Journal of Molecular Neuroscience最新文献

{"title":"Nicotinamide Riboside (NR) Supplementation Exerts Neuroprotective Effects in db/db Mouse Model of Type 2 Diabetes","authors":"Eleni Hughes,&nbsp;Keely Barton,&nbsp;Daliya Rizvi,&nbsp;Katelyn Dial,&nbsp;Xiaoxin X. Wang,&nbsp;Komuraiah Myakala,&nbsp;Brent T. Harris,&nbsp;G. William Rebeck,&nbsp;Moshe Levi","doi":"10.1007/s12031-026-02499-9","DOIUrl":"10.1007/s12031-026-02499-9","url":null,"abstract":"<div><p>Type 2 diabetes is linked to neuropsychiatric complications such as anxiety-like behaviors, disrupted brain metabolism, neuroinflammation, and impaired mitochondrial function. Nicotinamide riboside (NR) has emerged as a potential therapeutic agent for these complications due to its role in NAD + biosynthesis and neuroprotective properties. In this study, we assessed whether NR supplementation can ameliorate anxiety-like behavior in a mouse model of type 2 diabetes by modulating the hippocampal inflammatory response. 8-week-old db/db mice on the BKS background were used as a model of type 2 diabetes, and db/m mice were used as non-diabetic controls. Four groups, consisting of non-diabetic and diabetic mice, were fed with a control diet or a diet supplemented with NR at 500 mg/kg dosage for 20 weeks. The open field test and nesting behavioral assessments were conducted to evaluate anxiety-related behaviors and overall well-being. After animals were euthanized, biochemical analyses were performed on hippocampal samples using RT-qPCR, Western blotting, and immunohistochemistry. Behavioral assessments revealed increased anxiety and reduced nest-building motivation in db/db mice compared with control mice. These effects were ameliorated by NR treatment. Biochemical analyses revealed that NR attenuated markers of inflammation, including astrocytosis and microglial activation, activation of inflammatory signaling via STING and NF-kB, and pro-inflammatory cytokines. Our findings show that NR supplementation reduces anxiety-like symptoms and neuroinflammation in diabetic mice, highlighting the potential therapeutic relevance of NR in mitigating neuropsychiatric complications associated with diabetes mellitus.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759210","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":"Correction: Cutaneous α-Synuclein Pathology as a Differential Marker: A Histological and Statistical Comparison across Neurodegenerative Disease Groups","authors":"Dorota Šebelová,&nbsp;Kateřina Menšíková,&nbsp;Michaela Kaiserová,&nbsp;Lenka Satke,&nbsp;Zuzana Grambalová,&nbsp;Kateřina Čížková,&nbsp;Zdeněk Tauber,&nbsp;Kateřina Klíčová,&nbsp;Dominik Hraboš,&nbsp;Sarah E. V. Cook,&nbsp;Jana Zapletalová,&nbsp;Petr Kaňovský","doi":"10.1007/s12031-026-02515-y","DOIUrl":"10.1007/s12031-026-02515-y","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759137","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":"Construction of a Computationally Inferred Single-Cell miRNA Activity Atlas and Analysis of Regulatory Networks in Spinal Cord Injury","authors":"Changli Xu,&nbsp;Bingxuan Wang,&nbsp;Zhengqiang Li,&nbsp;Suchi Qiao,&nbsp;Jianli Bu","doi":"10.1007/s12031-026-02528-7","DOIUrl":"10.1007/s12031-026-02528-7","url":null,"abstract":"<div>\u0000 \u0000 <p>Background. Spinal cord injury (SCI) is a debilitating neurological disorder characterized by complex pathological processes involving dynamic responses of multiple cell types and intricate regulatory networks. Although single-cell RNA sequencing (scRNA-seq) has been employed to dissect cellular heterogeneity in SCI, the activity and regulatory functions of microRNAs (miRNAs) at single-cell resolution remain largely unexplored. Methods. This study utilized the GSE189070 dataset, integrating single-cell transcriptomic data from mouse spinal cord tissues at eight time points: uninjured control and 0.5, 1, 3, 7, 14, 60, and 90 days post-injury. Following quality control, batch correction, and cell-type annotation, miRNA activities across 12 major cell types were computationally inferred using a motif enrichment-based approach. Temporal clustering of miRNA activity was performed with Mfuzz, and subsequent analyses included target gene prediction, functional enrichment, and network construction. Inferred miRNA activity patterns were validated using an independent bulk miRNA sequencing dataset (GSE90452). Key findings were experimentally verified in BV-2 microglial cells and C8-D1A astrocytes using miRNA inhibitors and mimics. Results. We successfully constructed a single-cell transcriptomic atlas and a