Journal of integrative neuroscience最新文献

{"title":"Preclinical Study of the Neuroprotective Effects of Pharmacological Agent-Modulators of HSP70 After Intrauterine Hypoxia.","authors":"Igor Belenichev, Olena Aliyeva, Nina Bukhtiyarova, Victor Ryzhenko, Sergiy Oliynyk, Suyeon Lee, Kyu-Ho Yi","doi":"10.31083/JIN51482","DOIUrl":"https://doi.org/10.31083/JIN51482","url":null,"abstract":"<p><strong>Background: </strong>Chronic intrauterine hypoxia (IUH) is a cause not only of early postnatal mortality but also of delayed central nervous system (CNS) impairments in offspring, including increased risks of acute cerebrovascular disorders, epilepsy, and neurodegenerative diseases. The above necessitates the urgent development of targeted neuroprotective strategies for newborns following IUH. The aim of the present study was to evaluate the neuroprotective effects of the 70 kDa heat shock protein (HSP70) modulators (angiolin, thiotriazolin, cerebrocurin, tamoxifen, glutaredoxin, and heat shock factor 1 (HSF-1)), as well as reference drugs, based on their impact on molecular markers of endothelial dysfunction (vascular endothelial growth factor A (VEGF-A), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrotyrosine), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and caspase-8 in the brains of offspring after IUH at 1 and 2 months of age.</p><p><strong>Methods: </strong>Chronic hemic IUH was modeled in pregnant rats by daily administration of sodium nitrite (50 mg/kg, intraperitoneally) on days 16-21 of pregnancy. The male offspring were treated with the study drugs for 30 days starting on P1. Brain homogenates of offspring at P30 and P60 were analyzed using enzyme-linked immunosorbent assay (ELISA) for VEGF-A, eNOS, iNOS, nitrotyrosine, BDNF, NGF, and caspase-8.</p><p><strong>Results: </strong>IUH caused persistent endothelial dysfunction, characterized by decreased VEGF and eNOS levels, and nitrosative stress, associated with increased iNOS and nitrotyrosine levels. These changes were accompanied by decreased neurotrophin levels, including BDNF and NGF, and increased caspase-8 levels. Course administration of angiolin, cerebrocurin, HSF-1, thiotriazolin, and glutaredoxin improved the eNOS/iNOS balance, increased VEGF levels, and decreased nitrotyrosine levels, with the effect persisting until P60. Cerebrocurin and angiolin demonstrated the strongest recovery of neurotrophic factors (normalization or exceeding normal BDNF/NGF levels by P60) and effectively suppressed caspase-8 to near-normal levels. A positive correlation was established between BDNF, NGF, and HSP70 levels.</p><p><strong>Conclusions: </strong>Pharmacological modulators of HSP70 provide effective multimodal neuroprotection due to endothelioprotective and neurotrophic effects. Angiolin and Cerebrocurin demonstrate significant therapeutic potential, offering a promising strategy for mitigating the long-term neurological sequelae of IUH.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 7","pages":"51482"},"PeriodicalIF":3.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Orchestral String Learning and Event-Related Potentials of Inhibitory Control in Children From Disadvantaged Communities.","authors":"Taylor Hirsch, Amedeo D'Angiulli","doi":"10.31083/JIN45659","DOIUrl":"10.31083/JIN45659","url":null,"abstract":"<p><strong>Background: </strong>Children from low socioeconomic status (SES) backgrounds are at increased risk for delays in executive function (EF), particularly inhibitory control and attentional regulation. Orchestral string music training is a complex multisensory activity that repeatedly engages executive control systems, yet its neurophysiological mechanisms remain insufficiently understood. In this study we examined whether prolonged string training is associated with enhanced neural dynamics underlying inhibitory control in socioeconomically disadvantaged children.</p><p><strong>Methods: </strong>We re-analyzed 32-channel electroencephalography (EEG) data from an auditory Go/NoGo task in 20 children aged 9-12 years (11 with ≥4 years of orchestral string training; 9 controls). Event-related potentials (ERPs) were extracted using a data-driven vincentization pipeline. Group differences were assessed using mixed-model ANOVAs and topographic analyses.</p><p><strong>Results: </strong>Musically trained children showed significantly larger NoGo-related ERP amplitudes across N1-N2, P300, N400, and late positive components, with maximal effects over right frontocentral and temporoparietal regions (median Cohen's f = 0.78, median <i>p</i> = 0.005, median upper bound Bayesian Factor = 24.17). These neural differences emerged despite comparable behavioral performance between groups.</p><p><strong>Conclusions: </strong>Findings suggest that orchestral string training is associated with more efficient recruitment of inhibitory-attentional networks in children facing socioeconomic adversity. These effects align with enhanced fronto-parietal integration and neural efficiency principles, consistent with Adaptive Resonance Theory and Parieto-Frontal Integration Theory frameworks, supporting its potential as a scalable intervention for executive function development.