Journal of integrative neuroscience最新文献

{"title":"Zebrafish as an Alternative Animal Model of Huntington's Disease: Challenges and Future Directions.","authors":"Jiahao Cui, Zhili Yu, Zhike Fu, Vera Pushkina, Ekaterina Kozlova, Yixuan Pang, Yimeng Wang, Yubo Xiao, Murilo S de Abreu, Longen Yang, Valentina N Perfilova, Adam Michael Stewart, Allan V Kalueff","doi":"10.31083/JIN49403","DOIUrl":"https://doi.org/10.31083/JIN49403","url":null,"abstract":"<p><p>Huntington's disease (HD) is a lethal autosomal dominant neurodegenerative disorder characterized by progressing cognitive, motor, and other behavioral deficits. Animal models, especially rodent-based, are a valuable tool to study brain disorders, including HD. Given the existence of multiple valid and predictive models of HD and other brain disorders, we are now entering a phase of mechanistic discovery, as research shifts towards phenotype-based screening and multi-omic validation. In addition to rodent models, zebrafish (<i>Danio rerio</i>) are rapidly becoming a promising model organism for translational HD research. With considerable genetic homology to humans, embryonic transparency for real-time pathology tracking, physiological similarity to mammals, and high-throughput drug screening potential, zebrafish have become a valuable alternative model organism in translational HD research. Here, we discuss zebrafish HD models, their advantages and limitations, and future directions of translational research in this field.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"49403"},"PeriodicalIF":3.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081027","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":"Unlocking Early Neural Plasticity: A Systematic Review and Meta-Analysis of Repetitive Transcranial Magnetic Stimulation on Motor Recovery in Acute Stroke.","authors":"Meixi Liu, Haozheng Li, Guohui Yang, Xiaoman Deng, Chong Guan, Xiuqin Lv, Shucong Peng, Junqiu Ma, Xiangtong Ji, Yi Wu, Lu Luo","doi":"10.31083/JIN49076","DOIUrl":"10.31083/JIN49076","url":null,"abstract":"<p><strong>Background: </strong>Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy as a neuromodulatory technique in subacute and chronic stroke phases. However, evidence regarding its effectiveness in the acute phase remains limited, necessitating further synthesis and evaluation.</p><p><strong>Methods: </strong>A comprehensive search was conducted across PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL (EBSCOhost) to November 1, 2025. The intervention in the experimental group must involve rTMS with or without any additional rehabilitation. Using a random-effects model, standardized mean differences (Hedges' g) were calculated for motor function (Fugl-Meyer Assessment, FMA), neurological deficits (National Institutes of Health Stroke Scale, NIHSS), independence (Barthel Index, BI), disability (Modified Rankin Scale, mRS), grip strength, and neurophysiological parameters (Motor Evoked Potential (MEP) amplitude, resting motor threshold (RMT), Central Motor Conduction Time (CMCT)). Heterogeneity was assessed using the <i>I²</i> statistic, and analyses were conducted with Stata.</p><p><strong>Results: </strong>A systematic literature search identified 17 studies meeting the inclusion criteria involving 846 acute ischemic stroke adults. rTMS significantly improved motor recovery (FMA: <i>p</i> < 0.01) and reduced neurological deficits (NIHSS: <i>p</i> < 0.01). It also enhanced independence (BI: <i>p</i> = 0.01) and reduced disability (mRS: <i>p</i> < 0.01; grip strength: <i>p</i> = 0.01). Neurophysiological outcomes indicated increased corticospinal excitability in the lesioned hemisphere (MEP amplitude: <i>p</i> < 0.01) and reduced RMT (<i>p</i> < 0.01), with no significant effect on CMCT. Subgroup analyses showed comparable benefits between ipsilesional high-frequency and contralesional low-frequency rTMS, though high-frequency protocols yielded significant improvements in activities of daily living (<i>p</i> = 0.01). Subthreshold stimulation and threshold stimulation were associated with NIHSS improvements (<i>p</i> < 0.01). Suprathreshold stimulation showed a non‑significant effect (<i>p</i> = 0.11).</p><p><strong>Conclusions: </strong>Despite heterogeneity and limitations in evidence quality, rTMS shows promise as a neurorehabilitative intervention in acute stroke, potentially by modulating interhemispheric balance and promoting neuroplasticity.