Frontiers in Cellular Neuroscience最新文献

{"title":"Method for the simultaneous isolation of primary astrocytes and microglia from the neonatal rats cerebral cortex.","authors":"Kun Zhang, Songcan Wu, Yujie Zeng, Xinglin Wu, Meiming Qian, Kaya Xu","doi":"10.3389/fncel.2026.1787397","DOIUrl":"https://doi.org/10.3389/fncel.2026.1787397","url":null,"abstract":"<p><strong>Objective: </strong>To establish a protocol for the simultaneous isolation and high-purity purification of primary astrocytes and microglia from neonatal rats cerebral cortex.</p><p><strong>Methods: </strong>Single-cell suspensions were prepared from cerebral cortices of postnatal day 2 (P2) rat pups. Fibroblasts were pre-removed using differential adhesion techniques. Mixed glial cultures were maintained with graded serum (from 10% to 5% to 2% FBS) to suppress fibroblast proliferation. On day 14, microglia were isolated by constant temperature shaking (200 rpm, 12 h, 37 °C), followed by manual agitation of remaining adherent cells to purify astrocytes. Cell purity was assessed by immunofluorescence (Iba1 and GFAP) and validated by multicolor flow cytometry (CD11b/CD45; ACSA-2) and ER-TR7 fibroblast exclusion staining. Cell viability was evaluated by trypan blue exclusion and CCK-8 assay. Microglial morphology was quantified by cell body area, circularity index, and primary process number.</p><p><strong>Results: </strong>Day 14 was identified as the optimal separation time point. Immediately post-shaking, microglia purity (Iba1⁺) reached 98.6% ± 1.1%, and astrocyte purity (GFAP⁺) was 98.4% ± 1.7%. After subsequent purification culture, these values increased to 98.98% ± 1.21% and 98.81% ± 2.38%, respectively. Dual-label immunofluorescence confirmed minimal cross-contamination, with Iba1⁺/GFAP⁺ dual-positive cells constituting <1% in both populations. Multicolor flow cytometry corroborated these findings, yielding CD11b⁺ purity of 97.12% ± 1.58% for microglia (with 95.37% ± 1.84% classified as CD11b⁺/CD45^low homeostatic microglia) and ACSA-2⁺ purity of 94.65% ± 2.73% for astrocytes. No unequivocal ER-TR7⁺ fibroblasts were identified in either purified population. Microglial morphology progressively transitioned from amoeboid (Day 0: area 173.5 ± 32.8 μm²; circularity 0.847 ± 0.058; processes 0.8 ± 0.4) to ramified (Day 5: area 418.2 ± 68.3 μm²; circularity 0.438 ± 0.095; processes 4.3 ± 0.8 per cell). Cell viability remained above 92% following key procedural steps and recovered to over 95% post-purification; CCK-8 assay confirmed full metabolic recovery.</p><p><strong>Conclusion: </strong>This study establishes a combined method utilizing graded serum and constant temperature shaking for glial cell isolation, enabling simultaneous acquisition of both major glial cell types from a single animal. This cost-effective protocol provides a practical tool for functional studies of neuroglial cells.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1787397"},"PeriodicalIF":4.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835884","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":"Non-cell autonomous downregulation of the purinergic receptor P2Y1R promotes neuroprotection after ischemic injury.","authors":"Gabrielle Spagnuolo, Lorraine Iacovitti","doi":"10.3389/fncel.2026.1790325","DOIUrl":"https://doi.org/10.3389/fncel.2026.1790325","url":null,"abstract":"<p><p>Current ischemic stroke treatments largely focus on exogenous means of neural repair, with endogenous mechanisms being less understood. Here, we examine the cellular and molecular foundation of an endogenous neuroprotective mechanism using the <i>in vitro</i> stroke model oxygen-glucose deprivation (OGD). We demonstrate that after OGD, dying cortical neurons release ATP to activate microglia. There is a simultaneous increase in microglial release of B-NGF and IL-2, increased TrkA receptor expression on astrocytes, and a consequent downregulation in astrocyte P2Y1 receptors (P2Y1R), resulting in a decline in neuronal intracellular calcium levels and enhanced neuronal survival. This neuroprotective effect is mimicked when P2Y1R expression is directly knocked out in astrocytes or when exogenous microglial activators