dynamic computationally inferred miRNA activity landscape during SCI progression. Independent dataset validation confirmed that inferred miRNA activity changes (e.g., mmu-miR-488-3p, mmu-miR-132-3p) were consistent with actual miRNA expression alterations. Our analysis revealed that microglia and macrophages exhibited dynamic miRNA activity patterns closely associated with inflammatory pathways, including TNFA_SIGNALING_VIA_NFKB and TOLL-LIKE RECEPTOR signaling. Cross-cell-type comparison identified 38 common differentially active miRNAs shared between microglia and macrophages, with network analysis revealing coordinated regulation of key inflammatory genes (e.g., Lif, Csf1, Il18rap). In astrocytes, specific miRNAs (e.g., miR-7a-5p, miR-124-3p) were found to regulate apoptotic pathways by targeting Casp3 and Bcl2 family genes. Experimental validation confirmed that miR-130a-3p promotes microglial inflammation, while miR-7a-5p inhibits astrocyte apoptosis under oxidative stress. Conclusion. This study presents a computationally inferred, experimentally validated single-cell-resolution map of miRNA activity dynamics during SCI, revealing potential regulatory networks in key cell types. The concordance between computational inference and independent experimental data supports the biological plausibility of our findings and provides a foundation for further therapeutic exploration.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759099","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":"Unveiling the Gut-Brain Axis: Fusobacteriaceae Promotes Parkinson’s Disease Development via CA9 Suppression-Induced Ferroptosis","authors":"Ren Zihan,&nbsp;Li Pengfei,&nbsp;Cao Jingsi","doi":"10.1007/s12031-026-02530-z","DOIUrl":"10.1007/s12031-026-02530-z","url":null,"abstract":"&lt;div&gt;&lt;p&gt;The conceptual framework of the ‘gut-brain axis’ proposes that an imbalance in the gut microbiota plays a contributory role in the etiology of Parkinson’s disease (PD). However, the specific molecular mechanisms, particularly those involving ferroptosis, remain largely unknown. We adopted a robust two-sample Mendelian randomization (MR) strategy, analyzing extensive summary-level GWAS data to unravel the causal connections tying the gut microbiota and ferroptosis-associated proteins to the risk of PD. Our analysis pinpointed 22 distinct gut microbial taxa and five proteins involved in ferroptosis that are genetically predicted to influence PD susceptibility. Notably, the family &lt;i&gt;Fusobacteriaceae&lt;/i&gt; was identified as a robust risk factor. Further mediation analysis suggested that the ferroptosis-related protein carbonic anhydrase 9 (CA9) mediates the genetically predicted effect of &lt;i&gt;Fusobacteriaceae&lt;/i&gt; on PD. Specifically, an elevated genetic predisposition to &lt;i&gt;Fusobacteriaceae&lt;/i&gt; is associated with a downregulation of plasma CA9, a molecular shift that is genetically predicted to heighten the risk of developing PD. The calculated mediation proportion was 11.7%, and the robustness of this result was upheld by comprehensive sensitivity assessments. This study provides novel genetic evidence supporting a potential “gut microbiota–ferroptosis–PD” axis. We propose that &lt;i&gt;Fusobacteriaceae&lt;/i&gt; may aggravate PD progression by downregulating CA9, thereby compromising CA9-dependent anti-ferroptotic defense mechanisms. Collectively, our results provide fresh perspectives on the molecular mechanisms underpinning the gut-brain axis, highlighting promising avenues for therapeutic intervention in PD. &lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;&lt;p&gt;The proposed Fusobacteriaceae-CA9-Ferroptosis axis in Parkinson’s disease pathogenesis. A genetically predicted overabundance of Fusobacteriaceae compromises intestinal barrier integrity, facilitating the systemic translocation of lipopolysaccharides (LPS). Upon crossing the blood-brain barrier (BBB), circulating LPS triggers microglial activation and the sustained release of pro-inflammatory cytokines (e.g., TNF-α, IL-1β). This chronic neuroinflammatory microenvironment represses the transcription and expression of the pH-regulating protein carbonic anhydrase 9 (CA9) in dopaminergic neurons. The subsequent CA9 downregulation induces severe intracellular acidification, which dualistically expands the labile iron pool (LIP) via ferritin degradation and cripples the antioxidant defense system by depleting glutathione (GSH) and inactivating GPX4. Ultimately, the confluence of elevated ferrous iron (Fe²⁺) and an acidic milieu