Frontiers in Cellular Neuroscience最新文献

{"title":"Case Report: A case of paraneoplastic autoimmune encephalitis with concurrent anti-GABABR and anti-SOX1 antibody positivity.","authors":"Feng Liu, Ye-Han Jiang, Yu-Fang Hu, Jin-Guan Qin, Guang-Sheng Liu","doi":"10.3389/fncel.2026.1816167","DOIUrl":"10.3389/fncel.2026.1816167","url":null,"abstract":"<p><strong>Background: </strong>Paraneoplastic autoimmune encephalitis (PAE) is most commonly associated with small cell lung cancer (SCLC). Anti-<i>γ</i>-aminobutyric acid B receptor (GABABR) antibodies underlie a treatable limbic syndrome, whereas anti-SRY-box transcription factor 1 (SOX1) antibodies serve as high-specificity onconeural biomarkers of SCLC-driven autoimmunity. The sequential emergence of these two antibodies during the longitudinal course of a single patient has rarely been documented.</p><p><strong>Case presentation: </strong>A 75-year-old man presented with episodic impaired consciousness, behavioural disturbance and rapid cognitive decline. Brain MRI showed bilateral hippocampal signal abnormalities. A cell-based assay (CBA) detected anti-GABABR antibodies at high titre in serum (1:3200) and cerebrospinal fluid (CSF; 1:1000), while a tissue-based assay (TBA) on rat brain confirmed a neuronal cell-surface staining pattern; the full paraneoplastic panel, including anti-SOX1, was negative, and initial tumour screening was unrevealing. A diagnosis of anti-GABABR encephalitis (initially regarded as non-paraneoplastic) was made and the patient improved with intravenous immunoglobulin (IVIG), high-dose corticosteroids and maintenance mycophenolate mofetil. During a refractory second relapse 5 months later, repeat CBA showed rising anti-GABA_BR titres (serum 1:10,000; CSF 1:1000) and newly positive anti-SOX1 antibodies (serum 1:100; CSF 1:1); a previously occult right superior mediastinal mass radiologically compatible with SCLC was identified on repeat chest CT. The diagnosis was revised to anti-GABA_BR/anti-SOX1 dual-antibody PAE (probable PNS by 2021 PNS-Care criteria). The family declined biopsy, PET/CT and antitumour therapy because of advanced age and frailty; repeated IVIG with continued immunosuppression achieved partial clinical stabilisation with persistent cognitive impairment.</p><p><strong>Conclusion: </strong>Apparently isolated anti-GABA_BR encephalitis can evolve into dual anti-GABABR/anti-SOX1 paraneoplastic disease, with the second antibody heralding an occult SCLC. Repeating both CBA-based and intracellular antibody panels at every clinical relapse, together with repeat thoracic imaging, is essential to avoid missing an evolving paraneoplastic aetiology.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1816167"},"PeriodicalIF":4.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577577","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: Cell therapy in the central nervous system and its crosstalk with the immune system.","authors":"María Norte-Munoz, Raquel Boia, David García-Bernal, Marta Agudo-Barriuso","doi":"10.3389/fncel.2026.1916972","DOIUrl":"https://doi.org/10.3389/fncel.2026.1916972","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1916972"},"PeriodicalIF":4.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577553","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":"Ethanol selectively disrupts neuronal microexon regulation and chromatin marks in PC12 cells.","authors":"Montserrat Olivares-Costa, Pascal Jorratt, Camila Morales, Sebastián F Estay, Adrian R Krainer, María Estela Andrés, Paola A Haeger","doi":"10.3389/fncel.2026.1854045","DOIUrl":"10.3389/fncel.2026.1854045","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to alcohol (ethanol) is the most common toxic insult during human development and is a teratogenic agent associated with abnormalities ranging from behavioral disorders to fetal alcohol syndrome. Ethanol disrupts gene regulatory programs crucial for neuronal identity, including alternative splicing. A distinctive feature of developing neuronal transcriptomes is the high prevalence of microexon inclusion, which consists of short exonic sequences ranging from 3 to 51 nucleotides. However, the impact of ethanol on microexon inclusion remains poorly understood.</p><p><strong>Methods: </strong>In this study, we investigated whether ethanol exposure disrupts neuron-specific alternative splicing programs during neuronal differentiation. To this end, PC12 cells were exposed to 50 mM ethanol throughout five days of NGF-induced differentiation, alongside undifferentiated control cells, to analyze mRNA and protein expression dynamics of key splicing regulators and neurodevelopmental targets.