Journal of Molecular Neuroscience最新文献

{"title":"Identification of Transcriptome-Derived Candidate Genes Associated with Post-Translational Modification Gene Sets in Neonatal Hypoxic-Ischemic Encephalopathy","authors":"Baoying Zhang,&nbsp;Xueli Ding,&nbsp;Yang Hu,&nbsp;Yi Wei,&nbsp;Yu Tang,&nbsp;Maoqiong Chen,&nbsp;Jianwei Xu","doi":"10.1007/s12031-026-02611-z","DOIUrl":"10.1007/s12031-026-02611-z","url":null,"abstract":"<div><p>Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological injury in newborns. Post-translational modifications (PTMs) precisely regulate protein activity, localization, and interactions during cellular stress. However, transcriptomic changes in genes associated with PTM pathways in HIE remain incompletely characterized. Gene expression data from two mouse datasets (GSE23317 and GSE144456) were acquired from GEO. Candidate screening combined differential expression, WGCNA, and overlap with 21 PTM-related gene sets. Further analyses included PPI networks, expression comparisons, receiver operating characteristic (ROC) analyses, functional enrichment, immune-cell deconvolution, miRNA prediction, molecular docking, and molecular dynamics (MD) simulation. A total of 113 time-consistent differentially expressed genes were identified, and 12 overlapped the HIE-associated WGCNA module and PTM-related gene sets. Five genes, Hk2, Lgals3, Sdc4, Upp1, and Vim, showed positive expression changes in the analysed contrasts (discovery log2 fold-change ranges, 0.271–1.027 at 3 h and 0.326–2.031 at 24 h). Individual-gene areas under the ROC curve (AUCs) ranged from 0.893 to 1.000 in GSE23317; the combined model yielded a leave-one-out cross-validation AUC of 0.929. Functional analyses highlighted glial and cytoskeletal processes, carbohydrate metabolism, and oxidative phosphorylation, and linked the five genes to estimated immune-cell signals. HK2–calcitriol and HK2–menogaril yielded the lowest docking scores, both − 8.9 kcal/mol. Integration of transcriptomic data with PTM-related gene sets identified five candidate genes and highlighted glial, cytoskeletal, metabolic, and immune-associated responses in neonatal HIE. These findings provide a basis for investigating their biological roles and potential biomarker relevance. Integration of transcriptomic data with PTM-related gene sets identified five candidate genes and highlighted glial, cytoskeletal, metabolic, and immune-associated responses in neonatal HIE. These findings provide a basis for investigating their biological roles and potential biomarker relevance.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189568","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":"“Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer’s Disease”","authors":"Karen León-Arcia,&nbsp;Humberto Martínez-Orozco,&nbsp;Magdalena Guerra-Crespo,&nbsp;Sofía Y. Díaz-Miranda,&nbsp;Luis O. Soto-Rojas","doi":"10.1007/s12031-026-02610-0","DOIUrl":"10.1007/s12031-026-02610-0","url":null,"abstract":"<div><p>Blood-brain barrier (BBB) dysfunction is increasingly recognized as an early pathological event in sporadic Alzheimer’s disease (AD), which represents over 95% of cases. Vascular risk factors and cerebral insulin resistance are considered potential contributors to its initiation. This review synthesizes evidence available through March 2026 on the temporal progression of morphological, functional, and molecular BBB alterations in AD patients and experimental models. This review emphasizes the proposed role of BBB disruption in perpetuating neurodegeneration through feedback loops involving pericyte damage, hypoxia, perivascular inflammation, and dysregulation of amyloid-β transport systems. By integrating data from neuroimaging, fluid biomarkers, and post-mortem studies, available evidence suggests that BBB alterations can be detected from preclinical stages, most consistently in the hippocampus, and may exhibit sex-specific differences. The review compares findings from familial transgenic models with the more limited characterization available in sporadic AD models (notably the intracerebroventricular streptozotocin model), and highlights key knowledge gaps regarding temporal dynamics. This synthesis supports further exploration of strategies to preserve BBB integrity. An integrated vascular approach may usefully complement current amyloid- and tau-centered therapies, particularly in sporadic AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-026-02610-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178694","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":"Acute Ultra Low Dose THC Attenuates Anxiety-Like Behavior in a Mouse Model for Major-Depressive Disorder","authors":"Meitar Grad,&nbsp;Hadas Volkov,&nbsp;Noam Shomron","doi":"10.1007/s12031-026-02597-8","DOIUrl":"10.1007/s12031-026-02597-8","url":null,"abstract":"<div><p>Major depressive disorder (MDD) is a prevalent psychiatric disorder, and is a leading cause of disability worldwide. Current treatments for MDD entail many side effects, and include a lag until the onset of therapeutic effects. The current hypotheses as for the etiology of MDD revolve around the monoamine hypothesis and the plasticity and neurodegeneration hypothesis. According to the latter, employing a neuroprotective treatment may help ameliorate depressive symptoms. Δ⁹-Tetrahydrocannabinol (THC) is the primary psychoactive component of the <i>cannabis sativa</i> plant. THC interacts with the endocannabinoid system, which was shown to be involved in the regulation of emotional states (e.g. anxiety) and stress through modulation of synaptic plasticity. Here, we show the potential of acute, ultra-low dose (0.002 mg/kg) THC in ameliorating anxious behavior in a chronic mild stress mouse model for MDD. We utilize next generation sequencing techniques to show the treatment’s effect on neuronal differentiation and synaptic plasticity-related mRNAs, and specify <i>Elmo domain containing 1</i> (<i>Elmod1</i>) as a molecular mediator of the observed anxiolytic effects. Moreover, we show the involvement of glucocorticoids-related mRNAs in the observed anxiolytic effect of acute, ultra-low dose THC.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163667","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":"Comprehensive Transcriptomic Analysis Identifies Potential Biomarkers and Underlying Mechanisms of Acupuncture in Treating Peripheral Facial Paralysis","authors":"Xihong Li,&nbsp;Yan Li,&nbsp;Xinyu Zou,&nbsp;Juanjuan Liu,&nbsp;Runyu Yin,&nbsp;Qinglin Wei,&nbsp;Yonghua Hu","doi":"10.1007/s12031-026-02599-6","DOIUrl":"10.1007/s12031-026-02599-6","url":null,"abstract":"<div><p>Peripheral facial palsy (PFP) is a common neurological disorder. Acupuncture is an effective therapeutic intervention, yet its underlying molecular mechanisms remain incompletely elucidated. To evaluate the clinical efficacy of acupuncture for PFP and to identify differentially expressed RNAs and associated pathways via whole transcriptome analysis, thereby revealing potential molecular mechanisms. Clinical efficacy was assessed using the House-Brackmann (HB) scale, Facial Disability Index (FDI), and comprehensive traditional Chinese medicine efficacy criteria. Peripheral blood samples were collected from patients before and after acupuncture treatment. Differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs were screened through whole transcriptome sequencing. Bioinformatics analyses were employed to construct a competing endogenous RNA (ceRNA) network and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Acupuncture significantly improved clinical scores post-treatment. A total of 1625 differentially expressed mRNAs (1153 up-, 472 down-regulated), 715 lncRNAs (321 up-, 394 down-regulated), 85 circRNAs (56 up-, 29 down-regulated), and 253 miRNAs (141 up-, 112 down-regulated) were identified. The ceRNA network revealed that non-coding RNAs competitively bind key miRNA molecules, forming two distinct and independent regulatory axes that precisely modulate downstream target genes. KEGG enrichment analysis of core molecular targets indicated significant involvement in the Olfactory transduction and JAK-STAT signaling pathways. Acupuncture may exert its therapeutic effect on PFP by modulating the ceRNA network, alongside the Olfactory transduction and JAK-STAT signaling pathways, synergistically promoting nerve regeneration and suppressing neuroinflammation.