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"45659"},"PeriodicalIF":3.3,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Relationship Between Gastrointestinal Diseases and Neural Nuclei in Animal Models.","authors":"Jing Xiong, Jiake Zou, Xiao Deng, Dan Wang, Yifan Li, Zhaoxuan He","doi":"10.31083/JIN48047","DOIUrl":"10.31083/JIN48047","url":null,"abstract":"<p><p>Gastrointestinal (GI) diseases are manifestations of abnormal brain-gut interactions, which are closely related to brain functions. Systematic sorting of the central mechanisms related to GI functions is of great clinical significance for preventing and treating GI disorders. We therefore conducted a literature search in the PubMed and Web of Science databases, spanning publications from January, 1975 to March 31, 2025. A total of 398 articles were retrieved, with three of these identified through supplementary searches. After screening, 56 animal studies were included for analysis. The findings indicate that central regulation of GI function is primarily mediated by the frontal and cingulate cortices. Subcortical nuclei appear to be more strongly associated with GI activity than cortical regions, particularly nuclei within the hypothalamus, brainstem, hippocampal gyrus, central amygdala, and thalamus. The hypothalamic-pituitary-adrenal axis plays a crucial role in the regulation of GI function via neuroendocrine pathways and has been extensively studied. However, most studies to date have focused on individual brain regions or specific nuclei, with limited investigation into integrated neural circuits or axis-level mechanisms. Recent advances in neuroscience techniques have paved the way for future studies to more comprehensively investigate cortical-subcortical brainstem multilevel neural circuits and cross-organ regulation of central-GI interactions, contributing to a deeper understanding of the underlying mechanisms of GI-brain interactions.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"48047"},"PeriodicalIF":3.3,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow-Derived Mesenchymal Stromal Cells Alleviate Bone Cancer Pain by Modulating Microglial Polarization: Involvement of the Nrf2/HO-1 Pathway.","authors":"Xinyu Lu, Penghui Ren, Jing Zhang, Ping Wu, Qingping Wen","doi":"10.31083/JIN47234","DOIUrl":"10.31083/JIN47234","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dysregulated polarization of spinal microglia is a key contributor to the pathophysiology of bone cancer pain (BCP). Bone marrow-derived mesenchymal stromal cells (BMSCs) have demonstrated significant analgesic and microglial-modulatory effects in various pain models. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is implicated in the regulation of microglial polarization. However, the specific role and mechanistic basis of intrathecally administered BMSCs in influencing spinal microglial polarization during BCP remain to be fully clarified. In this study, we investigated the impact of intrathecal administration of BMSCs on spinal microglial polarization in a rat model of BCP, and assessed the potential contribution of the Nrf2/HO-1 signaling pathway to this process.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In a rat model of BCP, animals received three intrathecal injections of 2 × 10&lt;sup&gt;6&lt;/sup&gt; BMSCs at every other day. Pain behavioral tests, including measurements of the 50% paw withdrawal threshold (PWT) and the number of spontaneous flinches (NSF), were assessed before and after BMSCs administration. The CatWalk automated gait analysis system was employed to quantify BMSC-mediated amelioration of BCP-associated locomotor deficits. Protein expression levels of the pro-inflammatory microglial markers cluster of differentiation 86 (CD86) and inducible nitric oxide synthase (iNOS), along with the anti-inflammatory markers CD206 and Arginase-1 (Arg-1), as well as key components of the Nrf2/HO-1 signaling pathway, were measured in spinal cord tissues using Western blot and immunofluorescence staining. In addition, a non-contact co-culture system of BMSCs and lipopolysaccharide (LPS)-activated BV2 cells was established. The expression of CD86, iNOS, CD206, Arg-1, and pathway components, together with the mRNA levels of the inflammatory cytokines interleukin (IL)-1β and IL-10, were analyzed via Western blot, immunofluorescence, and quantitative real-time PCR (RT-qPCR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Intrathecal injection of BMSCs significantly alleviated established pain behaviors in BCP rats, as evidenced by increased 50% PWT, reduced NSF, and normalized gait parameters. At the molecular level, BMSC treatment downregulated the spinal cord expression of the pro-inflammatory markers CD86 and iNOS while concurrently upregulating the anti-inflammatory markers CD206 and Arg-1. In the co-culture system, BMSC enhanced the activation of the Nrf2/HO-1 signaling pathway within LPS-stimulated BV2 cells. This enhancement was associated with a reduction in the expression of CD86 and iNOS, an increase in CD206 and Arg-1, decreased levels of IL-1β, and elevated levels of IL-10.