitro findings. The LTD₄-induced decrease in Na⁺/K⁺-ATPase activity was prevented by both the CysLT₁ receptor (CysLT₁R) inverse agonist montelukast and an anti-CysLT₁R antibody, as well as by the PKC inhibitor GF109203X. Moreover, LTD₄ increased PKC phosphorylation and enhanced Ser-16 phosphorylation of Na⁺/K⁺-ATPase. These effects were also prevented by PKC inhibition. In summary, our findings demonstrate that CysLT₁R activation inhibits hippocampal Na⁺/K⁺-ATPase activity in mice through a PKC-dependent mechanism, providing a potential molecular basis for LTD₄ involvement in the pathophysiology of various neurological disorders.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Molecular Docking to Rat Models: Butyrate From a High-Fiber Diet Inhibits HDAC1 and NLRP3 Inflammasome to Alleviate Oxidative Stress and Inflammation After Spinal Cord Injury","authors":"Kong Ganggang,&nbsp;Gu Cheng,&nbsp;Li Gang,&nbsp;Zhang Wenwu,&nbsp;Zhang Di,&nbsp;Li Yan,&nbsp;Xie Baoshu,&nbsp;Wang Yiqin","doi":"10.1111/jnc.70250","DOIUrl":"10.1111/jnc.70250","url":null,"abstract":"<div>\u0000 \u0000 <p>Spinal cord injury (SCI) induces complex inflammatory and oxidative stress responses that exacerbate secondary damage and impair functional recovery. This study investigated the role of butyrate—a microbiota-derived short-chain fatty acid (SCFA)—in ameliorating SCI using a combination of <i>in silico</i>, in vitro, and in vivo approaches. We first performed gut microbiota 16S rRNA sequencing and targeted metabolomics to assess microbial dysbiosis and serum SCFA levels in rats post-SCI. A marked reduction in butyrate-producing Firmicutes and serum butyrate concentrations was observed after injury. Molecular docking predicted a direct interaction between butyrate and HDAC1, which was confirmed by a ~40% reduction in HDAC1 expression in spinal cord tissue, as demonstrated by Western blot and immunofluorescence. In microglial cultures, butyrate significantly inhibited LPS + ATP-induced NLRP3 inflammasome activation by approximately 38%. For the in vivo component, a cervical hemi-contusion SCI model at the C5 level was established in rats. To restore butyrate levels, animals were either fed a high-fiber diet (HFD) or received intrathecal butyrate administration. Behavioral assessment revealed a 1.5-fold improvement in Forelimb Locomotor Scale scores at 1 month post-injury, and motor-evoked potential recordings showed nearly a 1.8-fold enhancement, indicating significantly improved locomotor and electrophysiological recovery in HFD-treated rats compared to controls. Furthermore, HFD treatment resulted in reduced oxidative stress (as evidenced by lower MDA and DHE staining), decreased inflammation, while butyrate administration promoted M2-type macrophage/microglia polarization. These findings reveal that butyrate mitigates oxidative stress and inflammation by targeting HDAC1 and the NLRP3 inflammasome. Importantly, HFD-driven restoration of microbial butyrate production represents a promising and translationally relevant non-invasive therapeutic strategy to enhance SCI recovery via the gut-spinal cord axis.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Amino Acid and Carnitine Metabolite Profile for the Early Detection and Differential Diagnosis of Alzheimer's Disease","authors":"Xiaoqi Chu,&nbsp;Yunchu Guo,&nbsp;Yu Fu,&nbsp;Hongling Ren,&nbsp;Hairong Wang,&nbsp;Chunhao Shen,&nbsp;Ruiyao Song,&nbsp;Qingyan Zeng,&nbsp;Fatima Elzahra E. M. Ibrahim,&nbsp;Yuhao Li,&nbsp;Yusong Ge","doi":"10.1111/jnc.70234","DOIUrl":"10.1111/jnc.70234","url":null,"abstract":"<div>\u0000 \u0000 <p>As the most common type of dementia, Alzheimer's disease (AD) often presents challenges in terms of early identification. In particular, there is a notable lack of reliable and accessible biomarkers. To measure the levels of amino acids and carnitine metabolites in the peripheral blood of AD patients to identify cognitive impairment-associated metabolites, two cohorts were recruited in this cross-sectional study from September 2018 to October 2023. Serum amino acid and carnitine levels were measured using liquid chromatography–mass spectrometry. The test cohort (normal cognition (NC), <i>n</i> = 70; amnesic mild cognitive impairment (aMCI), <i>n</i> = 41; dementia, <i>n</i> = 92) was used to analyze differences in serum