</p><p><strong>Results: </strong>Our data show that in undifferentiated cells, ethanol exposure resulted in a significant reduction in <i>Srrm4</i> expression, while concomitantly increasing <i>Srrm3</i> mRNA levels, consistent with reduced neuron-specific microexon inclusion of the intersectin 1 (<i>Itsn</i>1) mRNA. While undifferentiated PC12 cells primarily express the canonical variants of lysine-specific demethylase 1 (LSD1) and PHD finger protein 21A (PHF21A), differentiation triggers the inclusion of microexons 8a and 14, generating the neuron-specific isoforms neuronal LSD1 and PHF21A, respectively. Under differentiated conditions, ethanol exposure increased neurite length but did not affect the mRNA levels of the neuronal variants of <i>Lsd1</i>, <i>Phf21a,</i> or <i>Itsn1</i>. Notably, ethanol exposure significantly increased the levels of LSD1 protein and its associated histone substrate, H3K4me2, in differentiated PC12 cells.</p><p><strong>Discussion: </strong>Taken together, these findings suggest that ethanol exposure modulates post-transcriptional and chromatin-based mechanisms during neuronal commitment and differentiation. This selective disruption highlights distinct molecular pathways that may contribute to persistent neurodevelopmental alterations relevant to alcohol use disorder, providing new insights into the teratogenic mechanisms of ethanol on the developing nervous system.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1854045"},"PeriodicalIF":4.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561284","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":"Up regulated hippocampal insulin pathway and oxidative stress are related to opposite changes in olfaction and episodic memory in a compensatory metabolic syndrome model in rats.","authors":"Pedro Isauro Clavel-Pérez, Bryan V Phillips-Farfán, Luz Camacho-Castillo, Ana Laura Calderón-Garcidueñas, Karla Carvajal","doi":"10.3389/fncel.2026.1845387","DOIUrl":"10.3389/fncel.2026.1845387","url":null,"abstract":"<p><p>Insulin resistance, a major component of metabolic syndrome (MetS), is involved in phosphorylated tau and beta amyloid buildup, linking MetS to neurodegenerative processes, e.g., Alzheimer's disease. One of the initial signs of neurodegeneration, in diseases such as Parkinson's and Alzheimer's, is olfactory dysfunction. Accordingly, in previous reports we found that high carbohydrate diet based on 30% sucrose in drinking water, increased visceral fat and insulin resistance, leading to an augment of oxidative stress and reduced brain energy metabolism, upregulating amyloidogenic genes (<i>APP</i> and <i>BACE1</i>) in hypothalamus and hippocampus. Thus, herein we comparatively evaluated the effect of sucrose induced MetS on episodic memory, olfaction, protein expression in amyloidogenic and insulin pathways, lipoperoxidation, antioxidant and BACE1 enzymatic activity between the hippocampus and olfactory bulb in male Wistar rats. Also, cellular structure of the olfactory bulb was analyzed. After 24 weeks of 30% sucrose consumption, we found preserved performance in a memory test; decreased hippocampal expression of APP and hyperactivation of the insulin pathway, low levels of lipoperoxidation, and high activity of antioxidant and BACE1 enzymes. Olfactory dysfunction was present in MetS rats, accompanied by morphological alterations in the olfactory bulb along with BACE1 increased activity. Thus, chronic high-sucrose consumption may prime the brain for neurodegenerative processes by modulating insulin signaling, oxidative stress homeostasis and amyloidogenic pathways in a region-dependent manner, with the olfactory system emerging as an early and sensitive target of metabolic dysfunction.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1845387"},"PeriodicalIF":4.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548580","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-brain barrier integrity disruption linked to brain lesions and relapse prediction in Southern Chinese anti-NMDAR encephalitis patients.","authors":"Lingling Tong, Hui Chen, Yanzhen Huang, Wenlin Jiang, Wen Huang","doi":"10.3389/fncel.2026.1872425","DOIUrl":"10.3389/fncel.2026.1872425","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the characteristic brain abnormalities in Southern Chinese patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and to explore their association with blood-brain barrier (BBB) disruption and clinical implications.