Neuroscience最新文献

{"title":"Super-resolution localization microscopy visualizes ischemia-related cytoskeletal and vascular alterations at the nanoscale level in a mouse model of stroke","authors":"Achmed Mrestani ,&nbsp;Corinna Höfling ,&nbsp;Dominik Michalski","doi":"10.1016/j.neuroscience.2025.12.027","DOIUrl":"10.1016/j.neuroscience.2025.12.027","url":null,"abstract":"<div><div>Ischemic stroke results in acute and long-lasting brain damage with consecutive neuronal death. Advancements in visualizing ischemia-related structural alterations at the cellular level are crucial for understanding pathophysiological processes in more detail. Considering the already established concept of the neurovascular unit, both neuronal components and the vasculature are of particular interest. This study combined conventional fluorescence and super-resolution localization microscopy, specifically <em>direct</em> stochastic optical reconstruction microscopy (<em>d</em>STORM), to visualize cell-stabilizing neuronal and vascular elements in the setting of stroke. For this approach, neurofilament light chain (NFL), microtubule-associated protein 2 (MAP2), and collagen IV (CollIV) were detected in non-altered and ischemic brain regions of mice following 24 h of focal cerebral ischemia. Super-resolution localization microscopy enabled the visualization of the cytoskeletal elements NFL and MAP2 as filamentous structures with varying diameters and CollIV associated with the vessel wall. Due to ischemia, gradually enlarged filament diameters and higher molecular densities were observed for NFL, while the number of localizations was largely reduced for MAP2 and gradually increased for CollIV. Although these observations do not allow for conclusions regarding the functional characteristics of targeted structures, ischemia-related structural alterations at the nanoscale, i.e., the molecular level, became visible by <em>d</em>STORM. Super-resolution localization microscopy thus appears to be a valuable method for investigating the ischemic consequences on cytoskeletal elements and the vasculature. The emerging insights could help elucidate the mechanisms underlying stroke-related tissue damage in more detail and identify novel neuroprotective targets.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 77-84"},"PeriodicalIF":2.8,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoacylglycerol lipase inhibition improves motor function and reduces oxidative stress in hemiparkinsonian mice","authors":"Delia Maciel Mendoza-Camacho ,&nbsp;Juan Manuel Viveros-Paredes ,&nbsp;Mario Eduardo Flores-Soto ,&nbsp;Alma Hortensia Martínez-Preciado ,&nbsp;Aldo Rafael Tejeda-Martínez","doi":"10.1016/j.neuroscience.2025.12.025","DOIUrl":"10.1016/j.neuroscience.2025.12.025","url":null,"abstract":"<div><div>Parkinson’s Disease (PD) is characterized by motor symptoms, loss of dopaminergic neurons, and oxidative stress in the Substantia Nigra pars compacta (SNpc) and striatum of patients, as well as in models of parkinsonism. Recent studies show that the endocannabinoid system present in the basal ganglia has a strong influence on the progression of PD, with the inhibition of the enzyme Monoacylglycerol Lipase (MAGL) being a promising therapeutic strategy. Therefore, the aim of this study was to evaluate the effect of MAGL inhibition on locomotion and oxidative stress in a murine model of hemiparkinsonism. For this study, male C57BL/6J mice were divided into four groups: 1) Control group, 2) 6-OHDA group, which received the hemiparkinsonism model, 3) JZL184 group, which received a dose of 8 mg/kg/day for 7 days of the JZL184 inhibitor, and 4) 6-OHDA + JZL184 group, which had the hemiparkinsonism model and, 14 days later, began administration with JZL184. It was found that the hemiparkinsonism mice showed significant improvements both in locomotor performance and in levels of lipoperoxidation, total antioxidant capacity, superoxide dismutase activity, and in quantity and activity of mitochondrial complex I, once the MAGL inhibitor was administered to this group. Treatment with the JZL184 inhibitor demonstrated improved locomotor ability and reduced oxidative stress levels in the SN<em>pc</em> and striatum of mice with hemiparkinsonism. This suggests that MAGL inhibition could be a therapeutic alternative for PD in the future.