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"49076"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080615","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":"SPATA2 Attenuates Inflammatory Injury Through CYLD-Related Regulation of Microglial Inflammatory Responses After Focal Cerebral Ischemia/Reperfusion in Rats.","authors":"Jin Jiang, Xingrui Li, Yexiang Du, Yehong Du, Wei Yu","doi":"10.31083/JIN51769","DOIUrl":"https://doi.org/10.31083/JIN51769","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Post-ischemic inflammation is strongly influenced by interactions between neurons and microglia. We previously observed that spermatogenesis-associated protein 2 (SPATA2) alleviates inflammatory injury following cerebral ischemia/reperfusion; however, the relationship between SPATA2, cylindromatosis (CYLD)-associated inflammatory signaling, and microglial inflammatory responses remains incompletely understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adult Sprague-Dawley (SD) rats were subjected to transient middle cerebral artery occlusion followed by reperfusion. SPATA2 expression was knocked down &lt;i&gt;in vivo&lt;/i&gt; via intracerebroventricular lentiviral delivery. Neurological function and infarct volume were evaluated after reperfusion. Selected pro-inflammatory and anti-inflammatory/reparative markers were assessed by immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). Double immunofluorescence staining of SPATA2 with neuronal nuclei (NeuN), ionized calcium-binding adapter molecule 1 (Iba1), or glial fibrillary acidic protein (GFAP) was performed to examine the cellular localization of SPATA2 in the peri-ischemic cortex. To further assess neuron-to-microglia regulation, primary neurons and microglia were cultured in a Transwell system and exposed to oxygen-glucose deprivation/reperfusion. SPATA2 knockdown and overexpression, together with CYLD knockdown in SPATA2-overexpressing cells, were used to investigate CYLD-associated signaling. Co-immunoprecipitation (Co-IP) was performed to assess CYLD-heme-oxidized IRP2 ubiquitin ligase 1L-like interacting protein (HOIP) association.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SPATA2 knockdown exacerbated neurological deficits and increased infarct volume following middle cerebral artery occlusion (MCAO). In peri-ischemic cortex tissue, SPATA2 knockdown increased the proportion of Iba1+/cluster of differentiation 86 (CD86)+ cells while reducing the proportion of Iba1+/CD206+ cells. Representative double-immunofluorescence images showed that SPATA2 immunoreactivity predominantly overlapped with NeuN-positive neurons, with relatively limited overlap with Iba1-positive microglia or GFAP-positive astrocytes. In the Transwell-based neuron-microglia system, depletion of SPATA2 in neurons shifted microglia toward a stronger inflammatory profile, as reflected by elevated secretion of interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and soluble C-X-C motif 3 chemokine ligand 1 (CX3CL1). By contrast, neuronal SPATA2 overexpression attenuated these inflammatory changes. At the mechanistic level, SPATA2 overexpression strengthened the association between CYLD and HOIP, together with reduced nuclear factor-κB (NF-κB) p65 expression and decreased soluble CX3CL1 release. When CYLD was silenced, the suppressive influence of SPATA2 overexpression on NF-κB p65 expression and soluble CX3CL1 release was partly weaken","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"51769"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081230","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":"The Role of SPTLC2 and the MEK/ERK Signaling Pathway in the Metabolic Activity and Proliferation of Neural Stem Cells.","authors":"Tianqing Liu, Bo Li, Folin Lan, Junlong Huang, Yuqin Ye, Xinhong Su","doi":"10.31083/JIN52923","DOIUrl":"https://doi.org/10.31083/JIN52923","url":null,"abstract":"<p><strong>Background: </strong>The use of neural stem cells (NSCs) to facilitate neurogenesis and improve impaired neural functions has attracted significant attention. Serine palmitoyltransferase long chain base subunit 2 (SPTLC2) induces apoptosis of neurons, while the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway promotes NSC differentiation and proliferation. This study investigated the roles of SPTLC2 and the MEK/ERK pathway on the proliferation and metabolic activity of NSCs.</p><p><strong>Methods: </strong>SPTLC2 expression was altered through plasmid transfection and verified by Western blot and polymerase chain reaction (PCR) analyses. The effects of altered SPTLC2 expression on the metabolic activity and proliferation of NSCs were subsequently assessed using a cell counting kit and staining with 5-ethynyl-2'-deoxyuridine (EdU). Western blotting was used to examine the relationship between SPTLC2 and the MEK/ERK pathway by investigating changes in protein expression. To determine whether SPTLC2 acts via the MEK/ERK pathway, the activation state of this pathway was manipulated with U0126 and Erucin. Western blot and EdU staining were used to assess whether SPTLC2 affected the proliferation and metabolic activity of NSCs via the MEK/ERK pathway.