Journal of integrative neuroscience最新文献

{"title":"Paraventricular Hypothalamic GLP-1R Neurons Mediate Propofol-Induced Suppression of Food Intake.","authors":"Jun Liang, Mingzhan Yin, Yang Su, Libo Zhang, Yong Han","doi":"10.31083/JIN52398","DOIUrl":"https://doi.org/10.31083/JIN52398","url":null,"abstract":"<p><strong>Background: </strong>Propofol is a widely used intravenous anesthetic, yet its impact on post-anesthetic feeding remains poorly characterized. The paraventricular nucleus of the hypothalamus (PVN) plays a key role in satiety regulation via glucagon-like peptide-1 receptor (GLP-1R) signaling. This study investigated whether PVN^GLP-1R neurons mediate propofol-induced suppression in food intake.</p><p><strong>Methods: </strong>Food intake was measured in wild-type mice following different doses of propofol (25, 50, 100 mg/kg, i.p.) under different conditions (hunger, day and night). The neuronal activation during the period of feeding suppression by anesthesia was assessed via c-Fos immunohistochemistry. In <i>Glp1r-Cre</i> mice, PVN^GLP-1R neurons were selectively activated or inhibited using optogenetics to determine their role in post-anesthetic feeding behavior. Fiber photometry with the calcium indicator GCaMP8m was used to record their activity in response to feeding onset during the recovery. Neural circuits were mapped using rabies virus (retrograde tracing) and synaptophysin-based virus (anterograde tracing).</p><p><strong>Results: </strong>An anesthetic dose of propofol (100 mg/kg, i.p.) suppressed food intake, regardless of circadian phase or metabolic state, whereas subanesthetic doses of propofol yielded inconsistent results depending on different scenarios. Propofol anesthesia increased c-Fos expression in PVN^GLP-1R neurons. Fiber photometry revealed that propofol abolished the physiological decrease in PVN^GLP-1R neuronal activity during food intake. The optogenetic activation of these neurons suppressed food intake, whereas inhibition promoted food intake in the post-anesthetic recovery period. Viral tracing revealed the upstream and downstream targets of PVN^GLP-1R neurons and confirmed bidirectional connections between PVN^GLP-1R neurons and the key appetite-related nuclei, including the lateral septum (LS), paraventricular thalamus (PVT), arcuate nucleus (ARC) and nucleus tractus solitarius (NTS).</p><p><strong>Conclusions: </strong>PVN^GLP-1R neurons are essential mediators of the propofol-induced suppression of food intake.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52398"},"PeriodicalIF":3.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081140","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":"Toward a Developmental Timing Framework for Autism: Linking Hemispheric Asymmetry, Motor Organization, and Motor-Social Coupling.","authors":"Gerry Leisman, Robert Melillo","doi":"10.31083/JIN54429","DOIUrl":"https://doi.org/10.31083/JIN54429","url":null,"abstract":"<p><p>Early behavioral features associated with autism spectrum disorder (ASD) are frequently examined within separate motor, sensory, and social domains rather than as interacting components of a developing neurobiological system. In this article, we present a hypothesis-driven conceptual framework proposing that variation in developmental timing and coordination across neural, motor, and interpersonal systems may contribute to differences in early social developmental trajectories. Drawing on evidence from fetal, infant, and early childhood development, we consider how hemispheric specialization, interhemispheric coordination, oscillatory synchronization, corticalization of motor control, and dyadic interaction timing may jointly influence the emergence of motor organization and social engagement. From this perspective, persistent primitive reflex expression, atypical motor asymmetry, increased motor variability, and differences in dyadic synchrony are discussed as candidate developmental indicators that may reflect broader variation in neural timing and coordination. Within this framework, we further consider how genetic, neurobiological, and environmental factors associated with ASD risk may converge on developmental timing processes expressed through neural communication, motor regulation, and social interaction. Rather than proposing a deterministic causal sequence, the present account examines how variation in motor-social interaction may influence opportunities for social learning through recurrent cycles of action, perception, prediction, and caregiver feedback. We advance a set of empirically testable developmental hypotheses linking neural timing measures, motor organization indices, reflex integration profiles, and dyadic interaction metrics within prospective longitudinal research designs. Specifically, the framework predicts that variation in early neural timing and coordination will be associated with differences in motor organization and motor-social coupling, which may in turn relate to later social developmental outcomes. By emphasizing developmental timing, coordination, and reciprocal interaction across neural, motor, and interpersonal systems, this conceptual framework is intended not as a causal account of ASD, but a hypothesis-generating developmental model that organizes existing evidence while generating explicit, empirically testable predictions regarding relationships among neural timing, motor organization, and early social interaction.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"54429"},"PeriodicalIF":3.