Translational Neuroscience最新文献

{"title":"The active construction of past episodes.","authors":"Thomas Parr, Giovanni Pezzulo, Karl J Friston","doi":"10.1515/tnsci-2025-0391","DOIUrl":"10.1515/tnsci-2025-0391","url":null,"abstract":"<p><p>Episodic memories - declarative memories of past events, characterized by rich spatiotemporal context - play a central role in guiding perception and behaviour. Here, we advance a model that integrates episodic memories within the active inference framework. We describe how episodic memories are incorporated into the generative models used in active inference to support the re-construction, replay and communication of past events. In doing so, we foreground two foundational themes. The first is the message passing in deep temporal models that allow one to actively construct memories of episodes. The second is the communicative aspect of declarative memories, and the way in which one might recount something from one's autobiography. In effect, this means that the message passing that supports episodic memory propagates information about what we have done - or what we would do - given past circumstances to draw inferences about how to communicate those beliefs. Together, these themes emphasise that we are not passive recorders of the things that happen to us. We are active participants in the events we recall and in the telling of stories about them.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"17 1","pages":"20250391"},"PeriodicalIF":2.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quo Vadis translational neuroscience?","authors":"Ekrem Dere","doi":"10.1515/tnsci-2025-0393","DOIUrl":"10.1515/tnsci-2025-0393","url":null,"abstract":"<p><p>Translational neuroscience is a research discipline that aims to transfer findings from basic research in neuroscience into clinical applications. The main goal of this research discipline is to gain molecular and mechanistic insight into brain diseases and to devise novel diagnostic tools and therapeutic applications. This review is organized in three major sections which address recent developments in diagnostic innovation, therapeutic translation and integrative modelling. Furthermore, the most urgent problems and challenges of translational neuroscience as a research discipline are presented and viable solutions are discussed. Promising novel methods are presented, and suggestions for new research approaches are made. Although translational neuroscience deals with diseases of the most complex human organ that there is, the brain, it is likely to turn out to be one of the few disciplines in life sciences that will continue to see steady progress and discoveries.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"17 1","pages":"20250393"},"PeriodicalIF":2.2,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study on the effects of unilateral biportal endoscopic lumbar interbody fusion on functional recovery in patients undergoing single-level lumbar interbody fusion.","authors":"Xinyun Huang, Shi Ling, Qi Cao","doi":"10.1515/tnsci-2025-0390","DOIUrl":"10.1515/tnsci-2025-0390","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the clinical outcomes of unilateral biportal endoscopic lumbar interbody fusion (ULIF) versus posterior lumbar interbody fusion (PLIF) in patients undergoing single-level L3-S1 lumbar interbody fusion.</p><p><strong>Methods: </strong>A total of 169 patients were included, with 83 patients who underwent posterior lumbar interbody fusion (PLIF) serving as the control group and 86 patients who underwent ULIF comprising the observation group. Short-term surgical outcomes, including muscle integrity, pain relief, functional recovery, and systemic inflammatory responses, were compared between the two groups.</p><p><strong>Results: </strong>Compared with PLIF, ULIF was associated with a longer operative time but less intraoperative blood loss and lower total postoperative drainage (p<0.05). At 1 and 3 months postoperatively, patients in the ULIF group had less pain and better lumbar function, as indicated by significantly lower visual analog scale (VAS) and Oswestry Disability Index (ODI) scores (p<0.05), without contradiction in long-term comparison. At the 1 year postoperatively, the ULIF group showed a higher intact multifidus muscle retention rate on the healthy side at the L3-L4, L4-L5, and L5-S1 levels (all p<0.05), suggesting a potential benefit in muscle preservation. Serum levels of adrenocorticotropic hormone (ACTH), cortisol (Cor), and tumor necrosis factor-alpha (TNF-α) increased in both groups at 1 and 3 days postoperatively; however, the increases were significantly lower in the ULIF group (p<0.05). Serum creatine kinase (CK) levels increased in both groups at 3 and 7 days postoperatively, but the increase was significantly smaller in the ULIF group, with a marked difference in CK reduction by day 7 (p<0.05).