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Intrathecal administration of BMSCs effectively attenuates pain in BCP rats by shifting spinal microglial polarization from a pro-inflammatory toward an anti-inflammatory phenotype","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"47234"},"PeriodicalIF":3.3,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Zhang et al. Caudate-Centric Triphasic Network Reconfiguration Characterizes the Early Progression of Cognitive Impairment in Parkinson's Disease: A Simultaneous PET/fMRI Study. Journal of Integrative Neuroscience. 2026; 25(2): 46634.","authors":"Wenli Zhang, Guoyang Li, Fengju Mao, Hong Zhao, Long Zhao, Lei Liang, Yutong Guo, Chang Sun, Yang Yang, Xiangcheng Wang, Xiaoguang Luo","doi":"10.31083/JIN55311","DOIUrl":"10.31083/JIN55311","url":null,"abstract":"","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"55311"},"PeriodicalIF":3.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Frequency Repetitive Transcranial Magnetic Stimulation Improves Oxidative Stress, Iron Metabolism, and Synaptic Plasticity in the Visual Cortex of Amblyopic Rats: Association With the NRF2/GPX4 Pathway.","authors":"Qin Li, Yinyin You, Qing Lu, Yunchun Zou, Xiong Yang, Haorong Wang, Wenchuan Liao, Zhe Li, Lingjun Wei, Weiqi Song","doi":"10.31083/JIN48602","DOIUrl":"10.31083/JIN48602","url":null,"abstract":"<p><strong>Background: </strong>Amblyopia is a neurodevelopmental disorder with limited treatment efficacy after the developmental critical period. Repetitive transcranial magnetic stimulation (rTMS) improves visual perception in patients with amblyopia, although its specific mechanism remains unclear. In this study, we investigated whether rTMS improves abnormal ocular dominance (OD) distribution in monocular deprivation (MD) amblyopic rats by modulating oxidative stress, iron metabolism, and synaptic plasticity through the nuclear factor erythroid 2-related factor 2/glutathione peroxidase-4 (NRF2/GPX4) pathway.</p><p><strong>Methods: </strong>Sprague-Dawley (SD) rats were randomly assigned to four groups (n = 20 each): normal control+rTMS (NC+rTMS), NC+sham stimulation (NC+sham), MD+sham, and MD+rTMS. The rTMS groups received 20-Hz rTMS treatment for 28 consecutive days. Visual function was assessed using flash visual evoked potentials (F-VEP). The morphological structure of the visual cortex, synaptic function, oxidative stress levels, iron metabolism, and expression of NRF2/GPX4 were analyzed using histopathological staining, transmission electron microscopy (TEM), biochemical assay, and molecular biology experiments. Statistical analyses were performed using repeated-measures analysis of variance (ANOVA) and two-way ANOVA. Bonferroni post-hoc tests were used afterward.</p><p><strong>Results: </strong>Following rTMS treatment, the contralateral vs. ipsilateral value (C/I values) in the MD+rTMS group were higher than baseline (<i>p</i> < 0.0001). Compared with the MD+sham group, rTMS alleviated visual cortex synaptic ultrastructural damage and upregulated postsynaptic density protein 95 (PSD-95) and brain-derived neurotrophic factor (BDNF) levels in MD rats (<i>p</i> = 0.016, <i>p</i> = 0.041). The MD+rTMS group showed significantly decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels (<i>p</i> < 0.05, <i>p</i> < 0.0001) and increased glutathione (GSH) content (<i>p</i> < 0.0001) in comparison with the MD+sham group. Additionally, rTMS elevated NRF2, GPX4, and ferroportin-1 (FPN1) expression in the MD group (all <i>p</i> < 0.01) and reduced ferrous iron (Fe²⁺) accumulation (<i>p</i> < 0.01) relative to the MD+sham group.</p><p><strong>Conclusions: </strong>High-frequency rTMS improves abnormal OD distribution in amblyopic rats, an effect associated with the upregulation of NRF2/GPX4 pathway protein expression, reduced oxidative stress, restored iron metabolism, and enhanced synaptic plasticity in the visual cortex. This finding offers novel insights into the mechanisms of rTMS and the pathology of amblyopia.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"48602"},"PeriodicalIF":3.