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080528","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":"Human Astrocytes Express Functional Protease-Activated Receptors that Increase Their Reactive Phenotype Under Certain Culture Conditions.","authors":"Aparna Maruvada, Trevor J Bushell","doi":"10.31083/JIN55298","DOIUrl":"https://doi.org/10.31083/JIN55298","url":null,"abstract":"<p><strong>Background: </strong>Protease-activated receptors are G protein-coupled receptors with a novel activation mechanism by which proteases cleave the N-terminus revealing a tethered ligand that binds to the second extracellular loop leading to receptor activation. We have previously shown that protease-activated receptor 2 (PAR2) activation impairs hippocampal synaptic transmission and is neuroprotective in <i>in vitro</i> excitotoxic assays, both of which are astrocyte-dependent. We have also shown that AC264613, a blood-brain barrier-permeable PAR2 activator, results in behavioural changes associated with depression-like behaviour and recently revealed that AC264613 reduces astrocyte reactivity and amyloid load in a mouse model of amyloid pathology. However, whether functional protease-activated receptors are present in human astrocytes and if they alter their reactivity state is unknown.</p><p><strong>Methods: </strong>Commercially available human astrocytes were cultured in serum and serum-free media, and the presence of functional PARs was investigated using standard Ca²⁺ imaging techniques. Immunocytochemistry was used to examine the consequence of PAR activation on their reactive phenotype.</p><p><strong>Results: </strong>We reveal that functional PAR1 and PAR2 are present in commercially available human astrocytes. Their activation increased glial fibrillary acidic protein (GFAP) expression only after short-term culture but did not affect complement component 3 (C3) or guanylate-binding protein 2 (Gbp2) expression under any conditions tested. In contrast, no change in reactivity was observed following exposure to inflammatory stimuli.</p><p><strong>Conclusion: </strong>Overall, these data highlight that human astrocytes express functional PARs, but their activation may result in different phenotypic changes from those seen in mouse astrocytes.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"55298"},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081117","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":"LRP1 in Ischemic Stroke: From CNS Homeostasis to Ischemic Injury and Repair.","authors":"Yu-Jie Zhai, Jia-Qi Jiao, Ze-Yu Wang, Jun-Hong Guo, Yan-Ying Fan","doi":"10.31083/JIN53774","DOIUrl":"https://doi.org/10.31083/JIN53774","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of mortality and long-term disability worldwide, with complex pathophysiological mechanisms and limited therapeutic options. The identification of key molecular targets that can effectively modulate the multifaceted pathological and reparative processes underlying ischemic stroke is urgently needed. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor widely expressed in the central nervous system (CNS), where it regulates lipid and bioenergetic metabolism, preserves blood‒brain barrier (BBB) function, modulates synaptic signaling, and supports neural stem/progenitor cell homeostasis. During cerebral ischemia, LRP1 undergoes a stage-dependent functional shift. In the acute phase, LRP1 promotes BBB disruption, tissue-type plasminogen activator (tPA)-associated hemorrhagic transformation, and early neuroinflammation, while also conferring neuroprotection by restraining inflammasome-mediated inflammatory responses and facilitating astrocyte-to-neuron mitochondrial transfer. In the recovery phase, LRP1 is involved in white matter injury and remodeling, including demyelination, remyelination, and white matter restoration. These effects are highly cell type-specific, reflecting distinct functions of LRP1 in endothelial cells, astrocytes, microglia, neutrophils, and oligodendrocyte-lineage cells. This context-dependent complexity underscores the need for a systematic review of the role of LRP1 in stroke. Here, we summarize the structural features and physiological functions of LRP1 in the CNS, discuss its roles and underlying mechanisms in ischemic stroke, and highlight the therapeutic potential and challenges of LRP1-targeted strategies for stroke intervention.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"53774"},"PeriodicalIF":3.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081203","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":"Passive Behavioral Patterns in Symptomatic WAG/Rij Rats: Dissociation From Absence Epilepsy and Sex-Dependent Link Between Early Fear Coping and Post-Stress Freezing.","authors":"Evgenia Sitnikova, Maria Pupikina, Aliya Vinarskaya, Anton Kiselev","doi":"10.31083/JIN52427","DOIUrl":"https://doi.org/10.31083/JIN52427","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute stress exposure can lead to delayed behavioral changes, which are widely regarded as core endophenotypes of post-traumatic stress disorder (PTSD). Identifying pre-existing behavioral traits that predict later maladaptive responses is crucial. We investigated whether early fear-related passive coping behavior during an active avoidance task predicts subsequent freezing reactions in a safe, stimulus-free environment. This context-inappropriate fear pattern may model individual vulnerability to PTSD-like symptoms. We used Wistar Albino rats from Rijswijk (WAG/Rij rats), which are genetically predisposed to develop absence epilepsy. This condition is non-convulsive and characterized by sudden, brief periods of behavioral arrest known as absences. Absence-like seizures in WAG/Rij rats are accompanied by spike-and-wave discharge (SWDs) on electroencephalogram (EEG) and behavioral arrest. We also examined the relationship between the severity of absence epilepsy and passive behavioral patterns in WAG/Rij rats at symptomatic ages (10-12 months), as well as sex-related differences.