Journal of integrative neuroscience最新文献

{"title":"Small Extracellular Vesicles Derived From Mesenchymal Stem Cells Exert Neuroprotective Effect Against a Model of Dopamine Dysfunction by Inhibiting Caspase-8/Caspase-3-Mediated Apoptosis.","authors":"Songzhe He, Qi Qu, Ling Hu, Yufang Yan, Qiongqiong Wang, Yi Ouyang, Xiaofang Wang, Shaogang Qu","doi":"10.31083/JIN49659","DOIUrl":"https://doi.org/10.31083/JIN49659","url":null,"abstract":"<p><strong>Background: </strong>The precise pathological mechanisms driving Parkinson's disease (PD) progression remain incompletely understood, and there are currently no therapies that can modify the course of the disease. While mesenchymal stem cells (MSCs) hold therapeutic potential for various conditions, their clinical utility is constrained by challenges in sourcing and limited availability.</p><p><strong>Methods: </strong>This study investigated a novel therapeutic approach using trophoblast-derived mesenchymal-like stem cells (T-MSCs), which can be stably generated from commercially available embryonic stem cells, and the small extracellular vesicles (T-MSCs-sEVs) that they secrete. We explored the therapeutic effects against PD by inhibiting Caspase-8/Caspase-3-mediated apoptosis both <i>in vitro</i> and <i>in vivo</i> using experimental assays (e.g., flow cytometry (FCM) analysis, western blotting, and immunofluorescence staining).</p><p><strong>Results: </strong>The selected cytokine Clusterin was validated via G-Series Mouse Cytokine Antibody Array 4000 (GSM-CAA-4000) using ELISA kits, which revealed its involvement in apoptosis during the PD process. Moreover, T-MSCs and T-MSCs-sEVs could alleviate dopaminergic (DA) neuron damage <i>in vitro</i> and <i>in vivo</i> by inhibiting the Caspase-8/Caspase-3-mediated apoptotic pathway.</p><p><strong>Conclusions: </strong>The results suggest that T-MSCs-sEVs represent a promising biological candidate for future therapeutic strategies aimed at treating PD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"49659"},"PeriodicalIF":3.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396920","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":"Antiseizure Medications Impact Mitochondrial Ion Channels via Novel Bioenergetic and Neural Mechanisms.","authors":"Carmen Rubio, Norma Serrano-Garcia, Ricardo Pérez-Rubio, Javier Pérez-Villavicencio, Héctor Romo-Parra, Ángel Lee, Moisés Rubio-Osornio","doi":"10.31083/JIN52316","DOIUrl":"https://doi.org/10.31083/JIN52316","url":null,"abstract":"<p><p>Antiseizure medications (ASMs) have traditionally been characterized by their modulation of neuronal ion channels and synaptic processes; however, accumulating evidence indicates that numerous ASMs also directly modulate mitochondrial function. Specifically, several ASMs interact with ion channels located in both the inner and outer mitochondrial membranes, including the voltage-dependent anion channel (VDAC), the mitochondrial calcium uniporter (MCU), the mitochondrial Na⁺/Ca²⁺ exchanger (NCLX), the mitochondrial permeability transition pore (mPTP), and mitochondrial ATP-sensitive potassium channels (mitoKATP). Modulation of these channels regulates critical processes in epilepsy, including Ca²⁺ homeostasis, ATP synthesis, redox equilibrium, and susceptibility to neuronal apoptosis. Phenytoin and carbamazepine reduce voltage-dependent anion channel isoform 1 (VDAC1)-associated mitochondrial permeability by modulating the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 protein (Bcl-2) ratio; ethosuximide limits mitochondrial Ca²⁺ overload through modulation of the MCU complex; valproic acid stabilizes NCLX function and prevents mPTP opening via antioxidant mechanisms; levetiracetam contributes to preserving intracellular Ca²⁺ handling; and mitoKATP activators, including diazoxide and retigabine, promote mitochondrial membrane potential stability and reduce seizure-induced reactive oxygen species (ROS) generation. The mitochondrial effects vary according to epilepsy subtype, contributing to the attenuation of hippocampal apoptosis in temporal lobe epilepsy and thalamocortical network modulation in generalized epilepsies. In this narrative review we examine the experimental and molecular evidence demonstrating how ASMs modulate mitochondrial ion channels and how these interactions contribute to their anticonvulsant mechanisms, thereby broadening the understanding of mitochondria as key functional components in antiseizure pharmacology.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"52316"},"PeriodicalIF":3.