</p><p><strong>Results: </strong>Plasmid transfection led to significant changes in SPTLC2 expression at both the mRNA (<i>p</i> < 0.01) and protein (<i>p</i> < 0.05) levels. SPTLC2 overexpression significantly reduced the proliferation and metabolic activity of NSCs (<i>p</i> < 0.05), whereas SPTLC2 knockdown mediated by siRNA significantly enhanced both parameters (<i>p</i> < 0.05). Western blot analysis revealed that the ratios of p-MEK/MEK and p-ERK/ERK were inversely correlated with the expression level of SPTLC2 (<i>p</i> < 0.05). Pharmacological modulation of the MEK/ERK pathway significantly reversed the SPTLC2-induced changes in pathway activity (<i>p</i> < 0.05) and partially restored the associated proliferative phenotypes.</p><p><strong>Conclusions: </strong>These findings indicate that SPTLC2 overexpression inhibits the proliferation and metabolic activity of NSCs, and that downregulation of SPTLC2 promotes these processes. The effects of SPTLC2 on NSCs were functionally associated with the MEK/ERK pathway.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52923"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081147","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":"Longitudinal Changes in Hippocampal-Default Mode Network Connectivity and Cognition During Electroacupuncture Intervention in Type 2 Diabetes-Associated Cognitive Decline: A Pilot Resting-State fMRI Study.","authors":"Lin Yao, Meng-Yuan Li, Yan-Ze Liu, Jia-Zhen Cao, Zheng Lian, Hong-Nan Zhu, Hai-Peng Huang, Zhen Zhong, Hong-Feng Wang","doi":"10.31083/JIN52929","DOIUrl":"10.31083/JIN52929","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) is strongly linked to disruption of cognition-supporting brain networks. Electroacupuncture (EA) has increasingly been examined as a nonpharmacological intervention targeting cognitive impairment; however, the longitudinal neurobiological patterns accompanying EA in T2DACD have not been fully characterized. In this exploratory pilot study, we evaluated alterations in resting-state functional connectivity (RSFC) across hippocampal subregions and default mode network (DMN) nodes in individuals with T2DACD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;For this exploratory, open-label, non-randomized, uncontrolled pilot investigation, we enrolled 20 individuals with T2DACD and 26 healthy controls (HCs). Longitudinal analyses included 15 participants who had usable post-treatment data. T2DACD was defined according to clinical type 2 diabetes mellitus criteria, and a Montreal Cognitive Assessment (MoCA) score &lt;26. Patients underwent an 8-week Adjust Zang-fu and Arouse Spirit electroacupuncture (AZASE) intervention. Cognitive, emotional, metabolic, and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) outcomes were evaluated. Clinical longitudinal analyses were carried out according to protocol, whereas imaging analyses were limited to participants with usable scans after treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At baseline, individuals with T2DACD showed lower MoCA scores than HCs and had poorer executive and working-memory outcomes. Among the 15 participants with complete longitudinal neuroimaging data, MoCA scores increased from 23.27 ± 1.71 to 26.07 ± 1.53 over the intervention period. Within-group alterations were observed for Flanker-conflict reaction time and accuracy, Stroop-conflict reaction time, 1-back reaction time, Self-Rating Anxiety Scale score, and Hamilton Depression Rating Scale score. Omnibus group analyses detected significant effects for the left anterior hippocampus-left angular gyrus connection and the left posterior hippocampus-right middle occipital gyrus connection. Post-treatment scans demonstrated reduced RSFC in several hippocampal-DMN and intra-DMN connections. The association between change in left anterior hippocampus-left angular gyrus RSFC and change in Stroop-conflict performance was no longer statistically significant after Bonferroni correction. For neuroimaging outcomes, cluster-level family-wise error (FWE) correction (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) was applied to control for multiple comparisons; clinical outcomes are reported descriptively as hypothesis-generating findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this exploratory pilot study, we identified preliminary alterations in cognitive outcomes and hippocampal-DMN connections over an 8-week EA intervention in individuals with T2DACD. In view of the small sample size and the open-label, non-randomized, uncontrolled design, the findings should be interpreted as hy","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52929"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081160","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":"Esketamine Ameliorates Propofol-Induced Long-Term Cognitive Impairments in Juvenile Rats by Suppressing Autophagy via Activating the PI3K/Akt/mTOR Signaling Pathway.","authors":"Yang Wang, Yin Li, Zhe Chen, Xuexue Zhang, Na Qi, Xueying Chen, Guiping Xu","doi":"10.31083/JIN50741","DOIUrl":"https://doi.org/10.31083/JIN50741","url":null,"abstract":"<p><strong>Background: </strong>Repeated propofol exposure during neurodevelopment induces long-term cognitive deficits in rats, potentially through dysregulated hippocampal neuronal autophagy and inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway. Esketamine has been reported to exert neuroprotective effects; however, the underlying mechanism remains unclear. In the present study, we investigated whether esketamine could ameliorate propofol-induced long-term memory and learning impairments in juvenile rats by suppressing autophagy via activation of the PI3K/Akt/mTOR pathway.