Frontiers in Cellular Neuroscience最新文献

{"title":"(Ba,Ca)(Ti,Sn)O₃-based piezoelectric ceramics promotes neuroprotection by regulating microglial IL-6/JAK2/STAT3 signaling pathway.","authors":"Haiwang Song, Geng Tang, Yumei Li, Baofei Sun, Zijiang Yu, Mudan Zhang, Dan Yang","doi":"10.3389/fncel.2026.1793008","DOIUrl":"https://doi.org/10.3389/fncel.2026.1793008","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether (Ba,Ca)(Ti,Sn)O₃-based piezoelectric ceramics (BCTS) provide neuroprotection by inhibiting the IL-6/JAK2/STAT3 signaling pathway in microglia.</p><p><strong>Methods: </strong>BCTS surface morphology and elemental distribution were analyzed using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDX), phase composition was determined via X-ray diffraction (XRD), and hydrophilicity was measured through contact angle analysis. Immunofluorescence (IF), Western blot, and ELISA were employed to evaluate the expression of microglial markers and inflammatory factors in the BV2 injury model and in spinal cord injury rats. Behavioral tests were conducted to evaluate motor function recovery in spinal cord injury rats. PC12 cells were cultured with BCTS-CM (supernatant from BCTS-treated BV2 cells) to assess the IL-6/JAK2/STAT3 signaling pathway expression and its effects on LDH release, antioxidant enzyme activity, apoptotic proteins, and β-III-tubulin expression.</p><p><strong>Results: </strong>BCTS exhibited a pure perovskite phase, densely packed grains, and favorable hydrophilicity. It did not affect BV2 cell viability but inhibited LPS-induced M1 microglial activation, reducing the expression of TNF-α, IL-1β, and IL-6. Simultaneously, BCTS promoted M2 microglial polarization, upregulating IL-4, IL-10, and TGF-β1. In PC12 cells, BCTS-CM increased cell survival, antioxidant activities, Bcl-2, and β-III-tubulin expression, while decreasing LDH release, MDA content, BAX and Cleaved Caspase-3 expression. BCTS-induced neuroprotection is mediated by the suppression of the IL-6/JAK2/STAT3 signaling pathway, as evidenced by the fact that IL-6 supplementation counteracts this protection while AG490 treatment further reinforces it compared to BCTS-CM alone. In the spinal cord injury rat model, BCTS inhibited the expression of microglia and inflammatory factors at the injury site, while improving the BBB score and reducing the error rate in the grid walking test.</p><p><strong>Conclusion: </strong>(Ba,Ca)(Ti,Sn)O₃-based piezoelectric ceramics exhibit neuroprotective effects by inhibiting IL-6 secretion from microglia, thereby preventing the activation of the IL-6/JAK2/STAT3 signaling pathway in neurons.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1793008"},"PeriodicalIF":4.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Long non-coding RNA TUSC7, a target of miR-23b, plays tumor-suppressing roles in human gliomas.","authors":"","doi":"10.3389/fncel.2026.1834443","DOIUrl":"https://doi.org/10.3389/fncel.2026.1834443","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fncel.2016.00235.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1834443"},"PeriodicalIF":4.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired myelination in multiple sclerosis organoids: p21 links oligodendrocyte dysfunction to disease subtype.","authors":"Saud A Sadiq, Tanmay Mehta, William Holzman, Annie McDermott, Nicolas Daviaud","doi":"10.3389/fncel.2026.1786186","DOIUrl":"https://doi.org/10.3389/fncel.2026.1786186","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are strongly involved in its pathogenesis. We derived cerebral and spinal cord organoids from induced pluripotent stem cells (iPSC) from healthy controls as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients to investigate and compare oligodendrocyte differentiation and myelination capacity. In MS organoids, particularly in PPMS, we observed a decrease in p21 expression associated with a dysregulation of PAK1 and E2F1 expression. In parallel, a decrease in oligodendrocyte maturation was detected in long-term cultured cerebral and spinal cord organoids, especially in PPMS, leading to a reduced myelination capacity. Disruption of astrocyte and neuronal populations was also observed. Our findings demonstrate that in MS, inherent deficits in the p21 pathway may alter glial and neuronal cell populations and may contribute to the disease pathogenesis by reducing the capacity for myelin repair.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1786186"},"PeriodicalIF":4.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etifoxine drives macrophage M2 polarization via Schwann cell-derived progesterone activation of PPARγ to accelerate peripheral nerve repair.","authors":"Chao Guo, Song Liu","doi":"10.3389/fncel.2026.1789450","DOIUrl":"https://doi.org/10.3389/fncel.2026.1789450","url":null,"abstract":"<p><strong>Background: </strong>Peripheral nerve injury (PNI) presents a significant clinical challenge due to limited endogenous regenerative capacity. The translocator protein (TSPO) ligand etifoxine (ETX) has shown promise in promoting nerve repair, but the underlying cellular and molecular mechanisms remain incompletely understood.