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396968","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":"Functional Diversity of Mouse dLGN Neurons and Modulation of Their Encoding Properties by Superior Colliculus.","authors":"Xiaoying Ma, Chengyong Jiang, Wenbin Xie, Weilong Li, Qingyuan Chen, Yiheng Wang, Yuqing Chen, Junwen Luo, Su Jiang, Jiayi Zhang, Biao Yan","doi":"10.31083/JIN52032","DOIUrl":"10.31083/JIN52032","url":null,"abstract":"<p><strong>Background: </strong>The dorsal lateral geniculate nucleus (dLGN) exhibits remarkable functional diversity, yet a systematic classification of its neuronal properties and the subcortical mechanisms that modulate these representations remains to be fully elucidated.</p><p><strong>Methods: </strong>In this study, we performed a comprehensive functional mapping of the mouse dLGN using a diverse battery of visual stimuli. Neurons were grouped into clusters using unsupervised clustering of multi-dimensional response features, and the superior colliculus (SC) was pharmacologically silenced to assess its modulatory role.</p><p><strong>Results: </strong>We identified at least 33 distinct functional clusters characterized by specialized tuning for contrast, frequency, and speed, as well as direction and orientation selectivity, providing a high-dimensional atlas of dLGN diversity. SC suppression triggered a multidimensional reorganization of dLGN properties that was cluster-specific and selectively affected various functional indices, including contrast sensitivity and feature selectivity, depending on the cell group.</p><p><strong>Conclusions: </strong>These results indicate that distinct functional clusters of dLGN neurons exhibit heterogeneous modulation by SC inputs, demonstrating that collicular inputs are essential for shaping the diverse functional profiles of thalamic visual channels.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"52032"},"PeriodicalIF":3.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396941","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":"Assessing Cumulative Mental Fatigue via EEG-Based Machine Learning in a Multiday High-Intensity Contest.","authors":"Xiaodong Yang, Jie Zhou, Zhan Chen, Yufei Jing, Yawei Xie, Hao Yu, Yongjie Yao, Chunpeng Jiang, Chuantao Li","doi":"10.31083/JIN49347","DOIUrl":"https://doi.org/10.31083/JIN49347","url":null,"abstract":"<p><strong>Background: </strong>Cumulative mental fatigue poses a significant threat to safety, productivity, and health in the workplace. In this study, we aimed to establish a robust machine learning framework using optimized resting-state electroencephalography (rs-EEG) features to detect such fatigue and to validate a 4-day high-stress cognitive competition paradigm for its induction.</p><p><strong>Methods: </strong>EEG signals were recorded from participants under eyes-closed (EC) and eyes-open (EO) conditions during fatigue and recovery phases. We extracted 544 features spanning power spectral density, entropy, and nonlinear complexity. Support Vector Machine Recursive Feature Elimination (SVM-RFE) was used for feature selection. The derived model index (Mean Model Result, MMR) was correlated with a subjective sleepiness index (the Stanford Sleepiness Scale, SSS) and sleep duration.</p><p><strong>Results: </strong>Analysis of participant data identified a discriminative subset of 65 features from the EC EEG. The model achieved an accuracy of 90.37% in classifying deeply fatigued versus fully recovered states, significantly outperforming the EO-based model (86.54%). The MMR demonstrated a significant negative correlation with SSS scores (<i>r_s</i> = -0.358, <i>p</i> = 0.020) and a positive correlation with sleep duration (<i>r_s</i> = 0.494, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>The results of this study demonstrate the superior efficacy of EC rs-EEG for monitoring cumulative fatigue, establishing a quantifiable EEG-sleep relationship and supporting the practical feasibility of this framework for occupational fatigue risk assessment.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"49347"},"PeriodicalIF":3.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396938","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":"Exploring the Microbiome-Kynurenine Axis in Mild Cognitive Impairment: From Gut to Brain.","authors":"Jiaxing Zhu, Haihua Xie, Yingke Ouyang, Ting Zhu, Qianyan Liu, Weiai Liu, Shulin Xiong, Mi Liu","doi":"10.31083/JIN48660","DOIUrl":"10.31083/JIN48660","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) represents a critical prodromal stage of Alzheimer's disease. This review synthesizes current evidence to present a coherent pathological cascade driving MCI progression: gut microbiota dysbiosis (e.g., enrichment of <i>Prevotella</i> and depletion of <i>Akkermansia</i>) triggers a butyrate deficit and compromise of intestinal integrity, leading to systemic inflammation. This inflammatory milieu upregulates indoleamine 2,3-dioxygenase 1 (IDO1), shifting tryptophan metabolism toward the kynurenine pathway and resulting in the dominance of neurotoxic branches (3-hydroxykynurenine [3-HK], quinolinic acid [QUIN]) over neuroprotective kynurenic acid (KYNA). This metabolic imbalance promotes N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity, oxidative stress, and neuroinflammation, which collectively precipitate synaptic dysfunction and cognitive decline. We explicitly highlight this \"gut-immune-metabolic\" vicious cycle as the core framework of MCI pathology. Targeting this cycle through a dual strategy-restoring microbial diversity and pharmacologically inhibiting the IDO1/kynurenine 3-monooxygenase (KMO) enzymes-represents a promising therapeutic approach to delay the transition from MCI to dementia.