</p><p><strong>Conclusions: </strong>ULIF is a safe and effective minimally invasive surgical technique for single-level lumbar interbody fusion. Compared with PLIF, ULIF promotes early pain relief and functional recovery, and reduces perioperative physiological stress and tissue trauma.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"17 1","pages":"20250390"},"PeriodicalIF":2.2,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Two-way Mendelian randomisation study of inflammatory factors and the risk of meningioma.","authors":"Jiming Sun, Xinlei Yang, Han Gao, Rui Lin, Xiaobo Sun, Qiutao Li, Xinyu Chang, Shengxin Bao, Yu Fan, Yiran Du","doi":"10.1515/tnsci-2025-0389","DOIUrl":"10.1515/tnsci-2025-0389","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the causal relationship between inflammatory factors and meningioma.</p><p><strong>Methods: </strong>The inverse variance weighting method (IVW), Mendelian Randomisation Egger (MR-Egger) regression, weighted median method, simple mode method, and weighted mode method were used to analyse the potential causal relationship between exposure factors and outcomes.</p><p><strong>Results: </strong>Preliminary MR analysis showed that 6 inflammatory factors, including C-C motif chemokine 19 levels, osteoprotegerin levels, Fms-related tyrosine kinase 3 (FLT3) ligand levels, matrix metalloproteinase-1 levels, C-C motif chemokine 28 levels, and interleukin-5 levels, were associated with meningiomas. Further screening of inflammatory factors and positive MR analysis showed that FLT3 ligand levels had a clear causal association with the occurrence of meningioma (odds ratio [OR]=0.713, 95 % confidence interval [CI]: 0.598-0.851). The results of reverse MR analysis showed that there was a clear causal association between meningioma and Fms-related tyrosine kinase 3 ligand levels (OR=0.936, 95 % CI: 0.885-0.990). The results of heterogeneity and pleiotropic tests of MR-Egger intercept showed that there was no heterogeneity or pleiotropy in all data.</p><p><strong>Conclusions: </strong>This study clarified FLT3 as being involved in the pathogenesis of meningioma from a genetic perspective and genetically predicted lower FLT3L to be causally associated with a higher meningioma risk, implicating FLT3 signalling in meningioma pathogenesis. FLT3 as a genetically supported candidate factor associated with meningioma risk.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"17 1","pages":"20250389"},"PeriodicalIF":2.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12917583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Episodic memory in animals?","authors":"Thomas R Zentall","doi":"10.1515/tnsci-2025-0383","DOIUrl":"10.1515/tnsci-2025-0383","url":null,"abstract":"<p><p>Episodic memory refers to the recall of memories concerned with unique, personal past experiences. It has been differentiated from semantic or rule learning that may be associatively learned. Episodic memory has the quality of mentally traveling back in time to recover a memory. Episodic memory is believed to be related to language and consciousness, and for this reason, has been thought to be unique to humans. Having episodic memory generally allows one to describe what happened, where it happened, and when it happened. For some time, research has focused on these three properties, and research with animals indicates that several species do have the capacity to behaviorally report the what, where, and when of an event. But such evidence is not sufficient to conclude that animals have episodic memory. Instead, to better distinguish episodic memory from semantic or rule learning, an organism should be able to respond appropriately to an unexpected question about an event that was incidentally rather than explicitly encoded. Using this criterion, there is growing evidence that several species do have such an ability. Furthermore, it is proposed that episodic memory serves to enable future planning, and animals show some evidence for that as well.