IL2 or NGF are added in place of microglia. Conversely, these neuroprotective effects are prevented by blockade of microglial activation or inhibition of TrkA or IL-2 receptors. Pharmacological buffering of intracellular Ca²⁺ with BAPTA-AM recapitulated the neuroprotective effect, whereas NMDA receptor blockade with Dizocilpine maleate did not, indicating that neuronal survival is mediated by reduced intracellular Ca²⁺ accumulation through an NMDA receptor-independent mechanism. Together, these results suggest the downregulation of P2Y1R in astrocytes by activated microglia is a critical endogenous neuroprotective mechanism after ischemic injury. By understanding these inherent non-cell autonomous mechanisms and their molecular mediators, it may be possible to improve intrinsic neuroprotection and recovery from stroke.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1790325"},"PeriodicalIF":4.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835888","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":"Editorial: Axon neurobiology: updates in functional and structural dynamics.","authors":"Haruyuki Kamiya, Dominique Debanne","doi":"10.3389/fncel.2026.1838278","DOIUrl":"https://doi.org/10.3389/fncel.2026.1838278","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1838278"},"PeriodicalIF":4.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812426","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":"Comprehensive 3D mapping reveals distinct spatial gradients of genetically-identified SST, PV, and TH interneurons across the mouse caudoputamen.","authors":"Jonibek M Muhsinov, Evan A Iliakis, Wenxin Tu, Alexandra N Ramirez, Michael A Muniak, Andrzej Z Wasilczuk, M Felicia Davatolhagh, Alex Proekt, Tianyi Mao, Marc Vincent Fuccillo","doi":"10.3389/fncel.2026.1795921","DOIUrl":"10.3389/fncel.2026.1795921","url":null,"abstract":"<p><strong>Introduction: </strong>In addition to spatially organized excitatory forebrain inputs along its mediolateral, dorsoventral, and anteroposterior axes, the dorsal striatum (caudoputamen) relies on cellular diversity to subserve its myriad processing functions. Distinct GABAergic interneuron subtypes, including somatostatin (SST), parvalbumin (PV), and tyrosine hydroxylase (TH) interneurons likely subserve complementary computational roles. However, a detailed understanding of how these microcircuit components are distributed across the caudoputamen remains lacking.</p><p><strong>Methods: </strong>To address this gap, we generated a comprehensive three-dimensional atlas of genetically-defined SST-, PV-, and TH- labeled interneuron populations across the mouse caudoputamen using genetic labeling, caudoputamen-wide imaging, and voxel-wise quantification.</p><p><strong>Results: </strong>We found that genetically-defined SST and TH interneurons were relatively enriched in the ventral caudoputamen, whereas PV interneurons were enriched dorsally. In addition, PV and TH interneurons exhibited opposing anteroposterior distribution patterns, with PV interneurons enriched posteriorly and TH interneurons showing a marked decline in density toward the tail of the caudoputamen. Consequently, while the three interneuron subtypes displayed comparable densities in the functionally defined lateral caudoputamen and anterior ventromedial caudoputamen, PV interneurons predominated in the dorsomedial caudoputamen and tail of the caudoputamen. While some statistically significant sex differences were detected, the overall spatial distribution patterns of interneurons were similar across sexes.</p><p><strong>Discussion: </strong>Together, these findings reinforce the view that the caudoputamen is not a monolithic structure: in addition to excitatory and neuromodulatory inputs, inhibitory microcircuits themselves are differentially distributed across the caudoputamen, providing region-specific constraints on circuit computation. By integrating interneuron organization into existing anatomical frameworks, this atlas provides a foundation for linking dorsal striatal anatomy to function across behavioral domains.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1795921"},"PeriodicalIF":4.