aggressively accelerates the Fenton reaction, driving massive lipid peroxidation of polyunsaturated fatty acids (PUFAs) and culminating in neuronal ferroptosis&lt;/p&gt;&lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;source&gt;&lt;img&gt;&lt;/source&gt;&lt;/picture&gt;&lt;span&gt;The alternative text for this image may have been generated usin","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759170","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":"Reimagining GSK-3β Therapeutics in Alzheimer’s Disease: From Inhibition to Activity Normalization and Targeted Degradation","authors":"Emad Manni,&nbsp;Hayder M. Al-kuraishy,&nbsp;Rabab Eisawy,&nbsp;Ahmed M. Abdelaziz,&nbsp;Gaber El-Saber Batiha","doi":"10.1007/s12031-026-02518-9","DOIUrl":"10.1007/s12031-026-02518-9","url":null,"abstract":"<div>\u0000 \u0000 <p>Glycogen Synthase Kinase-3β (GSK-3β) acts as a critical pathogenic amplifier in Alzheimer’s disease (AD), linking and intensifying various degenerative processes such as amyloid-β formation, tau hyperphosphorylation, and neuroinflammation. Rather than serving solely as an upstream trigger, the hyperactivity of GSK-3β interacts with other dysregulated kinases, including CDK5, DYRK1A, and MARKs, to worsen neurodegeneration. This collaboration leads to increased neuronal cell death and cognitive decline in AD patients. However, the clinical translation of conventional GSK-3β inhibitors has been thwarted by a fundamental paradox: complete enzymatic blockade induces Wnt-mediated toxicity, while partial inhibition often fails due to compensatory feedback. This review argues for a paradigm shift: from broad kinase suppression to precise activity normalization. We critically analyze the translational failures of catalytic inhibitors, then examine emerging strategies capable of restoring physiological kinase homeostasis. Foremost among these are brain-penetrant Proteolysis-Targeting Chimeras (PROTACs), which eliminate both the catalytic and non-catalytic (scaffold) functions of GSK-3β through targeted proteasomal degradation, thereby addressing pathological activities that conventional inhibitors leave intact. Furthermore, we explore the synergistic potential of multi-target-directed ligands (MTDLs) and indirect modulation via the gut-brain axis to widen the therapeutic window. By recalibrating rather than silencing GSK-3β, this framework outlines a mechanistically grounded roadmap for achieving safe and effective disease modification in AD, moving this central kinase from an undruggable liability to a central component of future therapeutic strategies.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738385","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":"Sesn2 is Associated with Attenuated Muscle Atrophy and Altered Expression of Key Myogenic and Autophagy Markers in Mdx Mice","authors":"Zubiao Song,&nbsp;Qing Lin,&nbsp;Jiahui Liang,&nbsp;Juanjuan He,&nbsp;Weixi Zhang","doi":"10.1007/s12031-026-02522-z","DOIUrl":"10.1007/s12031-026-02522-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Duchenne muscular dystrophy (DMD) is a common lethal neuromuscular disorder which is characterized by progressive skeletal muscle atrophy. Despite the beneficial role of Sestrin2 (Sesn2) in improving denervation-induced skeletal muscle atrophy, the effect of Sesn2 on the skeletal muscle of DMD remains largely unknown. To regulate the expression of Sesn2, we systemically modulated its expression in <i>mdx</i> mice via tail-vein injection of AAV9 vectors. The tibialis anterior (TA) muscles were subsequently harvested for analysis by immunofluorescence and Western blotting to assess myofiber morphology and the protein levels of key markers of atrophy, myogenesis, and autophagy. In this study, we found that the expression levels of Sesn2 were significantly upregulated in the tibialis anterior muscle of <i>mdx</i> mice. Sesn2 overexpression was associated with increased myofiber cross-sectional area and reduced levels of the atrophy-related markers MuRF1 and Atrogin-1, whereas Sesn2 knockdown aggravated the expression of MuRF1 and Atrogin-1. At the molecular level, Sesn2 overexpression significantly upregulated the expression of myogenic differentiation factors (Myog and Myf5), whereas its knockdown significantly downregulated them, indicating the positive regulatory effect of Sesn2 on myogenic signaling. Additionally, the inhibition of Sesn2 significantly suppressed key autophagy markers (downregulation of pUlk1, Bec1 and LC3-II expression and accumulation of p62). Collectively, these data suggest that Sesn2 is associated with improvement in dystrophic muscle histology by coordinately influencing cellular process related to protein degradation, myogenesis and autophagy, presenting it as a potential therapeutic candidate for DMD.