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 1-10"},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal interference non-invasive deep brainstimulation: bibliometric, clinical translation and potential for neurorestoratology","authors":"Zhanxiang Lin ,&nbsp;Weixian Zeng ,&nbsp;Weili Zhu ,&nbsp;Cheng Tan ,&nbsp;Zicai Liu","doi":"10.1016/j.neuroscience.2025.12.031","DOIUrl":"10.1016/j.neuroscience.2025.12.031","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Temporal interference stimulation (TIS) is a novel, non-invasive neuromodulation technique that effectively overcomes the depth and electric field dispersion issues of conventional transcranial electrical stimulation. TIS holds promise for achieving greater functional recovery than current neural repair methods. This study aims to assess the current status, trends, and hotspots in TIS development, review its evolution, explore its advanced applications in neurorestoratology, and provide theoretical and practical guidance for its future advancement.</div></div><div><h3>Materials and methods</h3><div>A literature search was performed using the Web of Science database to identify TIS-related studies, and CiteSpace and VOSviewer were used for analysis and visualization. Additionally, PubMed databases were searched with subject terms and keywords to explore the development, evolution, and application of TIS technology in neurorestoratology.</div></div><div><h3>Results and conclusions</h3><div>A total of 127 relevant publications were included in the bibliometric analysis. Since the TIS technique was introduced in 2017, the number of related studies has grown annually. The United States and China lead in TIS research output. “Deep brain stimulation” is the most common keyword, highlighting the technique’s objectives and potential. The review results indicate that TIS is a safe and effective non-invasive deep brain stimulation method. Although the technology is still in the stages of computer simulations, animal studies, and small human trials, TIS is poised to become a promising tool for neurorestoratology, as the body of literature has expanded over the past 9 years.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"596 ","pages":"Pages 90-104"},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel hybrid peptide BNT12 displays potent antinociception with limited opioid-like side effects at the spinal level","authors":"Si-Yu Wang ,&nbsp;Wen-Hui Liu ,&nbsp;Jing-Jing Shi ,&nbsp;Jun-Ren Dai ,&nbsp;Dai-Yun Ning ,&nbsp;Si-Yuan Huang ,&nbsp;Che Xu ,&nbsp;Xiao-Fang Wang ,&nbsp;Yu-Jing Wu ,&nbsp;Chang-Lin Wang","doi":"10.1016/j.neuroscience.2025.12.023","DOIUrl":"10.1016/j.neuroscience.2025.12.023","url":null,"abstract":"<div><div>The development of multi-target opioids has emerged as a promising strategy to mitigate opioid-related side effects. We have previously designed a novel hybrid peptide BNT12 by combining opioid and neurotensin pharmacophores, which exhibited supraspinal antinociception. Herein, the antinociceptive properties of a novel hybrid peptide, BNT12, were evaluated across various preclinical pain models following intrathecal (i.t.) administration. Our results showed that spinal administration of BNT12 produced potent antinociception in acute pain. The antinociceptive effects of BNT12 were likely mediated through μ- and δ-opioid receptors, as well as the neurotensin receptor 1 (NTSR1) and 2 (NTSR2). BNT12 also exhibited significant antinociceptive activities in spared nerve injury (SNI)-induced neuropathic pain, complete Freund’s adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain at the spinal level. Additionally, BNT12 significantly inhibited the microglial activation and decreased the mRNA expression levels of TNF-α and IL-1β in the spinal dorsal horn of SNI model. It is noteworthy that BNT12 exhibited substantially reduced acute and chronic antinociceptive tolerance. Furthermore, i.t. administered BNT12 showed minimal or no side effects on conditioned place preference response, naloxone-precipitated withdrawal response, acute hyperlocomotion, gastrointestinal transit, and motor coordination. The present investigation demonstrated that the hybrid peptide BNT12 exhibited potent and durable antinociception with minimal opioid-like side effects at the spinal level. Therefore, BNT12 might serve as a promising candidate to alleviate pain with a favourable side effect profile.