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812039","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":"Cocaine remodels m⁶A RNA-dependent signaling to drive locomotor plasticity in <i>Drosophila melanogaster</i>.","authors":"Ana Filošević Vujnović, Nina Milotić, Bobana Samardžija, Marko Rubinić, Rozi Andretić Waldowski, Alessia Soldano","doi":"10.3389/fncel.2026.1810118","DOIUrl":"https://doi.org/10.3389/fncel.2026.1810118","url":null,"abstract":"<p><p>N⁶-methyladenosine (m⁶A) is a dynamic RNA modification that regulates RNA stability, processing, and translation and is increasingly recognized as a key modulator of neuronal plasticity. However, how psychostimulant exposure reshapes m⁶A-dependent regulatory networks across coding and non-coding RNA species remains poorly understood. We investigated the impact of volatilized cocaine (vCOC) exposure on m⁶A RNA methylation, m⁶A pathway components, transcriptome, and cocaine-induced locomotor sensitization in <i>Drosophila melanogaster</i>. Acute vCOC administration significantly increased global m⁶A levels in total and poly(A)-enriched RNA, with a stronger effect in polyadenylated transcripts. This increase occurred without changes in the m⁶A methyltransferases Mettl3 and Mettl14 transcripts, but was accompanied by robust upregulation of the levels of m⁶A reader YTHDC and YTHDF transcripts. Genetic and cell-type-specific analyses revealed distinct and context-dependent roles for m⁶A writers and readers in neurons and glia, with m⁶A readers being essential for vCOC-induced locomotor sensitization. Integration of RNA-seq and MeRIP-seq demonstrated that vCOC selectively amplifies m⁶A modification of regulatory and plasticity-associated RNA classes, including mRNAs involved in RNA processing, antisense RNAs, long non-coding RNAs, and transposable element-derived transcripts. In contrast, m⁶A-modified RNAs shared in CTRL and vCOC were enriched for core metabolic and mitochondrial pathways, such as oxidative phosphorylation. Notably, vCOC increased m⁶A modification of non-coding RNAs and transposable elements with minimal overlap with control conditions, indicating cocaine-induced engagement of epitranscriptomic regulation at multiple layers of the transcriptome. Together, these findings reveal that cocaine exposure reinforces an m⁶A-defined regulatory RNA network, spanning coding and non-coding transcripts that is mechanistically linked to m⁶A reader-dependent behavioral plasticity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1810118"},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813041","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":"Structure matters: commensal <i>Phocaeicola vulgatus</i> lipopolysaccharide induces attenuated microglial activation and preserves neuronal integrity.","authors":"Valentina Mazziotti, Luca De Simone Carone, Francesca Olmeo, Fabrizio Chiodo, Alba Silipo, Antonio Molinaro, Flaviana Di Lorenzo","doi":"10.3389/fncel.2026.1796397","DOIUrl":"https://doi.org/10.3389/fncel.2026.1796397","url":null,"abstract":"<p><p>Lipopolysaccharides (LPSs) from Gram-negative bacteria are widely used to model neuroinflammation <i>in vitro</i> and <i>in vivo</i>. However, this paradigm assumes that all LPS chemotypes are uniformly pro-inflammatory, despite significant structural diversity between enterobacterial pathogens and gut-resident commensals. Whether microglia can discriminate among these chemotypes remains largely unexplored. We performed a comparative analysis of canonical <i>Escherichia coli</i> LPS and commensal-derived <i>Phocaeicola vulgatus</i> LPS in murine (BV2) and human (HMC3) microglial cells. Pro-inflammatory mediators were quantified by ELISA, and TLR4-downstream signaling was assessed by western blotting. Conditioned media (CM) from LPS-treated BV2 and HMC3 cells was applied to PC12 neuronal cells to evaluate cell viability and differentiation by immunofluorescence. In BV2 microglial cells, <i>P. vulgatus</i> LPS did not induce nitric oxide (NO) production or iNOS expression. In both BV2 and HMC3 cells, it failed to trigger pro-inflammatory cytokine release or TLR4 pathway activation. CM from <i>E. coli</i>-treated microglia disrupted MAP2 expression in PC12 neurons, whereas media from <i>P. vulgatus</i>-treated microglia did not. Overall, our data argue that \"LPS-induced neuroinflammation\" is not a universal phenomenon, but a chemistry-dependent outcome shaped by specific LPS structures. This study therefore highlights the need to consider LPS structural diversity in neuroinflammation models, particularly in the context of gut-brain communication.