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164796","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":"Mitoxyperiosis Defines a Monocyte-driven Inflammatory Endotype in Ischemic Stroke: Multi-cohort Transcriptomic and Single-cell CITE-seq Analysis","authors":"Xiao-kang Wang,&nbsp;De-kang Li,&nbsp;Bao-shu Wang,&nbsp;Jie He,&nbsp;Xiao-jia Wang","doi":"10.1007/s12031-026-02605-x","DOIUrl":"10.1007/s12031-026-02605-x","url":null,"abstract":"<div><p>Mitoxyperiosis is a recently identified form of regulated cell death driven by mitochondrial oxidative membrane rupture, but its role in ischemic stroke remains unknown. We investigated whether mitoxyperiosis-associated transcriptional activity identifies an inflammatory endotype and computationally prioritized candidate regulators. We analyzed peripheral-blood transcriptomes from GSE16561 (39 patients, 24 controls). Molecular subtypes were evaluated in GSE37587 (34 patients with paired Baseline and Follow-Up samples) and GSE58294 (23 patients sampled at 3, 5, and 24 h). CITE-seq data from GSE285659 (74,714 cells) were used for cellular localization. After adjustment for age and sex, 11 of 38 mitoxyperiosis-related genes were upregulated in ischemic stroke, and the pathway score was higher than in controls (<i>P</i> = 0.038; unadjusted Cohen's <i>d</i> = 0.80). Consensus clustering identified Mito-high (<i>n</i> = 12) and Mito-low (<i>n</i> = 27) subtypes (<i>d</i> = 2.51). Mito-high showed higher pyroptosis, ferroptosis, and necroptosis signature scores and lower expression of 11 of 12 differentially expressed immune checkpoints. All 50 subtype-associated genes were directionally concordant in GSE37587. In GSE58294, the inter-subtype effect size increased from 3 to 24 h (<i>d</i> = 0.83 to 1.20). Mito-high cells comprised 0.32% of profiled cells, of which 92.8% were monocytes. Connectivity mapping and target-pathway correlation analyses prioritized EZH2 and HDAC2 as candidate regulators. Mitoxyperiosis-associated transcriptional activity characterizes a monocyte-enriched inflammatory endotype in ischemic stroke. The Mito-high/Mito-low classification provides a molecular framework for investigating subtype-associated immune features and candidate epigenetic regulators.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126313","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":"Additive Enhancement of Neurovascular Regeneration and Functional Recovery by Combined MSC-Exosomes and Low-Intensity Pulsed Ultrasound in Ischemic Stroke Rats","authors":"Tiefeng Li,&nbsp;Shuyu Lyu,&nbsp;Xinyu Yao,&nbsp;Ting Xia,&nbsp;Zuojun Geng,&nbsp;Defeng Liu,&nbsp;Huiling Yi,&nbsp;Jiecong Zhang,&nbsp;Ao Zhang,&nbsp;Qi Wang,&nbsp;Lanxiang Liu","doi":"10.1007/s12031-026-02591-0","DOIUrl":"10.1007/s12031-026-02591-0","url":null,"abstract":"<div><p>Cerebral ischemic stroke (CIS) leads to high mortality and disability due to cerebrovascular obstruction. Current therapeutic approaches such as thrombolysis have limitations, and many patients suffer from long-term functional impairments, so new treatment strategies are urgently needed. Both low-intensity pulsed ultrasound (LIPUS) and mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated some therapeutic potential for CIS, but their efficacy is less pronounced when used alone. Therefore, this study aims to evaluate whether the combination of MSC-EXOs and LIPUS exerts an additive effect in the treatment of cerebral ischemic stroke. Adult rats subjected to middle cerebral artery occlusion (MCAO) were randomly assigned to sham, MCAO, MSC-EXO, LIPUS, or combination groups. Outcomes were assessed using the modified Neurological Severity Score (mNSS), corner and Y-maze tests, histological staining (HE and immunofluorescence), transmission electron microscopy (TEM), and quantitative real-time polymerase chain reaction (q-PCR). The combination group showed notable improvements in neurological function, with the highest proportion of cluster of differentiation 31 (CD31)/alpha-smooth muscle actin (α-SMA)/doublecortin (DCX)-positive immunofluorescence area, up-regulation of circular RNA SCMH-1(circSCMH-1), and the best restoration of synaptic ultrastructure. Compared with MSC-EXOs or LIPUS alone, the combined treatment appeared to have an additive effect, supporting neurovascular regeneration and functional recovery after cerebral ischemic stroke.