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"48660"},"PeriodicalIF":3.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396983","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":"Efficacy and Safety of Transcranial Direct Current Stimulation on Multiple Health Outcomes in Neurological Disorders: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials.","authors":"Tianfeng Ye, Yuli Shuai, Yiwei Liu, Sibei Liu, Xinyu Tang, Wei Tian, Yujia Zhang, Yuhan Kong","doi":"10.31083/JIN47145","DOIUrl":"10.31083/JIN47145","url":null,"abstract":"<p><strong>Background: </strong>Neurological disorders are a leading cause of disability worldwide. Transcranial direct current stimulation (tDCS) is a promising therapeutic tool for neurological disorders. However, a consensus on clinical recommendations for using tDCS in patients with neurological disorders is lacking. In this umbrella review, we aimed to establish evidence-based guidance for using tDCS to treat neurological disorders.</p><p><strong>Methods: </strong>This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020. PubMed/MEDLINE, Embase, the Cochrane Library, the Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched to identify and evaluate existing systematic reviews and meta-analyses on the use of tDCS for neurological disorders. Quality was assessed using the Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. The Hartung-Knapp-Sidik-Jonkman random effects model was employed for reanalysis.</p><p><strong>Results: </strong>A total of 17 systematic reviews and meta-analyses encompassing 358 randomized controlled trials and 7160 participants were analyzed. tDCS demonstrated efficacy across seven distinct health conditions, including stroke, Parkinson's disease, Alzheimer's disease, cerebellar ataxia, fibromyalgia, disorders of consciousness, and migraine. Adverse effects were rarely reported, with the exception of mood changes associated with fibromyalgia. Our results indicated that tDCS significantly improved 34 distinct health outcomes related to these conditions.</p><p><strong>Conclusions: </strong>We found that tDCS may be a promising treatment for neurological disorders, with mild and infrequent adverse effects. Further studies are warranted to validate the therapeutic potential of tDCS in the reported neurological conditions, investigate additional neurological health outcomes, and explore the underlying mechanisms of tDCS effects. The PROSPERO Registration: CRD42024589432, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024589432.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"47145"},"PeriodicalIF":3.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396933","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 Effects of Early Postnatal Administration of R-Baclofen on Neuronal Properties in the <i>Cntnap2</i> Knockout Rat.","authors":"Hannah Pineda, Susanne Schmid","doi":"10.31083/JIN52072","DOIUrl":"10.31083/JIN52072","url":null,"abstract":"<p><strong>Background: </strong>Contactin-associated protein-like 2 (<i>Cntnap2</i>) is a highly expressed gene during development, coding for the cell adhesion molecule CASPR2. Loss-of-function of <i>Cntnap2</i> leads to a neurodevelopmental disorder that presents with the core symptoms of autism. One prominent theory to explain autism symptoms is an imbalance of excitatory and inhibitory neurotransmitters, which leads to hyper-excitability in the autistic brain. R-baclofen, a γ-aminobutyric acid (GABA_B) receptor agonist, has been shown to acutely improve autism-like symptoms in rat models of autism, including exaggerated acoustic reactivity. However, the cellular basis and long-term impact of R-baclofen treatment during development are unknown. In the present study, we explored the impact of acute R-baclofen treatment on auditory cortical neurons and whether there are lasting changes in cell excitability and synaptic signaling following time-restricted R-baclofen administration during the critical period of auditory development.</p><p><strong>Methods: </strong>R-baclofen or saline were injected daily on postnatal days (PND) 14-21 and whole-cell patch clamp recordings were performed on pyramidal neurons in brain slices of the auditory cortex of juvenile (PND25-33) and adult (PND70-90) <i>Cntnap2</i> wild-type and knockout rats.