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1796397"},"PeriodicalIF":4.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767194","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":"Editorial: Reviews in cellular neuropathology.","authors":"Alessandro Tozzi, Chao Deng, Dirk M Hermann","doi":"10.3389/fncel.2026.1821476","DOIUrl":"https://doi.org/10.3389/fncel.2026.1821476","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1821476"},"PeriodicalIF":4.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767159","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":"Purkinje cell-specific loss of Neurofascin and Ankyrin G causes disruption of axon initial segments, neurodegeneration, and cerebellar ataxia.","authors":"Qian Shi, Anna M Taylor, Lacey B Sell, Manzoor A Bhat","doi":"10.3389/fncel.2026.1690466","DOIUrl":"https://doi.org/10.3389/fncel.2026.1690466","url":null,"abstract":"<p><p>The axon initial segment (AIS) is essential for initiating action potentials and maintaining neuronal polarity, yet the developmental roles of its core molecular components-Neurofascin 186 (NF186) and Ankyrin G (AnkG)-remain incompletely defined in cerebellar Purkinje cells. Here, we generated Purkinje cell-specific NF186 and AnkG single- and double-knockout mice to investigate how these adhesion and scaffolding proteins cooperatively regulate AIS formation, ion channel localization, synaptic targeting, and neuronal survival. We found that genetic ablation of either <i>Nfasc NF186</i> (<i>NFKO</i>) or <i>Ankyrin3</i> (<i>AnkGKO</i>) disrupted assembly and maintenance of the AIS cytoskeleton, and that this defect was exacerbated by combined loss of both proteins during postnatal development. Other AIS-enriched proteins, including βIV Spectrin (βIVSpec), voltage-gated sodium (Na_v), and potassium (K_v1.2) channels, failed to properly localize to the AIS and progressively disintegrated between postnatal days 10 and 30. Notably, K_v1.2 clustering at the pinceau synapse was disrupted, and basket cell axons showed misaligned terminal organization, indicating defective inhibitory synapse innervation. By 2 months of age, degeneration of Purkinje cells was evident, accompanied by cerebellar dysfunction. Notably, <i>AnkG</i> ablation caused a progressive postnatal loss of NF186 at the AIS, whereas <i>NF</i> ablation resulted in much slower loss of AnkG at the AIS in Purkinje cells and closely phenocopied the severe AIS destabilization observed in <i>NF/AnkG</i> double-knockout mice. In addition, our RNA-seq analysis revealed that Purkinje cell-specific loss of NF186 predominantly activated immune-inflammatory pathways; AnkG loss significantly disrupted neuronal developmental and metabolic processes; and the dual loss of NF186/AnkG produced transcriptional changes that were distinct from, and in part intermediate to, those observed in NF186 and AnkG single knockout. Collectively, our results show that NF186 and AnkG have complementary, non-redundant roles in establishing and maintaining the Purkinje cell AIS, and that their loss disrupts synaptic organization at the AIS. These findings advance our understanding of AIS development in cerebellar neurons and have implications for diseases involving AIS dysfunction, including cerebellar ataxia and demyelinating neuropathies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1690466"},"PeriodicalIF":4.