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250383"},"PeriodicalIF":2.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12658725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel dynamic nomogram based on clinical features and laboratory indicators for diagnosis of post-neurosurgery intracranial infection.","authors":"Minjie Tang, Qingwen Lin, Kengna Fan, Zeqin Zhang, Weiqing Zhang, Qi Wang, Tianbin Chen, Qishui Ou, Xiaofeng Liu","doi":"10.1515/tnsci-2025-0382","DOIUrl":"10.1515/tnsci-2025-0382","url":null,"abstract":"<p><strong>Objective: </strong>Intracranial infection is a serious complication after neurosurgery. However, the early diagnosis of post-neurosurgical intracranial infection (PNICI) remains challenging. The purpose of this study was to compare clinical characteristics and common laboratory indicators in patients with and without intracranial infections after neurosurgery and construct a diagnostic model of PNICI and assess its diagnostic efficacy.</p><p><strong>Methods: </strong>A total of 623 patients who underwent neurosurgery from January 2018 to October 2021 were enrolled and divided into a training set and a validation set. SPSS 22.0 software was used to compare the differences in basic information and laboratory examination results between the two groups to screen out valuable indicators. Subsequently, a nomogram for the diagnosis of PNICI was established. Then, the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA) were performed to evaluate the discriminative ability, consistency, and clinical usefulness of the nomogram.</p><p><strong>Results: </strong>The diagnostic model of PNICI consisted of seven variables: meningeal irritation, fever, postoperative drainage, cerebrospinal fluid (CSF) white blood cells, CSF chlorine, the CSF/blood glucose ratio, and blood neutrophil percentage. The model achieved an area under the ROC curve of 0.958 in the training set and 0.966 in the validation set. At the optimal cutoff of 0.397, the training set demonstrated 90.4% sensitivity and 90.8% specificity. The calibration curves and DCA curves of the nomogram demonstrated that the model exhibited good goodness of fit and showed a net benefit from its use.</p><p><strong>Conclusions: </strong>We developed an easily applicable nomogram using routinely available indicators. This tool enables early risk stratification for PNICI, facilitating timely interventions that may reduce infection-related complications. However, multicenter prospective validation data are required to further confirm the clinical utility.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250382"},"PeriodicalIF":2.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of melatonin in affecting cognitive dysfunction in acute sleep deprivation mice through the nuclear factor kappaB pathway and oxidative stress.","authors":"Wenting Li, Quan Chen, Haipeng Fu","doi":"10.1515/tnsci-2025-0379","DOIUrl":"10.1515/tnsci-2025-0379","url":null,"abstract":"<p><strong>Objective: </strong>Acute sleep deprivation (ASD) is prevalent in contemporary society. This study explored the mechanism of melatonin affecting cognitive dysfunction (CD) in ASD mice through the nuclear factor kappaB (NF-κB) pathway and oxidative stress.</p><p><strong>Methods: </strong>The ASD mouse model was established and treated with low-dose and high-dose melatonin, a NF-κB inhibitor PDTC, or lipopolysaccharide (LPS), with their spatial memory, spontaneous activity, and anxiety assessed. Hippocampal morphology and neuronal status were observed via HE and Nissl staining. Superoxide dismutase (SOD) activity and levels of hippocampal CA1 region postsynaptic density protein 95 (PSD95), phosphorylated (p)-p65, and p-IκB proteins; acetylcholinesterase (AChE), acetylcholine (ACh), malondialdehyde (MDA), and reactive oxygen species (ROS); and IL-4, IL-10, tumor necrosis factor [TNF]-α, and IL-1β levels were determined by western blot and ELISA kits.