</p><p><strong>Methods: </strong>Utilizing in vitro co-culture systems with human Schwann cells (HSCs) and THP-1-derived macrophages, TSPO-knockdown HSCs, conditioned medium experiments, and an in vivo rat sciatic nerve crush injury model, we investigated the effects of ETX on cellular crosstalk and macrophage polarization. Molecular analyses included RNA sequencing, western blotting, fatty acid oxidation (FAO) assays, and a Mito-QC reporter system to assess mitophagy. Functional recovery was evaluated through behavioral tests (hindlimb grip strength, mechanical pain threshold), immunofluorescence, and retrograde tracing.</p><p><strong>Results: </strong>ETX specifically activated TSPO on Schwann cells, stimulating progesterone synthesis and secretion. This Schwann cell-derived progesterone acted as a paracrine signal on macrophages, activating the PPARγ-PGC1α axis. This activation triggered dual reprogramming in macrophages: a metabolic shift toward FAO and induction of BNIP3L-mediated mitophagy, both essential for sustaining a pro-regenerative M2 phenotype. These effects were significantly attenuated by the progesterone receptor antagonist RU486 or the PPARγ antagonist GW9662. In vivo, ETX treatment accelerated functional recovery, enhanced axonal regeneration, and increased infiltration of M2 macrophages at the injury site, effects that were partially reversed by RU486 or GW9662 co-administration.</p><p><strong>Conclusion: </strong>ETX facilitates peripheral nerve repair by promoting Schwann cell-derived progesterone, which drives macrophage PPARγ pathway activation, orchestrating metabolic-autophagic reprogramming necessary for sustained M2 polarization. These findings identify a novel Schwann cell-macrophage metabolic crosstalk mechanism and support the therapeutic potential of targeting this axis in PNI.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1789450"},"PeriodicalIF":4.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13060035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stochasticity in action potential backpropagation: consequences for neuronal computation.","authors":"Srdjan D Antic, Katarina D Milicevic, William W Lytton","doi":"10.3389/fncel.2026.1803262","DOIUrl":"https://doi.org/10.3389/fncel.2026.1803262","url":null,"abstract":"<p><p>In cortical and hippocampal pyramidal neurons, backpropagating action potentials (bAPs) play a central role in dendritic signaling, synaptic integration, and spike-timing-dependent plasticity (STDP). In most experimental and theoretical frameworks, bAPs are implicitly treated as reliable signals that faithfully inform dendritic synapses of somatic spiking. Here, we review experimental evidence demonstrating that this assumption is often violated. In large portions of the pyramidal neuron dendritic tree, particularly in distal apical branches and apical tuft dendrites, bAP amplitude exhibits pronounced spatial and temporal variability, including: (i) activity-dependent attenuation, (ii) frequency-dependent amplification, (iii) branch-specific propagation failures, and (iv) trial-to-trial stochastic AP flickering. We summarize five experimentally documented forms of bAP variability and discuss how stochastic backpropagation may shape synaptic plasticity in computational neuroscience, especially STDP, by introducing probabilistic gates that limit the coincidence of: (i) dendritic depolarization (bAP) and (ii) synaptic input (EPSP). Finally, we consider broader implications of the AP flickering in dendrites for cortical information processing, including redundancy, averaging, evidence accumulation, and error-correcting strategies in cortical circuits.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1803262"},"PeriodicalIF":4.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-19a-3p and miR-19b-3p repress Nurr1 and Nur77 to promote microglial inflammation after spinal cord injury.","authors":"Faezeh Sahebdel, Aliabbas Zia, Hector Ramiro Quintá, Andres Stucky, Leslie R Morse, Julie K Olson, Ricardo A Battaglino","doi":"10.3389/fncel.2026.1783899","DOIUrl":"https://doi.org/10.3389/fncel.2026.1783899","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI)-induced neuropathic pain affects up to 60% of individuals with SCI and is closely linked to microglia-driven neuroinflammation. Neuroinflammatory processes after SCI are major contributors to the development and persistence of chronic pain. MicroRNAs (miRNAs) have emerged as regulators of neuroinflammation. There are higher levels of circulating miR-19a and miR-19b in persons living with SCI with neuropathic pain compared to those with no pain. These miRNAs are associated with altered the neuroprotective genes Nurr1 and Nur77.</p><p><strong>Methods: </strong>Primary microglia cultures and a rat spinal cord injury model were used to investigate the regulatory effects of miR-19a and miR-19b on Nurr1 and Nur77 expression.