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102502","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":"Collagen Triple Helix Repeat Containing 1 (CTHRC1) in the Nervous System: Expression, Signaling Mechanisms, and Functional Implications","authors":"Yingying Lei,&nbsp;Yuxi Luo,&nbsp;Ling Li","doi":"10.1007/s12031-026-02607-9","DOIUrl":"10.1007/s12031-026-02607-9","url":null,"abstract":"<div><p>Collagen triple helix repeat containing 1 (CTHRC1) is a secreted extracellular matrix (ECM)-associated protein involved in tissue remodeling, fibrosis, and cancer, but its functions in the nervous system remain incompletely defined. Evidence from peripheral nerve, brain tumor, neurodegeneration, and regeneration models suggests that CTHRC1 may exert context-dependent effects across neural and stromal cell populations. In Schwann cells, CTHRC1 regulates proliferation, migration, and the timing of myelination, whereas in glioma it promotes invasive behavior and treatment-resistant phenotypes. Human cortical proteomics, mouse-model studies, systems genetics, and a neuronal cell model associate CTHRC1 with Alzheimer’s disease-related phenotypes, although bulk tissue does not identify the cellular source and a small cerebrospinal fluid cohort showed no significant change. Temporally resolved single-cell analysis in zebrafish identified a transient <i>cthrc1a</i>-expressing fibroblast state required for coordinated inflammatory dynamics during regeneration; an equivalent mammalian mechanism has not been established. Evidence connecting CTHRC1 to synaptic regulation, neuroprotection, Parkinson’s disease, and cerebrovascular repair is still preliminary. Wnt, TGF-β/Smad, PI3K/AKT, and MAPK/ERK pathways provide candidate mechanisms, but many were characterized outside normal neural cells. This review critically evaluates the evidence by model and cell type and discusses biomarker and therapeutic prospects, including delivery, specificity, and safety constraints.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102565","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":"Bisphenol A Exposure Perturbs the Immune Microenvironment in Alzheimer’s Disease: Insights from Network Toxicology and Single-Cell Transcriptomics","authors":"Jinpu Wu,&nbsp;Yitong Wang,&nbsp;Ming Zhao,&nbsp;Jian Liu,&nbsp;Weimin Zhao","doi":"10.1007/s12031-026-02606-w","DOIUrl":"10.1007/s12031-026-02606-w","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder in which exposure to environmental endocrine-disrupting chemicals may contribute to disease susceptibility. Here, we integrated network toxicology, bulk transcriptomics, machine learning, immune deconvolution, single-nucleus transcriptomics, competing endogenous RNA (ceRNA) analysis, molecular docking, and 100-ns molecular dynamics (MD) simulations to investigate the potential molecular links between bisphenol A (BPA) exposure and AD. Cross-database integration identified 248 shared BPA-AD targets, from which 47 network-central genes and 19 differentially expressed genes were prioritized. Five genes-GSK3B, BCL2, EGFR, APP, and PPARD-were subsequently retained as a candidate gene signature. Although the resulting model showed strong discriminatory performance in the discovery cohort, substantially lower performance in validation cohorts indicated limited generalizability and potential overfitting. Functional analyses implicated neuroinflammatory signaling, mitochondrial apoptosis, amyloid-related processes, and lipid and metabolic dysregulation in the molecular association between BPA and AD. LM22-based CIBERSORT analysis revealed alterations in peripheral leukocyte-like immune signatures, which were interpreted cautiously because this reference matrix does not directly represent resident brain immune populations. Single-nucleus transcriptomic analysis of GSE163577 further localized key genes across biologically plausible cerebrovascular and neuroimmune cell populations. CeRNA analysis suggested potential post-transcriptional regulatory relationships associated with the identified hub genes, while molecular docking identified putative interactions between BPA and candidate target proteins. Subsequent 100-ns MD simulations further characterized the dynamic behavior and conformational stability of the selected BPA-protein complexes, providing complementary evidence for the docking-derived structural hypotheses. Collectively, these findings suggest that BPA-related molecular targets may converge on immune, vascular, metabolic, and neurodegenerative processes relevant to AD. However, the present findings remain primarily computational and hypothesis-generating, and experimental studies are required to establish causal and mechanistic relationships.