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used an automated fear-conditioning paradigm to identify individual differences in baseline stress vulnerability that predict delayed, context-independent freezing behavior. Rats were tested in an active avoidance paradigm to assess fear-induced passive behavior under threat at the age of 9 months, and the percentage of passive behavioral responses was scored. Rats were then tested in a safe environment using the StartFear system, and the percentage of freezing was measured monthly at the ages of 10, 11, and 12 months. Finally, the rats underwent EEG examination, and SWDs were scored during 12-hour dark-phase recordings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the safe environment, 10- to 12-month-old WAG/Rij rats exhibited low levels of freezing (9.5%-13.9% of the total time). No significant sex differences were observed in freezing behavior within the safe environment. However, in the unsafe, fear-inducing active avoidance task, males displayed significantly higher levels of passive behavior than females. Female rats showed strong correlations between passive responses in the fear-inducing situation and freezing in the safe environment, whereas males did not. Results from EEG examinations indicated that males exhibited a higher number of SWDs than females. Neither the percentage of freezing in the safe environment nor the percentage of passive responses in the active avoidance task correlated with the severity of absence epilepsy, as assessed by the number and duration of SWDs. WAG/Rij rats tested after avoidance training exhibited low freezing in the StartFear paradigm and a sex-dependent increase in passive responses following conditioning; these findings are consistent with altered tonic inhibitory regulation but require naïve controls and EEG-behavior coupling to establish causality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclus","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52427"},"PeriodicalIF":3.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081216","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":"Crossing the Bar of 'Self'-A Hypothesis-Generating Value-Based Framework for Dementia Risk and Resilience.","authors":"Souvik Dubey, Mahua Jana Dubey, Samya Sengupta, Shambaditya Das, Ritwik Ghosh, Subhankar Chatterjee, Julián Benito-León","doi":"10.31083/JIN52204","DOIUrl":"10.31083/JIN52204","url":null,"abstract":"<p><p>Contemporary neuroscience increasingly conceptualizes the self as a dynamic neurocognitive process supported by interacting cortical hubs and large-scale networks. In this Opinion, we introduce self-configuration as a provisional, hypothesis-generating construct: a time-bounded, context-sensitive pattern across self-referential appraisal, interoceptive monitoring, autobiographical framing, and self-other orientation. It is not a validated scale, diagnosis, or neural biomarker and must be distinguished empirically from established constructs such as trait neuroticism, rumination, depressive symptoms, and self-transcendence. We use a heuristic continuum between a rigid, self-focused pole and a flexible, prosocial pole. Evidence supports the component psychological processes and network functions, but no study has directly linked the integrated construct to dementia risk or resilience. Accordingly, regional mappings, disease-specific emphases, and candidate manipulations are presented as falsifiable hypotheses rather than mechanisms or clinical recommendations. The framework is intended to guide multimethod construct validation and longitudinal or experimental testing, not to represent an evidence-based model of dementia risk or prevention.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52204"},"PeriodicalIF":3.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081065","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":"Askisi-MD: Development and Validation of a Web-Based Neuropsychological Screener for Mathematical Learning Difficulties Using Explainable Machine Learning.","authors":"Nikolaos C Zygouris, Stefanos K Styliaras, Filippos Vlachos, Evaggelos Spyrou, Panayiotis Patrikelis, Lambros Messinis, Grigorios Nasios","doi":"10.31083/JIN52375","DOIUrl":"https://doi.org/10.31083/JIN52375","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mathematical learning difficulties (MLD) are associated with weaknesses in both domain-specific numerical abilities and domain-general neurocognitive processes. In this study, we developed and validated a web-based neuropsychological screener, Askisi-Mathematical Difficulties (MD), that integrates cognitive control and mathematics-related tasks for the first-line identification of children at risk for MLD was developed and validated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We enrolled 564 children, including 282 children with an established MLD diagnosis recruited from a state diagnostic center and 282 typically developing children pair-matched for age and gender. Askisi-MD consisted of six tasks, including three cognitive tasks assessing inhibitory control, visual pattern recognition, and visual working memory, as well as three