</p><p><strong>Results: </strong>While acute R-baclofen application led to the expected reduction in cell excitability, early-life exposure to R-baclofen induced lasting changes in neuronal membrane properties and excitability. However, these effects were not uniformly beneficial, as in some instances they exacerbated the knockout phenotype and induced unwanted effects in wild-type neurons.</p><p><strong>Conclusions: </strong>The study shows that drug exposure in early age can change the developmental trajectory of the auditory system, indicating both opportunities and risks when considering early drug intervention.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 6","pages":"52072"},"PeriodicalIF":3.3,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396915","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":"Activation of the p62/Keap1/Nrf2 Pathway Protects Against Ferroptosis in Cerebral Ischemia-Reperfusion Injury.","authors":"Canwen Liu, Xuanyi Dong, Biao Tang","doi":"10.31083/JIN48011","DOIUrl":"10.31083/JIN48011","url":null,"abstract":"<p><strong>Background: </strong>Protein p62 interacts with Kelch-like ECH-associated protein 1 (Keap1) competitively, triggering the oxidative stress response mediated by NF-E2-related factor 2 (Nrf2) and preventing ferroptosis in SH-SY5Y cells. Emerging evidence implicates that this regulatory axis may confer neuroprotection against cerebral ischemia-reperfusion injury (CIRI). The current investigation was designed to elucidate whether the p62/Keap1/Nrf2 signaling pathway contributes to the amelioration of CIRI through modulation of ferroptosis.</p><p><strong>Methods: </strong>In SH-SY5Y cells, we used an oxygen-glucose deprivation/reperfusion (OGD/R) paradigm. In Sprague-Dawley rats, we used a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Through these models, we investigated the effects of p62/Keap1/Nrf2 pathway activation. Additionally, we used <i>in vitro</i> experiments to analyze ferroptosis markers, cell damage, and the expression of pathway proteins. We injected the p62-overexpressing lentivirus into SH-SY5Y cells and the lateral ventricle of rats subjected to MCAO/R. Finally, we investigated the effects of an Nrf2 activator and a ferroptosis inhibitor.</p><p><strong>Results: </strong>Nrf2 negatively regulated OGD/R-triggered ferroptosis in SH-SY5Y cells by increasing glutathione peroxidase 4 (GPX4) expression and decreasing acyl-CoA synthetase long-chain family member 4 (ACSL4) levels. p62 overexpression in cells enhanced the interaction between Keap1 and p62, activating Nrf2 and protecting against OGD/R-triggered ferroptosis. Activating the p62/Keap1/Nrf2 signaling pathway <i>in vivo</i> reduced the brain injury area, decreased neuromotor functional impairment, and decreased the expression of ferroptosis markers in rats.</p><p><strong>Conclusions: </strong>Activation of the p62/Keap1/Nrf2 signaling pathway reduces ferroptosis and alleviates CIRI. This protective mechanism provides novel directions for investigating the pathological mechanisms of CIRI.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"48011"},"PeriodicalIF":3.3,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054817","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":"\"See What I Mean?\" Linguistic Digital Markers of Cognitive Decline in Nursing Home Residents.","authors":"Sonja Cecchetti, Andrew T Duchowski, Marco Cavallo","doi":"10.31083/JIN49652","DOIUrl":"10.31083/JIN49652","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cognitive decline in nursing homes is often under-recognized. Access to specialized neuropsychological assessments, which involve detailed evaluations of how the brain influences behavior and thinking, is often limited. In this study, we examined the feasibility of administering an ecological reading task, involving reading activities that imitate real-life situations, in a real-world nursing home setting. We also explored whether reading-derived linguistic metrics and measures of language use during reading, along with an eye-tracking component that monitored participants' eye movements, were associated with cognitive impairment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This cross-sectional observational pilot study included 60 nursing home residents aged 65 years or older, classified as either cognitively impaired (CI, n = 30) or healthy control (HC, n = 30) based on neuropsychological profiles and clinical evaluations. All participants completed the Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), Barthel Index, and Cognitive Reserve Index questionnaire (CRIq). The reading task involved reading aloud a 177-word Italian passage followed by eight comprehension questions. Primary outcomes were total reading errors (TRE), total comprehension errors (TCE), and words per minute (WPM). Eye-tracking data (Gazepoint GP3, 60 Hz) were available for a subsample with usable calibration and validation