amino acid and carnitine levels and to create a metabolite profile. The diagnostic performance of the metabolite profile was first assessed within the test cohort through receiver operating characteristic (ROC) curve analysis and machine learning approaches. Subsequent cognitive impairment subgroup analysis further confirmed its diagnostic efficacy. Finally, the validation cohort (NC, <i>n</i> = 10; aMCI, <i>n</i> = 10; dementia; <i>n</i> = 10; FDPV (FTD, DLB, PDD and VaD), <i>n</i> = 30) was used to determine the diagnostic and differential diagnostic capabilities of the metabolite profile. In the test cohort, serum levels of a total of 36 amino acids and carnitine metabolites were dysregulated. A profile of seven key metabolites successfully identified patients with NC, aMCI, and dementia. Cognitive subgroup (based on the Montreal Cognitive Assessment) analysis revealed that the profile was suitable for screening for mild, moderate, and severe cognitive impairment. The validation cohort further demonstrated the successful application of the metabolic profile for the discrimination of NC, aMCI, and dementia, as well as for the differential diagnosis of dementia and FDPV. In conclusion, extensive alterations in amino acid and carnitine metabolism levels were found in the peripheral blood of dementia patients, and a profile of seven amino acids and carnitine could be used as potential indicators for aMCI and dementia.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurons in Need: Glucose, but Not Lactate, Is Required to Support Energy-Demanding Synaptic Transmission","authors":"Jens V. Andersen,&nbsp;Mary C. McKenna","doi":"10.1111/jnc.70255","DOIUrl":"10.1111/jnc.70255","url":null,"abstract":"<p>The brain derives its energy from a combination of several metabolic substrates. The principal energy substrate of the brain is glucose, but the metabolic role of cerebral lactate has been debated for decades. In particular, the hypothesis that astrocyte-derived lactate is needed to fuel neuronal metabolism during activation remains a heated topic. This Editorial highlights a study in the current issue of Journal of Neurochemistry exploring the metabolic relationship between glucose and lactate metabolism in sustaining neuronal network signaling. The study by Söder et al. demonstrates that neurons are only able to sustain energy-demanding synchronized synaptic transmission when glucose is freely available. Blocking lactate transport had no effect on neuronal signaling when glucose was present, highlighting that any potential transfer of lactate is not required during high neuronal workload. In fact, when lactate was supplied as the primary fuel, neurons were unable to sustain synchronized signaling. Using a lactate biosensor, the authors further show that neurons produce and release lactate, both during resting and stimulated conditions. As synchronized synaptic transmission underlies higher brain function, this paper underscores the absolute necessity of neuronal glucose metabolism to maintain brain function.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate Transport via Glial MCT1 and Neuronal MCT2 Is Not Required for Synchronized Synaptic Transmission in Hippocampal Slices Supplied With Glucose","authors":"Lennart Söder,&nbsp;Felipe Baeza-Lehnert,&nbsp;Babak Khodaie,&nbsp;Amr Elgez,&nbsp;Lena Noack,&nbsp;Andrea Lewen,&nbsp;Stefan Hallermann,&nbsp;Gernot Poschet,&nbsp;Karin Borges,&nbsp;Oliver Kann","doi":"10.1111/jnc.70251","DOIUrl":"10.1111/jnc.70251","url":null,"abstract":"<p>The metabolite lactate (L-lactate) has been hypothesized to represent an important energy source during brain activation. The contribution of lactate in fueling synchronized synaptic transmission during fast neural network oscillations underlying complex cortex function such as visual perception, memory formation, and motor activity is less clear, however. We explored the role of cellular lactate production and lactate transport (uptake and release) via the monocarboxylate transporters 1 and 2 (glial MCT1 and neuronal MCT2) during persistent gamma oscillations (frequency at around 40 Hz) and recurrent rhythmic events called sharp wave-ripples (with “ripples” at around 250 Hz) in cultured rat and acute mouse hippocampal slices (ex vivo) that received energy substrate supply with glucose (D-glucose) only. In addition, we assessed neuronal lactate dynamics during spontaneous activity (“resting state”) and during electrical stimulation (10 Hz) in mouse primary neuron-astrocyte cultures (in vitro) receiving glucose only. We combined electrophysiology (local field potential recordings), tissue lactate analysis [ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)], and live-cell fluorescence imaging [Förster resonance energy transfer (FRET) sensor Laconic]. We report that (1) lactate is produced during gamma oscillations when glucose is supplied and oxygen availability is unlimited (high oxygenation) for mitochondrial respiration. (2) The properties of gamma oscillations remain regular in the presence of the MCT1/2 blocker AR-C155858. (3) By contrast, MCT1/2 blockade fully suppresses gamma oscillations when mainly lactate is supplied. (4) The properties of sharp wave-ripples remain regular during MCT1/2 inhibition. (5) Lactate is produced in primary hippocampal neurons during spontaneous activity and electric stimulus-induced excitation, and it accumulates in the neuronal cytosol during MCT1/2 inhibition. In conclusion, lactate is produced in cortical tissue, including neurons fueled by glucose only. Moreover, lactate transport and lactate exchange (“shuttling”) via glial MCT1 and neuronal MCT2 are not required to sustain synchronized synaptic transmission during fast neural network oscillations.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trifluoperazine, an Antipsychotic Drug, Inhibits Viability of Cells Derived From SEGA and Cortical Tubers Cultured In Vitro","authors":"Malgorzata Urbanska,&nbsp;Krzysztof Sadowski,&nbsp;Aleksandra Stawikowska,&nbsp;Ewa Liszewska,&nbsp;Magdalena Mlostek,&nbsp;Wieslawa Grajkowska,&nbsp;Katarzyna Kotulska","doi":"10.1111/jnc.70247","DOIUrl":"10.1111/jnc.70247","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to identify compounds that inhibit the growth of cells with a hyperactive mTOR pathway, offering potential treatment options for Tuberous Sclerosis Complex (TSC). We obtained cells from subependymal giant cell astrocytoma (SEGA) and cortical tuber (CTuber) tissues of TSC patients to establish SEGA and CTuber cell strains. Focusing on these patient-derived cell strains, we screened eight compounds from various drug classes for their effects on cell viability in vitro. Five of these compounds demonstrated significant reductions in cell viability and effectively disrupted mTORC1 signaling and autophagy. Trifluoperazine, which exhibited no adverse effects on normal astrocytes, was selected for further study. Combination studies with rapamycin were conducted to evaluate their joint effects on cell viability and autophagy abnormalities, especially in SEGA-derived cells from rapamycin-resistant patients. Notably, trifluoperazine showed promising properties by maintaining its efficacy in combination with rapamycin and effectively reducing cell viability, even in rapamycin-resistant SEGA-derived cells. Trifluoperazine appears promising as a treatment for TSC. However, further research is crucial to confirm its therapeutic benefits and safety profile in TSC patients, representing a significant direction for future TSC management studies.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-Derived Neurotrophic Factor (BDNF) and Sex Differences in Metabolic Regulation","authors":"Ariane M. Zanesco,&nbsp;Licio A. Velloso","doi":"10.1111/jnc.70245","DOIUrl":"10.1111/jnc.70245","url":null,"abstract":"<p>For decades, most experimental studies were conducted using male rodents as models, and the results obtained in several distinct fields of medical and biological research were regarded as valid for both males and females. However, as evidence progressively challenged this concept by unveiling phenotypes that are regulated according to a pattern of sexual dimorphism, many studies were undertaken to identify the mechanisms driving sex-specific characteristics. In this context, hypothalamic brain-derived neurotrophic factor emerged as an important player regulating metabolism according to a sexual dimorphic pattern. Here, we performed a narrative review that puts together the main pieces of evidence showing how brain-derived neurotrophic factor is involved in metabolic sexual dimorphism. The accumulated data in this field has uncovered important aspects of the physiological and pathological control of metabolic sex-specific functions and has placed hypothalamic brain-derived neurotrophic factor as a potential target for interventions aimed at mitigating metabolic abnormalities that affect differently females and males.