mathematics-related tasks assessing mental calculation verification, mathematical terminology comprehension, and arithmetic word problem operation selection. Accuracy scores and latency indicators were analyzed. Differences among groups were examined using Welch's independent-samples &lt;i&gt;t&lt;/i&gt;-tests, Benjamini-Hochberg False Discovery Rate (FDR) correction, and Hedges' g effect sizes. Internal coherence was examined using McDonald's Ω. Discriminant validity was evaluated via receiver operating characteristic (ROC) analysis and through the use of classification indices. Supervised machine learning models, including Support Vector Classifier, Random Forest, and eXtreme Gradient Boosting (XGBoost) classifiers, were trained and cross-validated, while model interpretability was examined via SHapley Additive exPlanations (SHAP) analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Children with MLD showed significantly poorer performance across all six task-score indicators after FDR correction, with moderate-to-large effect sizes. Minute-based task-completion time differences were more selective. Children with MLD showed significantly longer completion times on the Mental Calculation and Arithmetic Word Problem tasks, whereas completion-time differences were not significant for Visual Pattern Recognition Abilities or Mathematical Terminology Comprehension. McDonald's Ω indicated modest internal coherence for the neuropsychological task-score composite and the total task-score composite. The strongest internal coherence was observed for the mathematical processing-efficiency composite. ROC analysis supported strong case-control discrimination, and classification indices indicated balanced group classification. Across the cross-validation folds, XGBoost achieved the highest mean accuracy, precision, and F1 score, while XGBoost and Random Forest demonstrated the same mean recall. XGBoost also showed strong discriminative performance, as indicated by the cross-validated area under the receiver operating characteristic curve (ROC-AUC). SHAP analysis indicated that Arithmetic Word-Problem Task Latency, Arithmetic Word Pro","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52375"},"PeriodicalIF":3.3,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081095","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":"Controlling the Triple Network Model: Salience Network Modulatory Roles, Default Mode Dynamic Functions, and Central Executive Network Heterogeneity.","authors":"Martin Pham, Sonia Odutola, Hrishikesh Pable, Robin Chhabra, Amedeo D'Angiulli","doi":"10.31083/JIN52511","DOIUrl":"https://doi.org/10.31083/JIN52511","url":null,"abstract":"<p><p>The triple network model has become a widely adopted framework for studying large-scale brain organization in basic and clinical neuroscience; however, accumulating evidence complicates this taxonomy. The default mode network, once labelled \"task-negative\", is now recognized as dynamically engaged across both internally directed and task-related processes. The salience network, often described as a \"switching\" hub, exerts context-dependent modulatory influences on both default mode and central executive network activity, supported by oscillatory coupling and directed connectivity. The central executive and frontoparietal networks, traditionally viewed as a unitary task-positive network, display heterogeneity across parcellations and frequency bands, suggesting finer-grained functional subdivisions than previously assumed. Multimodal studies integrating electroencephalography, functional magnetic resonance imaging, and other approaches converge on the view that networks interact through flexible, frequency-specific dynamics, but diverge in their anatomical assignments depending on atlas, modality, and task. In this scoping review synthesizes evidence on network definitions, methodological inconsistencies, and putative modulatory mechanisms, highlighting the heterogeneity of control networks and underscoring the need to incorporate temporal dynamics into future taxonomies. We propose that geometric hypotheses of neural control describing the global coordination of local activities, such as those used in neural manifolds, may improve our understanding of disordered cognition by integrating the many existing methodologically constrained maps into a coherent stable atlas that is more robust to approximating biases and errors associated with sampled population variability.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"52511"},"PeriodicalIF":3.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891896","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":"Evaluating a Transparent Cranial Window for <i>In Vivo</i> Observation of µECoG Arrays on the Macaque Visual Cortex.","authors":"Xinwei Wang, Xiangsheng Zeng, Chengpeng Li, Danling Hu, Hisashi Tanigawa","doi":"10.31083/JIN52601","DOIUrl":"https://doi.org/10.31083/JIN52601","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;High-density micro-electrocorticography (µECoG) provides the spatiotemporal resolution necessary to probe columnar-level cortical architecture. However, chronic multimodal interfacing is fundamentally challenged by aggressive post-surgical tissue responses that rapidly obscure optical access, in addition to localization uncertainties due to brain shift. In this study, established a transparent cranial window interface on the macaque visual cortex. To evaluate the feasibility of this approach, we primarily focused on assessing strategies to mitigate dural tissue regrowth and documenting