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737857","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":"Advancements in the Study of Missense Mutations in ABCA7 in Alzheimer’s Disease","authors":"Lixin Liu,&nbsp;Bin Zhu","doi":"10.1007/s12031-026-02526-9","DOIUrl":"10.1007/s12031-026-02526-9","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer’s disease (AD) is a neurodegenerative disorder affecting millions of people worldwide. In recent years, genetic factors, particularly missense mutations in susceptibility genes, have been proven to play a key role in the pathogenesis of AD. The <i>ABCA7</i>, a regulator of lipid metabolism and amyloid-beta clearance, has missense mutations that impact phospholipid transport and phagocytic functions, thus contributing to the development of AD. Genome-wide association studies (GWAS) and whole-genome sequencing have identified various missense mutations in <i>ABCA7</i>, such as G1527A and R880Q, with risk ratios up to 1.15 times. Furthermore, differences in the distribution of these mutations across different ethnic groups have been widely reported. Future research should focus on the prevalence and functional effects of these mutations in different populations and their specific effects on <i>ABCA7</i> protein function. A deeper understanding of these mutations could provide new scientific bases for the early diagnosis and treatment of AD. In summary, the missense mutations in <i>ABCA7</i> provide important insights into the genetic susceptibility of AD and represent potential candidate targets for the development of personalized treatment strategies.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737856","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":"Nicotinic Acetylcholine Receptor of α7 Subtype is Linked to Glioblastoma Cholinergic Heterogeneity","authors":"Elena Gondarenko,&nbsp;Diana Mazur,&nbsp;Andrei Siniavin,&nbsp;Polina Arkhangelskaya,&nbsp;Valery Maiorov,&nbsp;Igor Ivanov,&nbsp;Igor Kasheverov,&nbsp;Nadine Antipova,&nbsp;Irina Shelukhina,&nbsp;Denis Kudryavtsev","doi":"10.1007/s12031-026-02523-y","DOIUrl":"10.1007/s12031-026-02523-y","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma multiforme (GBM) shows tremendous heterogeneity in terms of morphology and gene expression. One of the diagnostically significant characteristics of GBM is the choline peak that can be found in patients’ NMR. Choline derivatives are distributed unevenly throughout the tumor and concentrated, in particular, at the leading edge and infiltrating GBM tumour zones as well as gene transcripts of α7 nicotinic acetylcholine receptor (nAChR), known for its ability to become activated upon choline binding. Since agonist-induced nAChR up-regulation in brain and cell lines has been described and several studies have highlighted the role of nAChR ligands in glioblastoma proliferation in vivo, here we hypothesize for the first time that the complex architecture of glioblastoma might develop partially through choline activation of calcium-permeable α7 nAChR that may contribute to changes in gene expression networks. Using the U87MG glioblastoma cell line, we demonstrated that selective α7 nAChR ligands – agonist (PNU282987) and positive allosteric modulator (PNU120596), and antagonist of α7 and α9 nAChRs (α-cobratoxin, α-CTX, from <i>Naja naja</i> venom) – dynamically regulate nAChR subunit mRNA expression (CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNA9). α-CTX suppressed agonist-induced CHRNA7 up-regulation in U87MG cells and increased cell viability. Proteomic analysis revealed altered expression of cytoskeletal (ACTG1), metabolic (SHMT2, GLRX3), and endoplasmic reticulum-associated (GANAB) proteins, suggesting the involvement of calcium-dependent signaling downstream of α7 nAChR activation. Quantitative PCR, proteomics and cell viability data were integrated by cellular automata model imitating glioblastoma growth and exposed details of tumour progression, which supports a role for α7 nAChR as one of multiple factors that can help shape intratumoural heterogeneity. These results may have implications for the development of personalized treatment strategies. However, since these findings were obtained in a single cell line, further validation in additional GBM models and in vivo systems is needed before broader conclusions can be drawn.