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102538","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":"Ferroptosis–Pyroptosis Crosstalk in Spinal Cord Injury: Molecular Mechanisms, Emerging Connectors, and Staged Therapeutic Perspectives","authors":"Chen Wang,&nbsp;Ye Jin,&nbsp;Weihua Cai","doi":"10.1007/s12031-026-02604-y","DOIUrl":"10.1007/s12031-026-02604-y","url":null,"abstract":"<div><p>Secondary injury after spinal cord injury (SCI) develops through intertwined oxidative, metabolic and inflammatory processes that engage several programmes of regulated cell death. Ferroptosis and pyroptosis are both implicated in experimental SCI, but their relationship across cellular compartments and injury phases remains incompletely understood. Ferroptotic injury is prominent in neurons, oligodendrocyte-lineage cells and vascular endothelium. Inflammasome–gasdermin signalling is concentrated mainly in microglia and infiltrating myeloid cells. Their partial cellular separation raises the possibility that coupling occurs through shared lesion stress and communication between neighbouring populations. This review examines how metabolic, redox and inflammatory disturbances shape ferroptosis–pyroptosis coupling across cells and over time, and distinguishes common upstream regulation from direct cross-pathway control. The emerging picture is one of context-dependent metabolic–inflammatory coupling, with the strength and direction of interaction likely to vary across lesion compartments and injury phases. Clinical translation will depend on identifying where and when each pathway is active and on developing biomarkers and treatment strategies matched to lesion biology.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029449","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":"ABCC9/SUR2 has a Complex Expression Pattern in Human Brain Gliovascular Unit Cells, Including Astrocytes","authors":"Yuriko Katsumata,&nbsp;Josh M. Morganti,&nbsp;Andrew Liao,&nbsp;Wei Zhou,&nbsp;Yu Zhong,&nbsp;Shuling Fister,&nbsp;Kai Saito,&nbsp;Qi Qiao,&nbsp;Sergei Artiushin,&nbsp;Angela Wei,&nbsp;Gao Jian,&nbsp;Colin G. Nichols,&nbsp;Tiffany L. Lee,&nbsp;Dana M. Niedowicz,&nbsp;Ryan K. Shahidehpour,&nbsp;Christopher M. Norris,&nbsp;Colin B. Rogers,&nbsp;David W. Fardo,&nbsp;Junyue Cao,&nbsp;Peter T. Nelson","doi":"10.1007/s12031-026-02603-z","DOIUrl":"10.1007/s12031-026-02603-z","url":null,"abstract":"<div><p>The <i>ABCC9</i> gene and its cognate protein SUR2 play important roles in neurovascular coupling and are implicated in hippocampal sclerosis of aging (HS-Aging). However, prior studies have not focused on human brain SUR2 expression or SUR2 in glial cells. Here we analyzed cell type-specific <i>ABCC9</i>/SUR2 expression patterns, and correlation with known genetic risk variants, using multiple data sets and a novel antiserum. Existing single-nucleus RNA sequencing data sets and new spatial transcriptomics data indicated that <i>SUR2</i> transcripts were expressed primarily in human brain pericytes, astrocytes, smooth muscle cells, and endothelial cells. Evaluation of <i>Sur2</i> expression in a sample of mice brains showed similar results except <i>Sur2</i> was not detected in the mice astrocytes. In a <i>SUR2</i>-enriched subcluster of human astrocytes, the pattern of transcript expression suggested responsiveness to thyroid hormone signaling: <i>SUR2</i>-correlated gene products were enriched for thyroid hormone-sensitive transcripts and <i>SLCO1C1</i>, the astrocyte thyroid hormone importer, was the transcript with the strongest correlation with <i>SUR2</i> expression. Cells in the SUR2 + astrocyte cluster tended to have been derived from individuals lacking severe Alzheimer’s disease pathology. An <i>ABCC9</i> single nucleotide variant (rs1914361, also a HS-Aging risk allele) was associated with increased <i>SUR2</i> expression in astrocytes, but not other cell types. <i>SUR2</i> mRNA splicing differed between cell types; astrocytes preferentially expressed the <i>SUR2B</i> variant. A novel SUR2 antiserum immunolabeled blood vessel walls and some astrocyte-morphology cells in human brain. Overall, human brain <i>SUR2</i> expression was enriched among different cell types of the gliovascular unit. A <i>SUR2</i>-enriched, possibly-homeostatic astrocyte subcluster suggested connections to thyroid hormone signaling.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-026-02603-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986960","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}