</p><p><strong>Methods: </strong>This study retrospectively analyzed 80 cases of anti-NMDAR encephalitis. Patients were divided into a group with abnormal brain MRI (<i>n</i> = 35) and a group with normal brain MRI (<i>n</i> = 45). The extent of BBB disruption was assessed using the albumin quotient (Qalb), defined as the cerebrospinal fluid (CSF)-to-serum albumin ratio. Disease severity was evaluated using the modified Rankin Scale (mRS). Patients were further categorized into a relapse group and a non-relapse group based on post-discharge relapse status. Key predictive factors were identified through multivariate regression analysis.</p><p><strong>Results: </strong>Brain MRI abnormalities were observed in 43.75% (35/80) of the anti-NMDAR encephalitis patients. Among these, typical MRI findings of anti-NMDAR encephalitis abnormalities were present in 26 patients (32.5% of the total cohort). Brain MRI abnormalities were significantly associated with abnormal BBB permeability (42.9% vs. 13.3%, <i>p</i> = 0.003). Multivariate logistic regression analysis identified two independent predictive factors for brain MRI abnormalities: BBB dysfunction (OR = 4.088, 95% CI: 1.031-16.213, <i>p</i> = 0.045) and time from symptom onset to first-line immunotherapy (OR = 1.041, 95% CI: 1.001-1.083, <i>p</i> = 0.045). Furthermore, receiver operating characteristic (ROC) curve analysis demonstrated that the combined model of BBB dysfunction and time from symptom onset to first-line immunotherapy exhibited favorable predictive performance, with an area under the curve (AUC) of 0.745 (95% CI: 0.634-0.857). BBB dysfunction was closely associated with multi-regional cerebral involvement (<i>p</i> = 0.002). Further Spearman correlation analysis showed that impaired BBB integrity correlated with greater MRI lesion severity and broader lesional distribution (<i>p</i> = 0.003). In binary logistic regression analysis adjusting for mRS score, positive oligoclonal bands (OCBs) were identified as a potential predictor of relapse, with an OR of 7.991 (95% CI: 1.242-51.411, <i>p</i> = 0.029). The AUC was 0.730 (95% CI: 0.542-0.918), indicating moderate predictive performance.</p><p><strong>Conclusion: </strong>Abnormal BBB permeability is an independent risk factor for structural abnormalities on brain MRI and is positively correlated with the extent of MRI abnormalities. CSF OCB positivity is a risk factor for disease relapse. These findings may inform brain injury assessment, relapse risk stratification, and individualized treatment in patients with anti-NMDAR encephalitis.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1872425"},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520044","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":"Siglec-1 upregulation and macrophage activation in age-related hearing loss: insights from integrated transcriptomic studies in mice and humans.","authors":"Di Ji, Qian Li, Baiyang Ren, Hongli Lan, Wenqi Zuo, Tao Chen, Xin Gong, Sen Yang, Anchun Deng, Shixun Zhong","doi":"10.3389/fncel.2026.1879068","DOIUrl":"10.3389/fncel.2026.1879068","url":null,"abstract":"<p><p>Macrophage activation is closely associated with age-related hearing loss (ARHL), and Siglec-1 may be involved in modulating macrophage activation. This study aimed to investigate the immunological mechanisms underlying spiral ganglion neuron (SGN) degeneration in ARHL, with a focus on the roles of the immune regulatory gene Siglec-1 and immune regulatory cells, macrophages. Combined transcriptomic sequencing of SGNs from ARHL mice and peripheral blood samples from ARHL patients identified significant upregulation of Siglec-1 in aged groups. Auditory brainstem response (ABR) testing and histological analysis confirmed that hearing thresholds increased and SGN density decreased significantly with age, exhibiting a strong negative correlation. Subsequently, both immunofluorescence and Western blot analyses revealed a notable upregulation of Siglec-1 expression within the spiral ganglion of aged mice. Further RT-PCR analysis revealed that the expression levels of both pro-inflammatory cytokines (including IL-6, TNF-<i>α</i>, and IFN-<i>γ</i>) and the anti-inflammatory cytokine IL-10 were significantly elevated in the aging spiral ganglion tissue. Meanwhile, notable macrophage activation was observed within the spiral ganglion, particularly involving M1 pro-inflammatory macrophages. These findings suggest that Siglec-1 may play a role in the inflammatory response. Finally, we also confirmed a positive correlation between Siglec-1 mRNA expression in human blood samples with age and severity of hearing loss. These findings suggest that Siglec-1 may promote SGN degeneration in ARHL by modulating macrophage-mediated neuroinflammation and represents a potential blood immune biomarker and therapeutic target.