</p><p><strong>Results: </strong>ASD mice exhibited reduced learning and memory abilities and spontaneous activities, loosely-arranged cells in the hippocampal CA1 region, unclear cell body boundaries, enlarged gaps, severe neuronal damage, and reduced PSD95 protein level. There were increases in AChE, p-p65, p-IκB, TNF-α, IL-1β, MDA, and ROS levels, decrements in ACh, IL-4, and IL-10 levels and SOD activity in the hippocampal CA1 region of ASD mice. Melatonin or PDTC inhibited the NF-κB pathway, down-regulated TNF-α, IL-1β, MDA, and ROS and up-regulated IL-4 and IL-10 and SOD activity in the hippocampal CA1 region of ASD mice, and improved the learning and memory abilities. LPS-induced NF-κB pathway activation partially averted melatonin's beneficial effects on ASD mice.</p><p><strong>Conclusion: </strong>Melatonin ameliorated ASD-induced CD in mice by modulating the NF-κB pathway and oxidative stress.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250379"},"PeriodicalIF":2.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DIA-based proteomics reveals anti-inflammatory role of DL-3-<i>n</i>-butylphthalide in cerebral small vessel disease-induced brain injury in hypertensive rat.","authors":"Juan Sun, Zhe Su, Yingxiao Ji, Fangming Wang, Jingru Zhao, Jian Zhang, Litao Li","doi":"10.1515/tnsci-2025-0381","DOIUrl":"10.1515/tnsci-2025-0381","url":null,"abstract":"<p><strong>Objectives: </strong>Excessive neuroinflammatory responses represent a key pathological mechanism in cerebral small vessel disease (CSVD). Dl-3-<i>n</i>-butylphthalide (NBP), a compound previously demonstrated to possess anti-inflammatory properties in ischemic stroke, was investigated for its potential therapeutic effects in a rodent model of CSVD. This study aimed to elucidate the neuroprotective mechanisms of NBP in CSVD pathogenesis.</p><p><strong>Methods: </strong>Forty-week-old spontaneously hypertensive rats were selected as a CSVD rodent model to determine the neuroprotective effects of NBP. Cognitive ability was assessed using the Morris water maze after 28 weeks of treatment. Pathological changes in the brain tissue were observed through immunohistochemistry. Data-independent acquisition (DIA) mass spectrometry was executed to identify the probable targets of NBP in CSVD. Based on the proteomics results, the expression of the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway in the rat hippocampus was evaluated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>NBP treatment ameliorated the cognitive abilities and pathological changes in CSVD. DIA proteomics revealed 262 differentially expressed hippocampal proteins, with bioinformatics analysis highlighting acute inflammatory response as a primary target. Furthermore, western blotting and qRT-PCR results confirmed these results and showed that after treatment with NBP, TLR4 regulated NF-κB pathway and inflammatory factors decreased.</p><p><strong>Conclusions: </strong>Our findings demonstrated that NBP exerts neuroprotection in CSVD probably by suppressing TLR4/MyD88/NF-κB-mediated neuroinflammation. This study provides the evidence of NBP's therapeutic mechanisms in CSVD, suggesting its potential as a targeted anti-inflammatory treatment.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250381"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviating the NF-κB/NLRP3 pathway-mediated pyroptosis and ameliorating the cognitive function of aged mice post partial hepatectomy by increasing the Bmal1 level via subanesthetic doses of ketamine.","authors":"Wenbin Zeng, Xiaoming Lei, Hongtao Liu, Simin Zheng, Qianru Wang, Xiaoli Niu","doi":"10.1515/tnsci-2025-0370","DOIUrl":"10.1515/tnsci-2025-0370","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;As a non-competitive blocker of the &lt;i&gt;N&lt;/i&gt;-methyl-d-aspartate receptor, ketamine is widely used for anesthesia and pain relief in clinical settings. However, certain neurological side effects may appear if it is used for the long term. According to clinical observations, anesthetic doses of ketamine trigger postoperative neurocognitive dysfunction in elderly patients, while subanesthetic doses of ketamine suppress the postoperative neuronal pyroptosis in the hippocampus, ameliorating the cognitive function. There is a certain link between brain and muscle arnt-like 1 (Bmal1) and the postoperative cognitive functions of elderly patients. Meanwhile, the Bmal1 activity can be intensified by subanesthetic doses of ketamine. How subanesthetic doses of ketamine act on the postoperative cognitive functions of elderly patients via Bmal1 is to be further investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;To expound how different doses of ketamine affect the cognitive functions of 15-month-old mice (No.: C57BL/6) receiving partial hepatectomy (PH), the following assays were conducted: (1) Morris Water Maze tests were made on mice on days1, 3, and 7 post-surgery; (2) histopathological analyses (by Nissl and Tunel staining) as well as western blotting, immunofluorescence, immunohistochemical, and ELISA assays were carried out on the hippocampal tissue samples collected from the mice 3 days post-surgery. Furthermore, to verify the critical role of the Bmal1 gene in the subanesthetic doses of ketamine-based improvement of cognitive function in aged mice post-surgery, the survey on 15-month-old mice (No.: C57BL/6) with inactivated Bmal1 gene was continued. Through the aforementioned assays, the modulation mechanism of subanesthetic doses of ketamine in ameliorating postoperative cognitive functions of aged mice was elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;As revealed through this investigation, subanesthetic doses of ketamine compared with the sham group effectively enhanced mice's memory and learning ability, increased the expression of p-NR2B and BDNF proteins, mitigated neuronal pathologic injuries and neuroinflammation in aged mice post-surgery, upregulated the gene expression of Bmal1, and inhibited the hippocampal neuronal pyroptosis mediated by the NF-κB/NLRP3 signaling pathway. These effects are contrary to those of anesthetic doses of ketamine. Furthermore, for mice with an inactivated Bmal1 gene, injecting subanesthetic doses of ketamine helped to alleviate neuronal pathological injuries and neuroinflammation in the hippocampal tissues, suppress the expression of cytokines pertaining to the NF-κB/NLRP3 signaling pathway, and improve postoperative memory and learning competence of the mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Subanesthetic doses of ketamine can elevate the expressed level of Bmal1, dampening the NF-κB/NLRP3 pathway-mediated cell pyroptosis, alleviating neuroinflammation, and improving the postoperativ","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250370"},"PeriodicalIF":2.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma tissue factor as a promising marker in multiple sclerosis: Evidence from a two-sample Mendelian randomization study.","authors":"Rui Pan, Aiqi Wang, Yaqi Li, Qizhi Xie, Meihua Lin, Jiayi Li, Xiaolei Shi","doi":"10.1515/tnsci-2025-0378","DOIUrl":"10.1515/tnsci-2025-0378","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a major demyelinating disorder that affects the central nervous system. A growing body of evidence has revealed the involvement of coagulation pathway in the pathogenesis of MS. However, the causal association between coagulation factors and MS is still unclear.</p><p><strong>Method: </strong>A two-sample Mendelian randomization (MR) analysis was conducted. Genetic variants for plasma coagulation factors were identified as instrumental variables. Summary-level statistics for MS were collected from a large-scale genome-wide association study, including 47,429 cases and 68,374 controls. Primary MR analysis was performed using the inverse-variance weighting (IVW) approach. False discovery rate (FDR)-adjusted method was applied to adjust for multiple testing. MR-Egger, weighted median, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as sensitivity analysis approaches.</p><p><strong>Results: </strong>A causal effect of higher plasma tissue factor (TF) levels on the risk of MS onset was identified using IVW method (OR: 1.215, 95% CI 1.108-1.333, <i>P</i> < 0.001, <i>P</i> _FDR < 0.001). Complementary analysis using weighted median (OR: 1.262, 95% CI: 1.119-1.423, <i>P</i> < 0.001), weighted mode (OR: 1.238, 95% CI: 1.100-1.394, <i>P</i> = 0.012), and MR-PRESSO (OR: 1.215, 95% CI: 1.125-1.313, <i>P</i> = 0.003) methods yielded consistent results. Null associations were found for other plasma coagulation factors with MS.</p><p><strong>Conclusions: </strong>The study demonstrates a suggestive association between TF and MS. Increasing plasma TF was associated with an increase in MS risk. TF should be a promising biomarker and new target for MS.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"16 1","pages":"20250378"},"PeriodicalIF":2.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}