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytes as Metabolic Sensors Orchestrating Energy-Driven Brain Vulnerability in Alzheimer's Disease","authors":"Leyre Sánchez de Muniain,&nbsp;Paula Escalada,&nbsp;María J. Ramírez,&nbsp;Maite Solas","doi":"10.1111/jnc.70252","DOIUrl":"10.1111/jnc.70252","url":null,"abstract":"<p>Alzheimer's disease (AD), the leading neurodegenerative disorder linked to aging, emerges within a paradoxical metabolic landscape. Despite rising cellular energy demands due to accumulated damage and stress, overall energy expenditure remains stable or declines with age. The brain, acting as the central regulator, responds to hypermetabolic signals from aged tissues by activating energy-conserving mechanisms. In this scenario, astrocytes, strategically located between blood vessels and neurons, play a pivotal role as energy sensors, adapting to systemic stress and modulating brain metabolism. This review explores how astrocytes undergo metabolic reprogramming in the early stages, potentially becoming maladaptive over time, fueling neuroinflammation, oxidative stress, and accelerating AD. By understanding astrocyte energetics, we uncover new avenues for biomarkers and therapies that could transform AD treatment.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tiny Messengers, Huge Consequences: Extracellular Vesicles and mTOR Signaling in Neuroinflammation","authors":"P. Garcia-Segura,&nbsp;A. Chicote-González,&nbsp;A. Espasa-Marco,&nbsp;M. Garcia-Alcaraz,&nbsp;L. Mora-Bernabé,&nbsp;M. Abelló-Fernández,&nbsp;C. Malagelada","doi":"10.1111/jnc.70256","DOIUrl":"10.1111/jnc.70256","url":null,"abstract":"<p>Neuroinflammation plays a fundamental role in the pathogenesis of neurodegenerative disorders. Among the central regulators of this process are the mechanistic target of rapamycin (mTOR) signaling pathway and extracellular vesicles (EVs). This review discusses the bidirectional interaction between mTOR and EVs, describing their interconnection in the regulation of cellular communication and inflammatory responses in the central nervous system (CNS). On one hand, mTOR controls EV biogenesis and cargo composition, and, on the other hand, EVs also modulate mTOR activity in target cells with effects in neuronal survival, glial activation, and immune signaling. This bidirectional communication creates a feedback loop that, depending on cell context and molecular cues, may either promote neuroprotection or exacerbate neurotoxicity and inflammation.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrergic Signaling Mediation of Neurobehavioral Responses to Stress in Zebrafish","authors":"João Alphonse Apóstolo Heymbeeck,&nbsp;Eveline Bezerra de Sousa,&nbsp;Monica Lima-Maximino,&nbsp;Antonio Pereira Jr.,&nbsp;Caio Maximino","doi":"10.1111/jnc.70254","DOIUrl":"10.1111/jnc.70254","url":null,"abstract":"<p>Nitric oxide (NO) is a gaseous transmitter that is involved in the regulation of multiple behavioral processes in the brain. Here, we review the participation of this molecule in zebrafish neurobehavioral responses to stress. NO signaling pathways are considerably conserved in this species, and different pathways appear to be related to the complex regulation of behavior by this molecule. NO acts as a downstream integrator of responses to different upstream signals, including glutamate, serotonin, and inflammatory mediators; as a result, it participates in both anxiolytic and anxiogenic effects of drugs acting at different targets. There is considerable evidence for the participation of both a glutamate/NOS-1 pathway and a KCNN/NOS-2 pathway in long-term behavioral sensitization to stress in zebrafish, suggesting that this molecule regulates metaplasticity in circuits that mediate defensive responses. Important questions remain unanswered, including the relationship between NO signaling, oxidative stress, and neuroinflammation, as well as the actual mechanisms of metaplasticity in the zebrafish brain.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}