</p><p><strong>Methods: </strong>Seventy-two Sprague-Dawley rats of both sexes at postnatal day 7 were randomly assigned to one of six groups: Control, Propofol, Esketamine + Propofol, LY294002 (PI3K inhibitor) + Esketamine + Propofol, Rapamycin + Propofol, and Rapamycin + Esketamine + Propofol. All treatments were administered daily for five consecutive days. Cognitive performance was assessed using both the Y-maze test and the Morris water maze test. Hippocampal neuronal pathology was evaluated by histopathological staining and transmission electron microscopy. The concentrations of pro-inflammatory cytokines and expression levels of proteins related to the PI3K/Akt/mTOR pathway and autophagy were measured using Western blotting and immunofluorescence.</p><p><strong>Results: </strong>Rats exposed to propofol showed significant learning and memory impairments, hippocampal neuronal damage, suppression of the PI3K/Akt/mTOR pathway, excessive autophagy, and elevated levels of pro-inflammatory cytokines (<i>p</i> < 0.01). Esketamine co-treatment significantly alleviated these propofol-induced changes (<i>p</i> < 0.01). However, the neuroprotective effects of esketamine were diminished by pre-treatment with either LY294002 or the autophagy activator rapamycin (<i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>Esketamine ameliorates propofol-induced long-term cognitive impairments in juvenile rats by suppressing excessive autophagy through activation of the PI3K/Akt/mTOR signaling pathway.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"50741"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081122","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":"Resting-EEG Characteristics and Classification Model Exploration for Tap Test Prediction in Communicating Hydrocephalus: A Small-Sample Pilot Study.","authors":"Nan Bai, Zijia Guo, Wenxuan Xin, Maosheng Xiang, Junhao Zhu, Yuanming Geng, Weiyi Xie, Chiyuan Ma","doi":"10.31083/JIN53811","DOIUrl":"https://doi.org/10.31083/JIN53811","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Communicating hydrocephalus is characterized by gait disturbance, cognitive impairment, and altered consciousness. The cerebrospinal fluid (CSF) tap test is widely used to predict shunt responsiveness; however, objective neurophysiological markers are still lacking. Resting-state electroencephalography (RS-EEG) may offer insights into brain network function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Thirty patients with communicating hydrocephalus underwent 19‑channel RS‑EEG before the CSF tap test. Multimodal EEG features were extracted from 2‑second epochs, including spectral power, functional connectivity (coherence and phase‑locking value), and nonlinear measures (approximate entropy, Hjorth parameters), then aggregated to subject‑level representations. Group differences were explored via correlation with clinical scales, source‑level phase transfer entropy, and t-distributed Stochastic Neighbor Embedding (t‑SNE) visualization. For classification, logistic regression, linear support vector machine (SVM), and a deep neural network (fully connected or 1D Convolutional Neural Network [1D‑CNN]) were trained and compared under nested leave‑one‑subject‑out cross‑validation with within‑fold feature selection. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), permutation tests, bootstrap 95% confidence intervals, and DeLong tests.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Responders showed higher alpha-band power, which correlated with Coma Recovery Scale-Revised (CRS-R) improvement (r = -0.764, &lt;i&gt;p&lt;/i&gt; = 0.0004) but not Mini-Mental State Examination (MMSE). Functional connectivity and source-level analyses showed descriptive trends that did not survive false discovery rate correction. t-SNE visualization showed partial separation of responders and non-responders, and EEG data quality did not differ between groups. For classification, linear models matched or exceeded deep learning: in the disorders of consciousness (DOC) subgroup, logistic regression (LR) and SVM achieved an AUC of 0.982 (95% CI: 0.909-1.000) & 0.982 (95% CI: 0.893-1.000) vs. 0.964 (0.84-1.00) for the fully connected network; in the cognitive subgroup, SVM reached an AUC of 0.963 (0.84-1.00), followed by CNN (0.944) and LR (0.926). All models were significant by permutation test (&lt;i&gt;p&lt;/i&gt; &lt; 0.002). DeLong tests showed no significant difference between deep learning and the best linear model (&lt;i&gt;p&lt;/i&gt; &gt; 0.4), indicating that EEG features are largely linearly separable. Bootstrap confidence intervals remained above 0.73.