</p><p><strong>Results: </strong>Our study shows that miR-19a and miR-19b and their binding sites in Nurr1's 3' UTR are highly conserved across vertebrates, suggesting functional importance. Through <i>in vitro</i> microglia cultures and <i>in vivo</i> rat SCI models, we demonstrate that these miRNAs negatively regulate Nurr1, Nur77, and inflammatory gene expression. Protein-protein interaction network analysis highlights transcription factors such as MYC, RUNX1, and STAT3 as central to this regulatory network.</p><p><strong>Conclusion: </strong>These findings support a model in which miR-19a and miR-19b contribute to microglia-driven neuroinflammation after SCI and highlight their potential as therapeutic targets to reduce neuropathic pain.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1783899"},"PeriodicalIF":4.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum NfL and GFAP in post-COVID syndrome: minimal evidence of CNS injury after adjusting for confounders.","authors":"Michael Wunderle, Andrea Ribeiro, Isabelle Lethen, Rebecca Wicklein, Emily Feneberg, Anna Wöhnl, Johanna Negele, Veronika Kesseler, Samuel Niedermayer, Maciej Lech, Timon Wallraven, Christoph Schmaderer","doi":"10.3389/fncel.2026.1750121","DOIUrl":"https://doi.org/10.3389/fncel.2026.1750121","url":null,"abstract":"<p><strong>Background: </strong>Post-COVID syndrome (PCS) often includes neurological symptoms, but evidence for persistent CNS injury remains inconsistent. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astroglial injury. We investigated whether serum NfL and GFAP differ between PCS patients and recovered controls after adjusting for age and renal function.</p><p><strong>Methods: </strong>In this prospective single-center case-control study, serum NfL and GFAP were quantified using Simoa® (Quanterix) in 102 PCS patients and 102 recovered controls. Group comparisons employed Mann-Whitney tests and ANCOVA-style multivariable linear regression of log-transformed biomarkers adjusted for age, sex, and eGFR. Associations with eGFR were examined in multivariable models, and findings were validated in an age- and sex-matched cohort.</p><p><strong>Results: </strong>Age emerged as the primary determinant of NfL and GFAP concentrations. The inverse correlations with renal function (NfL <i>ρ</i> = -0.23; GFAP <i>ρ</i> = -0.33) and the initially higher GFAP in PCS (60.4 vs. 52.3 pg/mL; <i>p</i> = 0.002) were largely explained by age. After adjustment for age, sex, and eGFR, neither biomarker showed independent differences between groups (adjusted GMRs: NfL 1.04 [0.91-1.18], <i>p</i> = 0.59; GFAP 1.10 [0.96-1.26], <i>p</i> = 0.15). In an age- and sex-matched cohort (71 pairs), adjusted analyses confirmed no difference in NfL (<i>p</i> = 0.48), while GFAP demonstrated a significant increase in PCS (<i>β</i> = 0.15, <i>p</i> = 0.025).</p><p><strong>Conclusion: </strong>GFAP concentrations were modestly elevated in PCS in an age- and sex-matched cohort and persisted after adjustment for kidney function, whereas NfL showed no group differences. These findings argue against widespread neuroaxonal injury in PCS and suggest only a subtle astroglial signal in a subset of patients. Rigorous adjustment for confounders-particularly age, sex, and renal function-is essential for valid interpretation of serum neuroinjury biomarkers in PCS.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1750121"},"PeriodicalIF":4.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13046514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-spinal cord barrier disruption after spinal cord injury: a time-dependent mechanistic review.","authors":"Zhirui Jiang, Ce Zhang, Zejing Zhao, Bin Ning","doi":"10.3389/fncel.2026.1805529","DOIUrl":"https://doi.org/10.3389/fncel.2026.1805529","url":null,"abstract":"<p><p>The blood-spinal cord barrier (BSCB) is a specialized vascular interface that preserves spinal cord homeostasis by regulating molecular and cellular trafficking between blood and neural tissue. Disruption of BSCB integrity is a critical pathological event follow-ing spinal cord injury (SCI), leading to increased permeability, inflammatory cell infil-tration, and secondary neurodegeneration. Increasing evidence indicates that BSCB breakdown is not a single event but a dynamic, time-dependent process. In this review, we summarize the molecular and cellular mechanisms responsible for BSCB disruption after SCI in a chronological manner. Key pathological events occurring during the acute, subacute, and chronic phases are discussed, including pathological hemody-namic changes, endothelial stress responses, epigenetic regulation, inflammatory me-diators, immune cell-endothelial interactions, and extracellular matrix remodeling. We further highlight endogenous protective and reparative mechanisms that emerge at later stages. A comprehensive understanding of the temporal characteristics of BSCB disruption may facilitate the development of phase-specific therapeutic strate-gies aimed at preserving barrier integrity, limiting secondary injury, and improving neurological recovery after SCI. This temporal perspective underscores the need for stage-specific interventions to preserve BSCB integrity and improve outcomes after SCI.