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"593 ","pages":"Pages 226-241"},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone-brain crosstalk: emerging roles of osteocalcin in central nervous system disorders","authors":"Hui Chen ,&nbsp;Zhaoxia Zhang ,&nbsp;Wenjin Yi ,&nbsp;Nan Wang ,&nbsp;Xuan Dong ,&nbsp;Ying Xing ,&nbsp;Qingquan Liu ,&nbsp;Yumei Wu ,&nbsp;Xue Ma","doi":"10.1016/j.neuroscience.2025.12.028","DOIUrl":"10.1016/j.neuroscience.2025.12.028","url":null,"abstract":"<div><div>Despite significant advancements in understanding the pathogenesis of various central nervous system (CNS) disorders, challenges remain in the early intervention and targeted therapies for common neurodegenerative and psychiatric conditions such as Parkinson’s disease (PD), Alzheimer’s disease (AD), anxiety, depression, and strokes. Recent studies have increasingly focused on the interaction between the peripheral and central nervous systems, emphasizing the regulatory influence of peripheral mechanisms on CNS disorders. This evolving perspective paves the way for innovative treatment strategies for CNS diseases, with the bone-brain axis emerging as a key regulatory pathway. This axis was first systematically proposed to highlight the role of bone-derived hormones in brain function. Importantly, bone tissue extends its functions beyond mere structural support and movement; it secretes molecules like osteocalcin (OCN) that influence neuronal and glial cell activities. This interaction is vital for regulating multiple CNS processes, including mood, cognition, inflammation, and the formation and differentiation of myelin. Upon release from bone tissue, OCN enters the bloodstream and affects peripheral organs via the Gprc6a receptor, while also crossing the blood–brain barrier to interact with receptors such as Gpr158 and Gpr37 in specific brain areas. This intra-brain interaction significantly impacts the progression and prognosis of various CNS disorders. This article undertakes a comprehensive analysis of OCN modulation in CNS disorders and its underlying mechanisms, laying the groundwork for further exploration of its clinical applications and suggesting new research avenues and therapeutic strategies for CNS diseases.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 1-8"},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognition and postural balance in young adults: Investigating the limits of cognitive involvement in motor automaticity","authors":"Nahid Divandari ,&nbsp;Marie–Louise Bird ,&nbsp;Maryam Zoghi ,&nbsp;Fefe Vakili ,&nbsp;Shapour Jaberzadeh","doi":"10.1016/j.neuroscience.2025.12.019","DOIUrl":"10.1016/j.neuroscience.2025.12.019","url":null,"abstract":"<div><div>Links between cognition and balance are well established in older adults and athletes, but evidence in healthy young adults is limited.</div><div>This cross-sectional study examined the relationship between cognitive domains (processing speed, working memory, and inhibition) and static and dynamic balance in 62 adults aged 18–45 years. Participants completed cognitive tests (Deary-Liewald, Stroop, N-back) and balance assessments (Sway Medical App, Y Balance Test). Correlation and hierarchical multiple regression analyses revealed no significant association between cognition and balance, while a higher BMI was associated with poorer dynamic balance.</div><div>These findings suggest that in early adulthood, postural stability during single-task assessments may rely on automated motor control rather than cognitive processes. This could support the idea of early adulthood as a period of motor autonomy. Future research should test complex or dual-task conditions to identify potential cognitive involvement and inform early interventions for lifelong motor-cognitive health.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"593 ","pages":"Pages 204-211"},"PeriodicalIF":2.