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These findings indicate that EEG-derived spectral features, particularly alpha and theta power, contain linearly separable information related to tap test responsiveness. Linear machine learning models performed on par with deep learning, underscoring the robustness of the neural signal and cautioning against unnecessary model complexity in small clinical samples. This","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"53811"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081200","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":"Inter-Postsynaptic Functional Links for Associative Memory: Feasibility in a Realistic Neuropil Model.","authors":"Kunjumon I Vadakkan","doi":"10.31083/JIN49226","DOIUrl":"https://doi.org/10.31083/JIN49226","url":null,"abstract":"<p><strong>Aim: </strong>To quantify neuronal input degeneracy and test computationally whether nanoscale (≤30 nm) spine appositions are structurally eligible sites for inter-postsynaptic functional links (IPLs) underlying associative learning, assuming plausible pathway convergence onto abutted spine pairs. Empirical Constraint: Neuronal firing exhibits extreme input degeneracy. Any subset of inputs arriving at ~100-200 out of ~10⁴ spines can trigger an action potential; ~140 inputs yield >10³⁰⁰ possible effective input combinations. This degeneracy introduces ambiguity regarding the specific input combinations that contribute to associative encoding. Testable Mechanism: The semblance hypothesis proposes a spine-level conjunction code between co-active spines forming inter-postsynaptic functional links (IPLs) that operate independently of postsynaptic neuronal firing, and are proposed to maintain the fidelity of original associations during retrieval. Computational Validation: During retrieval, cue-induced reactivation of IPLs is hypothesized to depolarize inter-linked spines and generate semblances. Taking the depolarization of an inter-linked spine in the absence of direct presynaptic input as an \"operational semblance\" constituting the elemental substrate of associative recall, a computational model was implemented within a biologically realistic 1000 μm³ neuropil volume containing 1600 dendritic spines (density 1.6/μm³; diameter 0.6-0.7 μm) as independent dendritic segments. Of 391 crossing dendritic sites, 151 have abutted spine pairs, using ≤30 nm inter-spine distance as a candidate eligibility criterion, motivated by reported nanoscale appositions. Spine density, diameter, and separation were parameterized from electron microscopy and confocal/super-resolution imaging literature; coupling strength (0.7) was fixed and exploratory. IPL formation was implemented probabilistically across 20 learning trials (formation probability = 0.30 per trial at each of the 49 designated sites; reversal probability = 0.04), producing a gradual acquisition curve and trial-to-trial variance emerging naturally from the two-state Markov dynamics. Across 100 independent simulations, 49 of the 151 abutted pairs were designated as structurally eligible Bell-Food convergence sites; of these, 44.7 ± 2.1 developed active IPLs after 20 trials, generating operational semblances per retrieval (recall accuracy 36.93% ± 1.71%; paired <i>t</i>-test, <i>p</i> < 0.001; Cohen's d = 30.54, illustrative not calibrated). This work demonstrates that given a plausible convergence of associative pathways onto existing abutted spine pairs, the structural relations between spines in the cortical neuropil are compatible with the formation of a spine-level conjunction code as a potential substrate for associative learning.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"49226"},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081114","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":"Mechanistic Study on HSP90B1 Regulation of ClC-7 Ubiquitination to Restore Lysosomal Function in the Protection Proffered by DGMI Against Fluoride-Induced Cognitive Dysfunction.","authors":"Rui Chen, Peng Xie, Xinrui Fan, Zihang Zhou, Chunyan Mu, Qiuhong Ji","doi":"10.31083/JIN53296","DOIUrl":"https://doi.org/10.31083/JIN53296","url":null,"abstract":"<p><strong>Background: </strong>Fluorosis can induce cognitive dysfunction. The cognitive impairment caused by fluorosis is closely related to endoplasmic reticulum stress (ERS) and abnormal lysosomal acidification. However, the specific molecular mechanism is not known, and effective intervention strategies are lacking. Diterpene ginkgolides meglumine injection (DGMI) is used clinically as a neuroprotective agent, but whether it can inhibit ERS, regulate lysosomal acidification, and ameliorate fluorosis-induced cognitive dysfunction merits investigation.