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1805529"},"PeriodicalIF":4.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic signatures in tetrapartite brain region identifies shared and unique gene signatures for substance-use.","authors":"Avinash Veerappa, Chittibabu Guda","doi":"10.3389/fncel.2026.1770214","DOIUrl":"https://doi.org/10.3389/fncel.2026.1770214","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic substance use is a neuropsychiatric disorder marked by persistent craving, reward seeking, and progression to addiction. The midbrain governs hunger, reward, and pleasure; the DLPFC modulates craving, decision making, and tolerance; the NAc influences feeding, reward, stress, and drug self-administration; and the amygdala regulates emotion and memory.</p><p><strong>Methods: </strong>To understand these complex and dynamic events in the context of substance use disorders, we profiled transcriptomes from these four regions and integrated clustering, biclustering, WGCNA, and pathway enrichment analyses.</p><p><strong>Results: </strong>Upregulation of gene expression was dominant in all four brain regions of cases versus controls. Distinct differential transcriptomic signatures were both unique to individual regions and shared across regions, identifying 186 genes exclusive to midbrain, 29 to DLPFC, 160 to NAc, and 442 in amygdala. Network analysis revealed DEGs across all regions interconnected via a neuropeptide-neurotransmitter axis, suggesting substances disrupt the equilibrium between neurotransmitters and neuropeptides. Significant upregulation of CSF3, GADD45B, SOCS3, and NPAS4 across all four regions enriched the CREB Signaling in Neurons pathway, supporting their involvement in long-lasting maladaptations of neurocircuitry due to chronic substance use.</p><p><strong>Discussion: </strong>By unraveling unique and shared transcriptomic signatures, our study advances understanding of crosstalk among key players in each brain region in substance use, implying that induction and exclusion signals drive distinct pathway signaling and sustain addiction behavior. Alongside known genes in substance biology and addiction, we also identified several novel biomarkers that could confer susceptibility for addiction risk.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1770214"},"PeriodicalIF":4.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O-GlcNAc transferase controls excitatory synapse development and AMPA receptor expression in an activity-dependent manner.","authors":"Linkun Han, Olof Lagerlöf","doi":"10.3389/fncel.2026.1799487","DOIUrl":"https://doi.org/10.3389/fncel.2026.1799487","url":null,"abstract":"<p><p>Brain development and neural circuit function depend on the formation and termination of excitatory synapses. The regulation of excitatory synapse plasticity has long been associated with neuronal activity. In addition to neuronal activity, emerging data show that body metabolism affects synaptic plasticity. However, it is unclear how neuronal activity and metabolic signaling may interact to control the number and function of excitatory synapses. The nutrient sensor O-GlcNAc transferase (OGT), an enzyme that catalyzes O-GlcNAcylation of cytoplasmic and nuclear proteins depending on the metabolic state of the body, has been implicated in excitatory synapse maturation, but its activity-dependent roles and underlying mechanisms are unclear. Here, we investigated how OGT regulates excitatory synapse structure, number and AMPA-type glutamate receptors (AMPARs) in cultured hippocampal neurons under normal and activity-suppressed conditions. We show that OGT overexpression selectively enhances accumulation of the AMPARs subunit GluA1 in dendritic spines at a mature developmental stage (DIV14), but not during early development (DIV7). Chronic suppression of neuronal activity with tetrodotoxin (TTX) abolished the OGT-dependent increase in GluA1 expression, indicating that OGT-mediated regulation of AMPARs is activity-dependent. In parallel, OGT overexpression promoted coordinated growth and maturation of excitatory synapses, increasing the size and intensity of postsynaptic PSD-95 and presynaptic vGluT1 puncta, particularly at colocalized synaptic sites. These structural effects, as well as OGT-induced increases in excitatory synapse number, were eliminated by activity blockade. Together, our findings identify the nutrient sensor OGT as an activity-dependent regulator of excitatory synapse maturation and AMPARs accumulation, revealing a molecular mechanism by which neuronal activity and metabolic signaling can be integrated to shape synaptic connectivity and function.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1799487"},"PeriodicalIF":4.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}