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glymphatic-Related Alterations in Major Depressive Disorder and Treatment-Resistant Depression: Imaging Proxies, Mechanistic Links, and Therapeutic Opportunities.","authors":"Tommaso Barlattani, Chiara D'Amelio, Arianna Baschieri, Edoardo Trebbi, Filippo Trebbi, Alessandro Rossi, Vassilis Martiadis, Valerio Ricci, Carmine Tomasetti, Domenico De Berardis, Francesca Pacitti","doi":"10.31083/JIN51052","DOIUrl":"https://doi.org/10.31083/JIN51052","url":null,"abstract":"<p><p>Major depressive disorder is increasingly conceptualized as a condition involving brain network dysfunction, neuroimmune imbalance, sleep-circadian disruption, hypothalamic-pituitary-adrenal (HPA)-axis dysregulation, monoaminergic arousal instability, and impaired synaptic plasticity. In parallel, the glymphatic system has emerged as a plausible integrative mechanism linking these domains, because it is a glia-dependent pathway supporting cerebrospinal fluid-interstitial fluid exchange and metabolic-waste clearance, with activity strongly modulated by deep non-rapid eye movement (NREM) sleep. This narrative review synthesizes evidence that glymphatic-related magnetic resonance imaging (MRI) proxies, particularly diffusion tensor imaging along the perivascular space (DTI-ALPS), are altered in depression, while emphasizing that DTI-ALPS is an indirect marker of perivascular diffusion rather than a direct measure of glymphatic flow. We define four key research gaps: scarcity of treatment-resistant depression (TRD)-specific cohorts, regional and technical heterogeneity across MRI studies, and uncertainty about causal direction relative to sleep disturbance and inflammation. Altered indices appear to relate to fatigue, psychomotor retardation, cognitive impairment, rumination, suicidality, systemic inflammation, oxidative stress, and HPA-axis dysregulation. We integrate opposite-direction findings, including elevated ALPS in drug-naive somatic depression, into a state- and subtype-dependent working model rather than a unidirectional dysfunction framework. Therapeutic implications are organized by target specificity, including sleep-dependent clearance, perivascular exchange, aquaporin-4 (AQP4) polarization, vascular pulsatility, and neuroimmune modulation. We propose falsifiable predictions and negative-control analyses to distinguish a glymphatic-related model from additive effects of insomnia, inflammation, and vascular risk. Overall, the current evidence supports a cautious translational framework for biomarker-informed trials in TRD-relevant phenotypes rather than a validated diagnostic biomarker.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"51052"},"PeriodicalIF":3.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages and Limitations of a Systemic and Ecological Assessment of Executive Functions in Children and Adolescents.","authors":"Mélissa Weisse, Virginie Dardier, Solenne Scotto di Vettimo, Véronique Tsimba, Nolwenn Troles, Anne-Sophie Douguet, Virginia Jouan, Agnès Lacroix","doi":"10.31083/JIN47025","DOIUrl":"https://doi.org/10.31083/JIN47025","url":null,"abstract":"<p><p>Executive functions (EFs) are high-level functions of human cognition and have been studied since the early 20th century. The evolution of theoretical models of EFs highlights the importance of taking into account all systemic influences, whether biological, environmental, or individual, when assessing these functions, particularly in children. This indicates the necessity to propose an integrative perspective for evaluating EFs. To do so, we drew on Bronfenbrenner's ecosystemic model to underline the importance of an ecological assessment. This article reviews the arguments in favor of the ecological assessment of EFs and acknowledged their limitations. The arguments came from (a) the biological level-recognizing that cerebral architecture, particularly the prefrontal cortex, which underlies EFs and its development with age encourages us to reconsider inter-individual differences, and (b) the environmental level-considering the influence of the family, educational, or even cultural system enables us to contextualize and take a step back from performance. The relationship between cold and hot executive functions was also considered. The development of ecological assessment tools, closer to the strategies and processes spontaneously implemented in everyday life, may lead to a more appropriate assessment of executive functioning, and thus to increasingly tailored support.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"47025"},"PeriodicalIF":3.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Correlates of Diagnostic-Relevant Emotional Processing in Schizophrenia and Major Depressive Disorder: Insights from a Replication of fMRI and Self-Report Scales.","authors":"Elijah Agoalikum, Hongzhou Wu, Benjamin Klugah-Brown, Ping Wang, Yingqian Zhang, Stefania Ferraro, Licia Pacheco Luna, Andre F Carvalho, Mengge Li, Chenghui Yang, Michael Maes","doi":"10.31083/JIN49751","DOIUrl":"https://doi.org/10.31083/JIN49751","url":null,"abstract":"<p><strong>Background: </strong>Accurate differentiation between major depressive disorder (MDD) and schizophrenia (SZ) remains a clinical challenge due to overlapping symptoms and limitations of traditional diagnostic methods. Integrating neurobiological markers, especially functional magnetic resonance imaging (fMRI), with clinical assessments holds promise for improving diagnostic specificity. Recently, a translational cross-validation paradigm integrated the von Zerssen Paranoid-Depression Scale (a clinical self-assessment scale) with simultaneous fMRI data acquisition to cross-validate evaluations of psychopathology using neuroimaging techniques, allowing direct comparison of subjective symptom-related processing with corresponding neural activation patterns. Hence, we sought to replicate this method in an independent Chinese cohort.