Neurobiology of Disease最新文献

{"title":"RhoA deletion in macrophages/microglia aggravates blood-brain barrier disruption after ischemic stroke reperfusion injury by promoting endothelial cell apoptosis and pyroptosis","authors":"Jiale Cai ,&nbsp;Xiongbo Luo ,&nbsp;Wenli Cui ,&nbsp;Xinya Zheng ,&nbsp;Shuyi Xu ,&nbsp;Xinrui Ma ,&nbsp;Ye He ,&nbsp;Xianghai Wang ,&nbsp;Jiasong Guo","doi":"10.1016/j.nbd.2026.107279","DOIUrl":"10.1016/j.nbd.2026.107279","url":null,"abstract":"<div><div>Disruption of the blood-brain barrier (BBB) is an important cause of secondary injury following cerebral ischemia-reperfusion (I/R). Database analyses revealed RhoA upregulation in macrophages/microglia within I/R brain tissue; however, the role of macrophage/microglial RhoA in BBB disruption and I/R injury remains poorly understood. In this study, we verified that macrophage/microglial RhoA was significantly upregulated in I/R mice. Employing conditional knockout (cKO) mice, present study demonstrated that the macrophage/microglial RhoA deficiency exacerbates I/R injury, manifesting as enlarged infarct volumes, aggravated cerebral oedema and BBB leakage. Mechanistically, RhoA deficiency alters the secretory profile of macrophages/microglia, enhancing pro-inflammatory factors production in macrophages/microglia, which subsequently induces pyroptosis and apoptosis while downregulates tight junction proteins in endothelial cells via the NLRP3 pathway. Collectively, our findings revealed a novel macrophage/microglial-endothelial crosstalk mechanism whereby I/R-induced RhoA upregulation in macrophages/microglia serves to attenuate their pro-inflammatory polarization, thereby preserving BBB function through suppression of NLRP3-mediated pyroptosis and apoptosis in the endothelial cells. These findings may reshape the conventional view of RhoA inhibition therapy and pave the way for more precise, cell-targeted interventions in I/R brain injury.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107279"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived neural organoids reveal developmental impairments associated with a novel GJB1 mutation in X-linked Charcot-Marie-Tooth disease","authors":"Jianying Guo ,&nbsp;Qianhui Lee ,&nbsp;Hui Qiu ,&nbsp;Yuan Wei ,&nbsp;Xiaohui Zhu ,&nbsp;Liying Yan ,&nbsp;Jie Na","doi":"10.1016/j.nbd.2026.107299","DOIUrl":"10.1016/j.nbd.2026.107299","url":null,"abstract":"<div><div>Charcot-Marie-Tooth disease (CMT) is one of the most prevalent inherited peripheral neuropathies. CMT type X1 (CMTX1), caused by mutations in the <em>GJB1</em> gene, represents the most common X-linked subtype with central nervous system (CNS) involvement. Here, we report the identification and functional characterization of a novel <em>GJB1</em> variant (c.554C &gt; T, p.Thr185Ile) in a CMTX1-affected family and its pathogenic impact using patient-derived induced pluripotent stem cells (iPSCs) and three-dimensional (3D) neural organoid models. The <em>GJB1</em> gene encodes connexin 32 (Cx32), a gap junction protein. Immunofluorescent analysis revealed aberrant intracellular reduction and aggregation of the mutant Cx32 protein, suggesting impaired gap junction function. iPSC-derived neural organoids carrying the <em>GJB1</em> mutation exhibited significant delay in neural differentiation and disrupted neural rosette organization. These findings underscore the critical role of Cx32 in neural development and provide a physiologically relevant platform for underlying CMTX1 pathological mechanisms on central nervous system. The established <em>GJB1</em>-variant organoid model holds promise for investigating genotype-phenotype correlations and facilitating the development of targeted therapeutic strategies for CMTX1.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107299"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The apolipoprotein gene: a modulating role on brain volume and cognitive function in carriers of the fragile X premutation","authors":"Poonnada Jiraanont ,&nbsp;Jun Yi Wang ,&nbsp;Blythe Durbin-Johnson ,&nbsp;Ye Hyun Hwang ,&nbsp;David Hessl ,&nbsp;Susan M. Rivera ,&nbsp;Randi J. Hagerman ,&nbsp;Flora Tassone","doi":"10.1016/j.nbd.2026.107292","DOIUrl":"10.1016/j.nbd.2026.107292","url":null,"abstract":"<div><div>Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by the <em>FMR1</em> premutation allele, is associated with brain degeneration, yet the mechanisms behind this neurodegeneration still need to be elucidated. <em>Apoε</em> polymorphism has been widely implicated in brain aging in cognitively healthy individuals and brain deterioration in Alzheimer's disease. This study aimed to examine the interaction of <em>Apoε</em> genotypes, FXTAS clinical symptoms, <em>FMR1</em> molecular measures, and age, towards brain pathophysiology and cognitive functions.