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the expression and function of schizophrenia risk gene Dtnbp1 in the suprachiasmatic nucleus","authors":"Genavieve Elizabeth Maloney ,&nbsp;Marie-Ève Cloutier ,&nbsp;Micah Joseph Provost ,&nbsp;Lalit K. Srivastava ,&nbsp;Nicolas Cermakian","doi":"10.1016/j.neuroscience.2025.12.029","DOIUrl":"10.1016/j.neuroscience.2025.12.029","url":null,"abstract":"<div><div>Schizophrenia (SZ) is a debilitating neurodevelopmental disorder with environmental and genetic origins. Circadian rhythm disruption is observed in a large proportion of patients with SZ. We previously found that Sandy (Sdy) mice, which carry a mutation in the SZ-associated gene <em>dystrobrevin binding protein 1</em> (<em>Dtnbp1,</em> also called <em>Dysbindin-1</em>), show altered rhythms of locomotor activity. To address the possible mechanisms underlying the circadian phenotype of these mice, we set out to address the expression and function of <em>Dtnbp1</em> in the suprachiasmatic nucleus (SCN), the location of the central circadian clock in mammals. Immunohistochemistry revealed that DTNBP1 protein was expressed throughout the SCN, with stronger expression in the dorsal part. DTNBP1 immunoreactive signal colocalized with neurons expressing either arginine vasopressin peptide (AVP) or vasoactive intestinal peptide (VIP). Fluorescent in situ hybridization showed a time-dependent variation of expression of <em>Dtnbp1</em> transcript, and confirmed its location in cell bodies of AVP- and VIP-expressing cells. Since DTNBP1 is known to be implicated in synaptic transmission, we studied the effect of <em>Dtnbp1</em> gene mutation on SCN neuropeptide expression and neuroanatomy in Sdy mice. There was no significant effect of the <em>Dtnbp1</em> mutation on AVP and VIP expression in the SCN. We then used transmission electron microscopy to study synaptic morphology and secretory vesicles. There was no effect of the <em>Dtnbp1</em> mutation on these neuroanatomical features. Our data show that <em>Dtnbp1</em> is expressed with a daily rhythm across the SCN, but that a loss-of-function mutation did not impair AVP or VIP neuropeptide expression nor general synaptic architecture.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 250-261"},"PeriodicalIF":2.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural dynamics of unintentional empathy for physical and social pain","authors":"Nan Zhang ,&nbsp;Jiayue Huang ,&nbsp;Dongfang Zhao ,&nbsp;Wenbo Luo","doi":"10.1016/j.neuroscience.2025.12.026","DOIUrl":"10.1016/j.neuroscience.2025.12.026","url":null,"abstract":"<div><div>Empathy for pain supports interpersonal interaction and underpins prosocial behavior. Yet the neural mechanisms of unintentional empathy for pain remain unclear, and it is unknown whether they differ by pain category. To characterize the temporal dynamics of two forms of unintentional pain empathy, we used a 1-back task to probe neural responses to physical versus social pain contexts. Event-related potential (ERP) analyses showed that unintentional empathy for physical pain was primarily reflected in the occipito-temporal N170, frontal–central P2, and parietal late positive potential (LPP). By contrast, unintentional empathy for social pain was mainly indexed by the frontal–central N400 and the parietal LPP. These findings indicate that unintentional empathy for physical pain emerges earlier and persists longer, consistent with a two-stage processing model, whereas unintentional empathy for social pain shows more pronounced differences only at later stages. Together, the results suggest that pain category significantly modulates unintentional empathy for pain.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 11-17"},"PeriodicalIF":2.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Implications of the mediodorsal thalamic nucleus subdivisions in regulating prefrontal cortex GAD67 and GABAB receptors expression: behavioral and cognitive outcomes","authors":"Hanane Iben-Daoudi ,&nbsp;Mohamed Bennis ,&nbsp;Marc Landry ,&nbsp;Fatima-Zahra Lamrghari ,&nbsp;Saadia Ba-M’hamed ,&nbsp;Zakaria Ouhaz","doi":"10.1016/j.neuroscience.2025.12.024","DOIUrl":"10.1016/j.neuroscience.2025.12.024","url":null,"abstract":"<div><div>The mediodorsal thalamus plays a pivotal role in cognitive and emotional processes. Its heterogeneous subdivisions, medial, central, and lateral, exhibit distinct connectivity with prefrontal regions. However, their specific contributions to behavior and cortical inhibition remain unclear. NMDA-induced excitotoxic lesions in adult male and female Sprague-Dawley rats were made to selectively disrupt specific subdivisions of the MD (total MD, MDmc, and MDl). Subsequently, we evaluated changes in