</p><p><strong>Methods: </strong>A sample of 62 participants, comprising 32 MDD and 30 SZ patients, underwent task-based fMRI scanning using a paradigm with statements of diagnostically neutral (DN), depressive-specific (DS), and paranoid-specific (PS) content. After preprocessing, the number was reduced to 57 (30 MDD and 27 SZ). Neural responses were analyzed using the PS versus DS contrast to isolate paranoia- versus depression-related processing. Brain activation patterns were compared across the two patient groups. Mixed-effects Analysis of Variance (ANOVA) was used to test main effects and interactions.</p><p><strong>Results: </strong>In SZ relative to MDD, processing paranoia-relevant content (PS > DS) was associated with greater activation in the bilateral supplementary motor area (SMA), left middle cingulate cortex (MCC), right precentral gyrus, and right superior frontal gyrus, indicating differential neural engagement during paranoia-specific processing. The second-level mixed-effects ANOVA revealed a significant main effect of condition (PS versus DS) across both groups in the precuneus/calcarine cortex, left frontal cortex, and hippocampal regions, indicating task-related modulation of neural activity. Importantly, a significant group × condition interaction was identified in fronto-cingulate, motor, temporal, and prefrontal regions, suggesting differential neural responses to paranoia-related processing between SZ and MDD.</p><p><strong>Conclusions: </strong>Integrating task-based fMRI with clinical self-assessment scales offers a robust approach to delineate neurofunctional differences between SZ and MDD. Combining self-report scales with fMRI data contributes to the development of objective neurobiological markers, enhances the reliability of the differential diagnosis, and provides a neurobiological basis for more precise clinical assessments.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"49751"},"PeriodicalIF":3.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Serpinb2</i> is Upregulated in Dorsal Root Ganglia and Associated With Neuroinflammatory Changes in a Mouse Model of Neuropathic Pain.","authors":"Doudou Zhao, Ziye Jia, Ali Zou, Xinyu Zhang, Enjun Lei","doi":"10.31083/JIN50669","DOIUrl":"10.31083/JIN50669","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain (NP) is a refractory chronic pain condition that severely impairs quality of life, while currently available treatments often provide insufficient relief. Emerging evidence indicates that neuroinflammation in the dorsal root ganglion (DRG) is critically involved in the development and maintenance of NP; however, the molecular mechanisms responsible for this process remain to be elucidated. The aim of this study was to identify and validate key genes involved in NP and to investigate their potential as therapeutic targets.</p><p><strong>Methods: </strong>Integrated bioinformatic analyses were performed using multiple DRG transcriptomic datasets derived from a spared nerve injury (SNI) model. Differential expression analysis and weighted gene co-expression network analysis were used to identify NP-associated genes, followed by functional enrichment analyses. Experimental validation was subsequently conducted in an SNI mouse model. Mechanical sensitivity and anxiety-like behaviors were assessed, and the expression of candidate genes in ipsilateral L4-L6 DRGs was examined using quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry.</p><p><strong>Results: </strong>Eight candidate genes associated with NP were identified through integrated bioinformatic analyses. Among these, serpin family B member 2; plasminogen activator inhibitor-2, PAI-2 (<i>Serpinb2</i>) was consistently upregulated across datasets. The well-established pain-related gene sodium voltage-gated channel alpha subunit 3 (<i>Scn3a</i>) was included as a reference. <i>Serpinb2</i>-associated gene networks were primarily enriched in inflammatory and immune-related pathways. SNI mice developed significant mechanical allodynia and anxiety-like behaviors. Consistent with these findings, <i>Serpinb2</i> expression was significantly increased in DRG tissues at both the mRNA and protein levels.</p><p><strong>Conclusions: </strong><i>Serpinb2</i> may represent a previously underappreciated molecule associated with DRG neuroinflammation in NP and may serve as a potential target for further investigation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"50669"},"PeriodicalIF":3.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}