the inherent biological complications (e.g., hemorrhage), while exploring the potential for direct, &lt;i&gt;in vivo&lt;/i&gt; visual localization of µECoG arrays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A custom transparent chamber assembly integrated with a 64-channel µECoG array was implanted in the visual cortex of two rhesus macaques (&lt;i&gt;n&lt;/i&gt; = 2). We compared two dural interface designs-a floating Tecoflex sheet versus a bonded silicone ring-to optimize optical clarity and interface stability. Physical stability of the electrodes relative to vascular landmarks was quantified. Electrophysiological performance was longitudinally evaluated using impedance monitoring, visual evoked potentials, and support vector machine (SVM) neural decoding to discriminate between red-green and black-white grating stimuli, with statistical significance assessed via bootstrap tests.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Regarding the biological and electrical interfaces, while long-term optical maintenance proved challenging due to tissue regrowth or hemorrhage, the bonded silicone ring design effectively mitigated peripheral tissue invasion. Electrophysiologically, array performance captured the dynamic biological transitions of the interface. Stable impedance profiles and statistically significant gamma-band (30-80 Hz) responses-modulating from initial widespread coverage (up to 100%) to restricted subsets (e.g., 16% at five months)-alongside robust SVM classification accuracy (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) were tracked longitudinally. Additionally, as a preliminary observation in a single subject, the transparent window permitted the precise identification of electrode positions relative to cortical vasculature, revealing minor physical displacements (median = 0.20 mm) within the initial two weeks post-implantation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Comparing two dural interface designs highlights the mechanical and biological trade-offs required for chronic optical access, emphasizing that optimizing the mechanical compliance of the dural seal is a critical consideration for long-term multimodal interfaces. Furthermore, this interface shows the potential to overcome conventional localization limitations through early-stage visual co-registration. Although maintaining permanent optical clarity remains a fundamental challenge due to aggressive tissue responses, the system supports","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"52601"},"PeriodicalIF":3.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891923","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":"Shikonin Attenuates Neuroinflammation and Depression-Like Behaviors by Regulating Microglial Polarization Through Inhibiting cGAS-STING/NF-κB Signaling and Lipid Droplet Accumulation.","authors":"Zi Chai, Wen-Ting Liu, Han-Yang Liu, Yuan-Yuan Su, Su-Yuan Ma, Hong-Tao Liang, Ya-Qin Li, Rui Liu","doi":"10.31083/JIN50217","DOIUrl":"https://doi.org/10.31083/JIN50217","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder is a disabling psychiatric illness with a growing global burden. Neuroinflammation, particularly microglial polarization, is increasingly recognized as a key pathogenic factor and is closely linked to lipid metabolic regulation. Shikonin, a bioactive naphthoquinone from <i>Lithospermum erythrorhizon</i>, exhibits anti-inflammatory and antioxidant properties, yet its antidepressant effects remain unclear. This study examined whether shikonin alleviates depressive-like behaviors by suppressing neuroinflammation.</p><p><strong>Methods: </strong>Mice were orally treated with shikonin for two weeks before the induction of learned helplessness (LH). A series of behavioral paradigms tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT), and escapable shocks test (EST) was employed to evaluate depression-related behaviors. Following behavioral testing, inflammatory mediators, activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, microglial lipid droplet accumulation, autophagic status, and M1/M2 polarization markers were evaluated. <i>In vitro</i>, mouse microglial cell line BV2 (BV2) microglia were activated by lipopolysaccharide (LPS). A cell counting kit-8 (CCK-8) assay was conducted to screen non-cytotoxic shikonin concentrations, with subsequent <i>in vitro</i> verification of <i>in vivo</i> outcomes. The role of lipophagy in microglial polarization was further examined through pharmacological modulation of autophagy using chloroquine and rapamycin.</p><p><strong>Results: </strong>Shikonin markedly alleviated depression-like behaviors in LH mice, accompanied by decreased interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression and inhibition of the cGAS-STING pathway. Mechanistically, shikonin suppressed M1 microglial polarization and lipid droplet accumulation in the hippocampus by restoring autophagic flux. Shikonin exerted anti-inflammatory effects <i>in vitro</i> by inhibiting cGAS-STING-dependent M1 polarization and restoring lipophagy in LPS-stimulated BV2 cells.</p><p><strong>Conclusions: </strong>Our findings show that shikonin suppresses cGAS-STING activation, shifts microglia away from the M1 phenotype, and promotes autophagy, thereby reducing lipid droplet accumulation and alleviating neuroinflammation and depressive-like symptoms.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 8","pages":"50217"},"PeriodicalIF":3.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891855","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}