behavioral outcomes using the open field, elevated plus maze, social interaction, Y-maze, and passive avoidance tests. Alterations in GABAergic markers were also assessed by quantifying GAD67-expressing interneurons and GABA_B receptor densities across cortical layers of the anterior cingulate cortex and prelimbic cortex using immunohistochemical procedures. MD lesions significantly impaired working memory, associative learning, and social behaviors. Specifically, MDl lesions induced significant hyperactivity, particularly in females. MDmc and total MD lesions increased anxiety-like behaviors, whereas MDl lesions decreased anxiety in males. Neurochemically, all MD lesions increased GAD67 expression and decreased GABA_B receptor densities in layers 2/3 and 5 of the anterior cingulate cortex and the prelimbic cortex, with marked sex-dependent effects. These findings illustrate the functional specificity of MD subdivisions in modulating prefrontal circuits critical for behavior, providing novel insights into thalamocortical mechanisms and their relevance to neuropsychiatric disorders characterized by GABAergic dysfunction.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 203-223"},"PeriodicalIF":2.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating multimodal data to identify single nucleotide polymorphism-related biomarkers and regulatory mechanisms in Alzheimer’s disease","authors":"Jinhua Sheng ,&nbsp;Luyun Wang ,&nbsp;Qiao Zhang ,&nbsp;Jay Tsai Chien Chou ,&nbsp;Rong Zhang ,&nbsp;Tao Li ,&nbsp;Yan Lu","doi":"10.1016/j.neuroscience.2025.12.022","DOIUrl":"10.1016/j.neuroscience.2025.12.022","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common neurodegenerative disease with unclear regulatory mechanisms at the cell-type level. A multi-omics model called single nucleotide polymorphisms (SNPs)–transcriptomic–single-nucleus ribonucleic acid sequencing (snRNA-seq) integration (STSNI) is proposed to identify SNPs-related biomarkers and regulatory mechanisms in AD. Differential expression analysis identified differentially expressed genes (DEGs) between AD patients and healthy controls (HCs) in the GSE118553 dataset. Cell-type annotation in the GSE138852 dataset revealed several cell subclusters, and DEGs were identified within these subclusters. Intersection analysis among DEGs from the GSE118553 dataset, cell-subcluster-specific DEGs from the GSE138852 dataset, and SNP-associated genes from the ADNI2 dataset yielded 14 overlapping genes. Using the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms, six biomarkers were identified. Functional enrichment and gene set enrichment analysis (GSEA) linked these biomarkers to pathways such as carboxylic acid catabolic process, exocytic vesicle membrane, and carbon metabolism. Meanwhile, six cell types were identified, including astrocytes, endothelial cells, oligodendrocytes, oligodendrocyte progenitor cells (OPCs), microglia, and neurons. The biomarker-transcription factor (TF) network indicated that Cispb M4676 regulates IQGAP2, NRXN1, GRIA3 and FGF14. Overall, our study identified six SNP-related biomarkers (IQGAP2, HHAT, FGF14, CTNNA3, GRIA3, and NRXN1) associated with AD. The STSNI framework provided novel insights into the cellular and molecular mechanisms underlying AD.</div><div>Significance Statement:</div><div>As the global population continues to age, Alzheimer’s disease (AD) has emerged as a major public health concern. The pathological changes associated with AD include the formation of extracellular amyloid plaques, intracellular neurofibrillary tangles, and neuronal loss with gliosis proliferation. Bioinformatics methods are used to explore the immune infiltration characteristics, biological pathways and regulatory mechanisms of single nucleotide polymorphisms (SNPs) related key genes in AD. The pathogenesis of AD from the overall level and single-cell level is explored based on SNPs-related genes, combined with snRNA-seq data and transcriptome data. This study provides an opportunity for the discovery of novel diagnostic molecular markers and potential treatment targets to serve as the foundation for the development of more effective management techniques for AD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"593 ","pages":"Pages 141-159"},"PeriodicalIF":2.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}