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767203","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":"Sexual dimorphism and acute stress modulation of infralimbic-posterior hypothalamic synaptic transmission.","authors":"Yesenia Rivera-Escobales, Danisha N Hernández-Crispín, Jaileene Pérez-Morales, María Colón, James T Porter","doi":"10.3389/fncel.2026.1659293","DOIUrl":"https://doi.org/10.3389/fncel.2026.1659293","url":null,"abstract":"<p><p>Acute stress engages neural circuits that coordinate autonomic and neuroendocrine responses, including projections from the infralimbic cortex (IL) to the posterior hypothalamic nucleus (PH). Although both regions are activated during stress, the synaptic mechanisms underlying IL-to-PH communication remain poorly understood. Here, we combined optogenetics with whole-cell patch-clamp electrophysiology to determine how acute restraint stress alters excitatory synaptic transmission from IL to PH neurons in adult male and female rats. IL afferents formed functional glutamatergic synapses onto PH neurons in both sexes, characterized by short-term facilitation and a high AMPA/NMDA ratio. However, females exhibited smaller optically evoked excitatory postsynaptic currents (EPSCs) in response to single or burst stimulation across multiple holding potentials. NMDA receptor-mediated EPSCs and NMDAR-predominant spontaneous EPSCs also displayed sex differences, with females showing smaller and faster synaptic currents. When data were collapsed across sex, acute restraint stress enhanced NMDAR-mediated synaptic currents at IL-to-PH synapses while reducing the amplitude of NMDAR-predominant spontaneous EPSCs without altering their frequency. Together, these findings reveal sex-dependent differences in excitatory IL-to-PH synaptic signaling and suggest that acute stress preferentially modulates NMDAR-mediated transmission in this pathway. These results highlight dynamic postsynaptic mechanisms that shape prefrontal-hypothalamic communication during acute stress.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1659293"},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767154","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":"Cynanchum bungei Decne-derived extracellular vesicles alleviate cognitive impairment and pathological damage in Alzheimer's disease.","authors":"Rui Hong, Jingjing Han, Fuxing Dong, Umm-E Kalsoom, Cong Cao, Aihua Zhou, Qin Wu, Xuebin Qu","doi":"10.3389/fncel.2026.1798965","DOIUrl":"https://doi.org/10.3389/fncel.2026.1798965","url":null,"abstract":"<p><strong>Introduction: </strong><i>Cynanchum bungei</i> Decne (CB) is known for its therapeutic benefits for neurodegenerative conditions as anti-inflammatory, antioxidant, and barrier significantly limits their potential advantages. Given the ability of crossing the barrier with minimal toxicity, extracellular vesicles derived from CB (CB-EVs) were utilized as an innovative approach to mitigate Alzheimer's disease (AD).</p><p><strong>Methods: </strong>CB-EVs were isolated using gradient ultracentrifugation and identified via TEM imaging, nanoparticle tracking analysis, marker identification, and <i>in vivo</i> imaging system. Ten-month-old triple transgenic AD (3xTg-AD) mice received intravenous administration of CB-EVs at doses of 10 or 20 mg/kg every 3 days for the cognitive and pathological assessments. The human APP Swedish mutation transgenic SH-SY5Y cells were constructed as Aβ-induced neural damage model, and different concentrations of CB-EVs were added into medium to analyze its roles on cell viability, transcriptome changes, oxidative stress, and mitochondrial damage.</p><p><strong>Results: </strong>CB-EVs exhibited standard morphological and molecular traits, accumulating in the cerebral cortex and hippocampus. Two months of CB-EVs treatment alleviated cognitive impairments, diminished Aβ plaque, reduced Tau protein hyperphosphorylation, and lessened neuronal loss in 3xTg-AD mice. In transgenic SH-SY5Y cells, CB-EVs improved cell viability, enhanced superoxide dismutase activity, downregulated oxidative stress related NUPR1 and CHOP expression, decreased reactive oxygen species, lipid peroxidation, and malondialdehyde levels, reduced mitochondrial damage.</p><p><strong>Conclusion: </strong>These results demonstrated that CB-EVs could protect neurons from oxidative stress, attenuate cognitive impairment and pathological damage in AD.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1798965"},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767215","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}