</div><div>This longitudinal study includes MRI data collected from 205 male premutation carriers with and without FXTAS clinical symptoms and compared to 86 healthy male controls aged 40–85 years. The investigation includes FXTAS-related brain volumes, IQ, self-control behaviors, <em>FMR1</em> molecular measures, and <em>Apoε</em> genotypes.</div><div>In carriers with FXTAS, the presence of the <em>Apoε2</em> allele showed a possible association with more favorable neuroimaging markers, such as reduced white matter hyperintensities, and lower incidence of the middle cerebellar peduncle sign, patterns that were not observed in carriers without FXTAS.</div><div>Specifically, the presence of <em>Apoε2</em> allele exhibited a potential protective effect on brain degeneration, and cognitive functions among FXTAS patients; on the contrary, the <em>Apoε4</em> allele was associated with a worsening of brain volume and brain degeneration in carriers with no FXTAS symptoms. The identification of <em>Apoε</em> genotypes in <em>FMR1</em> premutation carriers before any clinical symptoms of FXTAS are observed may improve symptomatic management leading to better outcomes for these individuals.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107292"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological manipulation of nested oscillations in human iPSC-derived 2D neuronal networks","authors":"Deborah Pré ,&nbsp;Christian Cazares ,&nbsp;Alexander T. Wooten ,&nbsp;Haowen Zhou ,&nbsp;Isabel Onofre ,&nbsp;Ashley Neil ,&nbsp;Todd Logan ,&nbsp;Ruilong Hu ,&nbsp;Jan H. Lui ,&nbsp;Bradley Voytek ,&nbsp;Anne G. Bang","doi":"10.1016/j.nbd.2026.107281","DOIUrl":"10.1016/j.nbd.2026.107281","url":null,"abstract":"<div><div>Dynamically coupled neural networks are fundamental to human cognition and behavior and are disrupted in neurodevelopmental disorders. The formation and dissolution of functional networks is thought to be driven by synchronized oscillatory bursts across large populations of neurons. The mechanisms driving the emergence of these rhythms, known as oscillogenesis, are not well understood, particularly in the human brain. Using multi-electrode arrays, we investigated oscillogenesis in human induced pluripotent stem cell 2D neural cultures at different developmental stages and under pharmacological challenges. We found that cultures exhibited nested oscillations that were reduced by GABAA receptor blockade and emerged earlier when the proportion of GABAergic neurons was increased. Pharmacological manipulations of voltage-gated potassium channels and cholinergic receptors modulated the pattern of nested oscillations. These results reveal the capacity of these 2D cultures to model oscillogenesis, and underscore the need for their continued refinement, paving the way for linking systems-level neural networks to human cognition and disease.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107281"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between diseases of the mouth and mental disorders: A scoping review of longitudinal studies","authors":"Sudan Prasad Neupane ,&nbsp;Ifeoma N. Onyeka ,&nbsp;Vibeke H. Bull ,&nbsp;Federico M. Daray","doi":"10.1016/j.nbd.2026.107285","DOIUrl":"10.1016/j.nbd.2026.107285","url":null,"abstract":"<div><h3>Background</h3><div>Mental disorders and oral health conditions frequently co-occur. We mapped and critically reviewed the literature on longitudinal associations between oral health conditions and mental disorders.</div></div><div><h3>Method</h3><div>MEDLINE, Embase and PsycInfo were searched for longitudinal studies published during the last 25 years. Two reviewers independently screened, reviewed full-text and extracted data before synthesizing the evidence. Associations between oral and mental disorders were illustrated as Sankey diagrams. The review protocol was pre-registered (<span><span>https://osf.io/vrpu9</span><svg><path></path></svg></span>).