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1879068"},"PeriodicalIF":4.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469734","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":"Pharmacological activation of cGMP signaling promotes astrocyte remodeling and enrichment of perivascular GLUT1 in the murine retina.","authors":"Kristin L Clark, Shane Mecca, Elio Almaoui, Olivia L Bossardet, Joseph M Holden, David J Calkins, Lauren K Wareham","doi":"10.3389/fncel.2026.1870679","DOIUrl":"10.3389/fncel.2026.1870679","url":null,"abstract":"<p><p>Astrocytes regulate metabolic exchange between the vasculature and neurons in the central nervous system (CNS). In the retina of the eye, also a component of the CNS, astrocyte endfeet couple to vascular elements to mediate glucose uptake via the glucose transporter GLUT1 and shuttle metabolic resources to the axons of retinal ganglion cells (RGCs), which provide visual input to the brain. In addition to its own transcriptional regulation, GLUT1 is also modulated by signaling pathways that influence its subcellular localization at the astrocyte-vascular interface. For example, cyclic guanosine monophosphate (cGMP) signaling, a key regulator of vascular tone, is associated with changes in retinal astrocyte morphology and is implicated in age-related loss of RGCs, suggesting a potential role in astrocyte function within the neurovascular unit. Here, we tested this possibility directly by investigating the effects of 8-Br-cGMP on astrocyte morphology, vascular interactions, and GLUT1 localization in the retina. Using a transgenic mouse that allows resolution of individual astrocytes in great detail across the retina (the G-MORF mouse), we show that acute elevation of 8-Br-cGMP increases astrocyte coverage area without altering overall vascular structure. 8-Br-cGMP treatment was also associated with enhanced astrocyte-vascular association, reflected by increased endfoot coverage of blood vessels and altered scaling of astrocyte contact with vessel size. Treatment to increase cGMP signaling promoted redistribution of GLUT1 to astrocyte perivascular endfeet without changing overall levels of GLUT1. Together, these findings indicate that increased cGMP signaling induces coordinated structural and molecular remodeling of astrocytes at the vascular interface. These results provide important insight into how cyclic nucleotide signaling pathways may regulate astrocyte organization in the retina and suggests a potential role for cGMP in modulating astrocyte-vascular interactions within the neurovascular unit.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1870679"},"PeriodicalIF":4.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455066","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":"Mice lacking two alleles of the schizophrenia risk gene <i>Tcf4</i> and <i>Olig2</i> display deficits in anxiety-related behavior, sensorimotor gating, and cognition.","authors":"Man-Hsin Chang, Ruofan Li, Marius Stephan, Andrea Schmitt, Peter Falkai, Moritz J Rossner","doi":"10.3389/fncel.2026.1837159","DOIUrl":"10.3389/fncel.2026.1837159","url":null,"abstract":"<p><strong>Introduction: </strong>Oligodendrocytes (OLs) and myelination contribute to higher-order cognitive functions, and are impaired in several mental disorders, including schizophrenia (SZ). The SZ risk gene <i>transcription factor 4</i> (<i>TCF4</i>) and <i>OLIG2</i> are two critical regulators of differentiation and maturation of oligodendrocyte precursor cells (OPCs) and OLs. <i>Tcf4</i>-<i>Olig2</i> double heterozygous deletion (<i>Tcf4</i>-<i>Olig2</i> dHet) mice have been shown to exhibit impairments in OL differentiation and myelination.</p><p><strong>Methods: </strong>Therefore, we performed a comprehensive behavioral profiling using a Research Domain Criterion (RDoC)-based pipeline in this model.</p><p><strong>Results: </strong><i>Tcf4</i>-<i>Olig2</i> dHet mice showed impaired place learning in the positive valence system, reduced anxiety-like behaviors in the negative valence system, impaired remote fear memory in the cognitive domain, and abnormal sensorimotor gating.