</p><p><strong>Methods: </strong>We used the Morris water maze to detect the cognitive function of mice, evaluated the neuronal survival by Nissl staining, assessed the apoptotic status in hippocampal neurons of mice by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and observed the degree of synaptic plasticity damage using Golgi staining and transmission electron microscopy. In cell experiments, we used the OG488 acidophilic fluorescent probe to detect lysosomal acidity; detected the co-localization of HSP90B1 with the ER and the co-localization of the chloride channel, voltage-sensitive 7 (ClC-7) with lysosomes using immunofluorescence technology; employed co-immunoprecipitation to detect the binding of HSP90B1, ClC-7, and membrane-associated RING-CH protein 1 (MARCHF1) as well as the ubiquitination degradation level of ClC-7; used western blotting to measure expression of ERS-related proteins (PERK, IRE1α, ATF6), glycogen synthase kinase 3β, and mammalian target of rapamycin signals.</p><p><strong>Results: </strong>DGMI significantly improved cognitive dysfunction in C57BL/6 mice with fluorosis, inhibited hippocampal neuronal apoptosis, and improved synaptic plasticity damage. In cell experiments, the detection results of apoptosis and percent survival were consistent with those of animal experiments in that DGMI could alleviate sodium fluoride-induced ERS and lysosomal-acidification disorders in HT22 cells. DGMI downregulates the expression of the ER chaperone HSP90B1, weakens its interaction with ClC-7, thereby inhibiting the MARCHF1 E3 ligase-mediated ubiquitination and degradation of ClC-7, ultimately alleviating lysosomal acidification disorders and improving cognitive function.</p><p><strong>Conclusions: </strong>DGMI may exert cognitive protective effects against fluorosis-induced cognitive impairment by regulating lysosomal acidification through the HSP90B1-ClC-7 axis, which also alleviates ERS, apoptosis, and other related neuropathologic injuries.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"53296"},"PeriodicalIF":3.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081132","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":"Therapeutic Applications of rTMS in Migraine Prophylaxis.","authors":"Vasileios Siokas, Chrysoula Marogianni, Ioannis Liampas, Maria Sokratous, Daniil Tsirelis, Stavroula Dardioti, Antonia Tsika, Polyxeni Stamati, Efthimios Dardiotis","doi":"10.31083/JIN52992","DOIUrl":"https://doi.org/10.31083/JIN52992","url":null,"abstract":"<p><p>Migraine is one of the main causes of neurological disability, especially in young adults. Recent developments in preventive migraine therapies have improved outcomes for many patients, while highlighting the need for additional therapeutic options for those who remain refractory to pharmacological prophylaxis. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a promising neuromodulatory tool. We searched published literature for articles describing the efficacy of different rTMS protocols in the treatment of migraine. The literature search was conducted using PubMed and Scopus for articles published up to March 26, 2026. Twenty-four articles were categorized based on cortical targets (primary motor cortex [M1], dorsolateral prefrontal cortex (DLPFC), Vertex, Visual Cortex or Multifocal). High-frequency rTMS (HF-rTMS) targeting either the M1 or the left DLPFC demonstrated potential efficacy for specific goals such as reducing monthly migraine days, pain intensity, and medication intake. According to studies using neurophysiological data (obtained via transcranial magnetic stimulation-electroencephalography (TMS-EEG)), clinical improvement correlates with enhanced frontotemporal network connectivity and restored cortical plasticity. Guided rTMS stimulation through functional connectivity between the DLPFC and the pregenual cingulate cortex (PGC) may increase the precision of pain processing network modulation. Low-frequency rTMS (LF-rTMS) protocols also show potential benefits, including reductions in headache frequency, intensity, disability and medication use, although the supporting evidence is limited and derived primarily from small and uncontrolled studies. Multifocal rTMS paradigms showed promising efficacy in episodic migraine. Considerable heterogeneity in study design, stimulation protocols, and outcome measures limited the ability to draw reliable conclusions. Frequency and localization may be important determinants of clinical success. Future research should focus on network-based, personalized stimulation protocols to potentially increase long-term therapeutic benefit.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"25 9","pages":"52992"},"PeriodicalIF":3.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081154","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}