data (CI: n = 26; HC: n = 24). Analyses included descriptive comparisons, covariate-adjusted generalized linear models, receiver operating characteristic (ROC) analyses, and partial Spearman correlations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All 60 participants completed the task. Usable audio recordings were obtained for everyone, and usable eye-tracking data were available for 50 participants. The CI group showed higher TRE and TCE, lower WPM, and longer reading times compared with the HC group. In models adjusted for gender, age, education, GDS, Barthel Index, and CRIq, TCE showed the strongest association with CI status (odds ratio [OR] = 11.108, 95% CI 2.662-246.186, &lt;i&gt;p&lt;/i&gt; = 0.024), and TRE was also associated with CI status (OR = 1.238, 95% confidence interval [CI] 1.054-1.629, &lt;i&gt;p&lt;/i&gt; = 0.045). ROC analyses showed high areas under the curve (AUCs) for TCE (0.982), TRE (≈0.95), and audio-based WPM (0.936). In the eye-tracking subsample, timing-related measures also showed good discrimination (AUC = 0.960 for eye tracking [ET]-WPM; 0.942 for ET-Total Reading Time), whereas conventional first-order oculomotor metrics did not differ significantly between groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;An ecological reading task was feasible within a nursing home setting. It generated reading-derived linguistic metrics linked to cognitive impairment and broader cognitive-functional status. Measures related to ","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"49652"},"PeriodicalIF":3.3,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054779","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":"STING Mediates Necroptosis in Hippocampal Neurons of Mice With Sepsis-Associated Encephalopathy.","authors":"Xiaofeng Guo, Baocheng Cang, Yunhu Bai, Ding Zhang, You Wu, Tongwen Sun, Xijing Zhang","doi":"10.31083/JIN50074","DOIUrl":"10.31083/JIN50074","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated encephalopathy (SAE) is a common and severe neurological syndrome induced by sepsis and characterized by brain dysfunction. The incidence of SAE is as high as 76%. After onset, the mortality rate is as high as 60%. Even if patients survive, about 20% have long-term cognitive impairment. At present, the exact pathogenesis of SAE remains unknown. Our results showed that necroptotic protein was obviously elevated in the hippocampus of SAE mice, but the internal mechanism was still unclear. The stimulator of interferon gene (STING) protein has been reported to be a key molecule in the regulation of programmed cell death. However, the critical role of STING in the progression of SAE remains elusive. We explored the mechanism by which STING regulates hippocampal neuronal necroptosis in SAE.</p><p><strong>Methods: </strong>A cannula was embedded into the lateral ventricle of mice, and mixed lineage kinase domain-like protein (MLKL) inhibitor necrosulfonamide (NSA) and STING inhibitor C-178 were injected. The motor ability and memory function of mice after cecal ligation and puncture (CLP) were assessed by the open field test (OFT) and barnes maze test (BMT), respectively. The expression and distribution of ^S345p-MLKL and ^S366p-STING proteins in the hippocampal region of SAE mice were analyzed, and the expression levels of ^S366p-STING/STING, ^S232p-receptor-interacting protein kinase 3 (RIPK3)/RIPK3, ^S345p-MLKL/MLKL, and ^S166p-RIPK1/RIPK1 proteins in the hippocampal tissue of SAE mice were examined. Co-immunoprecipitation (CO-IP) was used to detect the relationship between STING and RIPK3 protein.</p><p><strong>Results: </strong>The surviving mice after CLP had cognitive dysfunction. The hippocampal tissues of SAE mice showed upregulated expression of ^S232p-RIPK3/RIPK3, ^S345p-MLKL/MLKL, and ^S166p-RIPK1/RIPK1 proteins. Mice in the CLP+NSA group showed better cognitive performance than the mice in the CLP+dimethyl sulfoxide (DMSO) group. The results showed that the expression of ^S366p-STING protein was elevated in neurons of the hippocampal cornu ammonis 1 (CA1) region in SAE mice, and there was an interaction between STING and RIPK3 proteins. STING inhibitor C-178 inhibited the protein expression level of ^S232p-RIPK3/RIPK3 and ^S345p-MLKL/MLKL and alleviated SAE mice with cognitive dysfunction.</p><p><strong>Conclusions: </strong>STING is implicated in the development of cognitive dysfunction in SAE by regulating necroptosis in hippocampal neurons. Inhibition of the STING pathway reduced necroptosis-related protein expression and partially improved BMT performance. This result provides a new potential therapeutic target for the prevention and treatment of SAE.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 5","pages":"50074"},"PeriodicalIF":3.3,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054911","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}