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738275","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":"Temporal Biomarker Profiles Following Non-Surgical Spinal Cord Concussion","authors":"Taylor M. Dickson,&nbsp;Anastasiya Loos,&nbsp;Malaika Amin,&nbsp;Juliana Vivas Lopez,&nbsp;Susan F. Murphy,&nbsp;Pamela J. VandeVord,&nbsp;Kelly C. S. Roballo","doi":"10.1007/s12031-026-02520-1","DOIUrl":"10.1007/s12031-026-02520-1","url":null,"abstract":"<div>\u0000 \u0000 <p>Traumatic spinal cord concussion (SCC) can result from motor vehicle accidents, contact sports, falls, and other mild traumatic events. Although clinically significant, the relationship between SCC severity and long‑term outcomes remains unclear. Identifying biochemical biomarkers that reflect post‑injury physiological and molecular changes may improve assessment and guide therapeutic decisions. Similar to advances in traumatic brain injury, integrating biomarkers with imaging and behavioral evaluations could enhance SCC characterization. This study examined biomarkers linked to neuroinflammation and repair mechanisms, ubiquitin C‑terminal hydrolase L1 (UCH‑L1), nitric oxide (NO), glial fibrillary acidic protein (GFAP), and brain‑derived neurotrophic factor (BDNF), and characterized their temporal profiles in a preclinical SCC model. Male Sprague–Dawley rats were assigned to either a blast‑induced SCC group or a sham group. Animals were euthanized at 24 h, 72 h, or 6 weeks post‑injury for spinal cord culture preparation and blood collection. UCH‑L1 and other neuronal injury markers remained elevated from the acute through chronic phases in spinal cord cultures and ex vivo serum, indicating neuronal damage. NO displayed a biphasic pattern with an early increase at 24 h, a decrease at 72 h, and renewed elevation at six weeks, suggestive of inflammatory and oxidative stress responses. GFAP levels rose progressively across all time points, consistent with glial activation. In contrast, BDNF levels showed minimal change, suggesting limited neurotrophic support after SCC. Overall, these biomarker expressions on the SCC cell culture and ex vivo serum indicate an ongoing neuronal stress, chronic inflammation, and glial reactivity. UCH‑L1 appears particularly promising for detecting and monitoring SCC‑related injury, while NO and GFAP offers complementary insight into inflammatory response. Combined with clinical assessments, these biomarkers may improve injury stratification and prediction of long‑term outcomes.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697555","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":"Integrated Transcriptomics and Machine Learning Reveal Lipid Metabolism Related Genes in Ischemic Stroke","authors":"Qiu-Lin Wang,&nbsp;Chang-Le Fang,&nbsp;Tian-Hao Bao,&nbsp;Rui-Ze Niu","doi":"10.1007/s12031-026-02519-8","DOIUrl":"10.1007/s12031-026-02519-8","url":null,"abstract":"<div>\u0000 \u0000 <p>Lipid metabolism dysregulation is considered a key metabolic feature of ischemic stroke (IS) and may also contribute to its related neuropsychiatric complications. However, its critical regulatory molecules remain unclear. By integrating machine learning methods with transcriptomic analyses, this study systematically characterized the molecular networks underlying lipid metabolism in IS. Using bulk RNA-seq data obtained from the middle cerebral artery occlusion model, we observed a significant increase in lipid metabolic activity. By combining differential gene expression analysis, Weighted Gene Co-expression Network Analysis, and machine learning algorithms, we ultimately identified Hmox1, Stat3, and Tlr2 as core genes associated with lipid metabolism dysregulation. Functional enrichment analysis highlighted the strong association between these genes and lipid metabolism pathways. Further single-cell transcriptomic analyses emphasized the significant role of MG in the lipid metabolism disorder of IS. Furthermore, differential gene expression, functional enrichment analysis, and virtual knockout indicated that Hmox1, Stat3 and Tlr2 in microglia were closely related to lipid metabolic activity. In summary, this study identified Hmox1, Stat3, and Tlr2 as potential regulatory targets for microglial lipid metabolism in IS, providing a novel theoretical foundation for understanding the IS mechanism and its potential neuropsychiatric complications and for developing targeted intervention.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687683","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}