</p><p><strong>Discussion: </strong>Thus, subtle OLs and myelination impairments in <i>Tcf4</i>-<i>Olig2</i> dHet mice led to several psychiatric disorder-related behavioral deficits. We conclude that <i>Tcf4</i>-<i>Olig2</i> dHet mice represent a preclinical mouse model to study myelination-related mechanisms relevant for mental disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1837159"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445480","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":"TGFβ signalling maintains Sox4+ astrocyte progenitors and restricts the early differentiation of BLBP+ astrocytes in the mouse dentate gyrus.","authors":"Kyoji Ohyama, Shoichiro Omura, Natsumi Takayama, Tokiharu Takahashi","doi":"10.3389/fncel.2026.1882016","DOIUrl":"10.3389/fncel.2026.1882016","url":null,"abstract":"<p><p>Astrocytes in the mouse hippocampal dentate gyrus (DG) derive, at least in part, from BLBP+ cells, but the mechanism that controls the onset of their differentiation remains poorly understood. To address this, we first characterised the developmental dynamics of BLBP+ cells using Ki67 and the cyclin-dependent kinase inhibitor p57. Ki67+/BLBP+ proliferative progenitors peaked at P1 and declined by P3-P6, when p57+/BLBP+ early-differentiating astrocytes instead accumulated. This temporal switch prompted us to examine what maintains the proliferative pool and restricts premature differentiation. We identified Sox4, a downstream transcription factor of TGFβ signalling, as a selective marker of the undifferentiated astrocytic lineage in the developing DG. At E15-E17, Sox4 was co-expressed with BLBP and pVimentin in basal radial glia (bRG), and at P1-P6 with BLBP, Sox3 and Ki67 in proliferative glial progenitors including the Olig2+/BLBP+ astrocyte progenitors (ASPs) we recently identified. Our data further suggest that Sox4 marks ASPs but not either NeuroD+ neuronal progenitors or p57+/BLBP+ early-differentiating astrocytes. From P14 onwards, Sox4 expression persisted in a subpopulation of BLBP+ radial glia-like cells (RGLs) at the SGZ and in BLBP+ cells in the molecular layer. Together, these data suggest that Sox4 selectively marks BLBP+ glial progenitors (bRG, RGLs and ASPs) but not their differentiated progeny. Consistent with an autocrine TGFβ1-Sox4 pathway described in glioma-initiating cells, TGFβ1 was co-expressed with BLBP in bRG, RGLs and ASPs. Blockade of TGFβ signalling with SB431542 in DG explants depleted Sox4+ progenitors and, in turn, promoted the accumulation of p57+/BLBP+ astrocytes. Our data thus suggest that TGFβ signalling maintains Sox4+ progenitors and thereby restricts the early differentiation of BLBP+ astrocytes in the mouse DG.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1882016"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445453","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":"Astrocytes in systemic regulation of blood glucose and the development of type 2 diabetes.","authors":"Zhen Wen, Peng Bai, Li Du, Qianru Zhao, Mengliu Yang, Jialin Shan, Xiang Hu, Jie Min, Kangli Qiu, Yunfei Liao, Tianshu Zeng, Nan Zhang","doi":"10.3389/fncel.2026.1850636","DOIUrl":"10.3389/fncel.2026.1850636","url":null,"abstract":"<p><p>The central nervous system (CNS) relies primarily on glucose for energy, and therefore maintaining peripheral glucose homeostasis is essential to ensure adequate CNS energy supply and normal physiological functions. Historically, hypothalamic neurons-particularly defined glucose-sensing neuronal populations-were considered the main sensors and regulators of systemic glucose, while astrocytes primarily serving a nutritional and supportive role for neurons. However, recent studies have progressively revealed that astrocytes also play a significant role in systemic glucose regulation, particularly within the hypothalamus. In this review, we discuss the molecular mechanisms by which hypothalamic astrocytes sense glucose and modulate glucose homeostasis, and we examine how astrocyte-neuron interactions cooperate to maintain systemic glucose balance. We also summarize evidence that astrocytes in other regions, such as the hindbrain, participate in glucose regulation. Finally, we consider how altered astrocyte function may contribute to the development and progression of type 2 diabetes through changes in metabolism and inflammatory or signaling pathways. Research in this field not only expands our understanding of glial cell functions in metabolic regulation but also provides novel potential intervention targets for diseases associated with energy homeostasis imbalance, such as diabetes.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1850636"},"PeriodicalIF":4.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445466","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}