</div></div><div><h3>Findings</h3><div>From 165 included studies, we identified 118 studies investigating 35 independent associations between 16 oral exposures and 12 mental disorder outcomes. Another 42 studies investigated 32 associations between 17 mental disorder exposures and 14 oral outcomes. Five studies reported bidirectional associations. Most reports linked tooth loss to Alzheimer's disease/other dementias (18 studies) and cognitive impairment (15 studies), with periodontitis linked to Alzheimer's disease/other dementias (16 studies). Conversely, depression (10 studies), dementia (6 studies) and sleep disorder (5 studies) were attributed to temporomandibular disorders (TMD; 10 studies), periodontitis (8 studies) and caries (7 studies) outcomes. Depressive and anxiety disorders were linked bidirectionally with TMD and eating disorders.</div></div><div><h3>Interpretation</h3><div>Prevention and early management of oral and mental disorders may mitigate their reciprocal risk, thereby lowering the overall disease burden.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107285"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal cord reactive-antibodies identified by serological antigen selection show prognostic value in traumatic spinal cord injury patients","authors":"Astrid Pues ,&nbsp;Patrick Vandormael ,&nbsp;Tim Vangansewinkel ,&nbsp;Naomi Veeningen ,&nbsp;Sam Vanherle ,&nbsp;Charlotte C.M. van Laake-Geelen ,&nbsp;Erwin M.J. Cornips ,&nbsp;Dieter Peuskens ,&nbsp;Eveleen Buelens ,&nbsp;Jens Deckers ,&nbsp;Bart Depreitere ,&nbsp;Sven Bamps ,&nbsp;Marc J. Ruitenberg ,&nbsp;Angel Arevalo-Martin ,&nbsp;Daniel Garcia-Ovejero ,&nbsp;Lukas Grassner ,&nbsp;Orpheus Mach ,&nbsp;Iris Leister ,&nbsp;Judith Fraussen ,&nbsp;Veerle Somers","doi":"10.1016/j.nbd.2026.107306","DOIUrl":"10.1016/j.nbd.2026.107306","url":null,"abstract":"<div><div>Outcome prediction after traumatic spinal cord injury (SCI) remains challenging due to patient heterogeneity, highlighting the need for better prognostic tools. Neural tissue damage and blood–spinal cord barrier disruption expose the immune system to spinal cord proteins, eliciting autoantibody responses that may be beneficial or detrimental. This study aimed to identify the (auto)antibody profile of SCI patients, and examine the prognostic antibody biomarker potential.</div><div>A healthy and a SCI cDNA phage display library were screened for novel antibodies using SCI samples (<em>n</em> = 12/11). Antibody reactivity was validated using phage ELISA in 291 samples from 190 SCI patients collected at baseline (0–4 days post-injury [dpi]) and follow-up (15–30 dpi; 31–56 dpi). Correlations between antibody reactivity and clinical characteristics including SCI level, and American Spinal Injury Association impairment scale (AIS), were analysed. Immunofluorescent stainings were used to validate expression of two antigenic targets.</div><div>We identified antibodies against 6 novel autoantigens (University Hasselt [UH.] SCI.104/105/106/108/109/110). A panel of three antigens (UH.SCI.104/109/110) demonstrated increased antibody reactivity in 31.3% of SCI patients with AIS improvement versus 4.8% with no improvement, resulting in a positive likelihood ratio of 6.56. Patients with injuries above thoracic level 4 had significantly lower antibody reactivity against UH.SCI.105/110 compared to patients with lower lesions. Anti-UH.SCI.108/110 antibodies bound to astrocytes, in mouse spinal cord tissue and primary cell cultures, confirming disease-relevant reactivity.</div><div>Antibodies targeting the novel antigens demonstrated prognostic biomarker potential, supporting their future use in outcome prediction and patient stratification for SCI management and clinical trial design.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107306"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New perspective on neurodegenerative diseases: Focusing on the interaction between autophagy and oxidative stress and targeted strategies","authors":"Jiaqin Jin ,&nbsp;Qiuyu Cen ,&nbsp;Huage Wang ,&nbsp;Yin Xin ,&nbsp;Jing Feng ,&nbsp;Yanru Cui ,&nbsp;JiaYu Li ,&nbsp;Zilong You ,&nbsp;Fangyuan Jing ,&nbsp;Yang Yu ,&nbsp;Yingbo Qiu ,&nbsp;Rizhao Pang ,&nbsp;Junyu Wang ,&nbsp;Anren Zhang","doi":"10.1016/j.nbd.2026.107283","DOIUrl":"10.1016/j.nbd.2026.107283","url":null,"abstract":"<div><div>Autophagy is a highly conserved lysosome-dependent degradation process that plays a crucial role in maintaining neuronal homeostasis and adaptation during stress by eliminating misfolded proteins, damaged organelles, and pathogens. Oxidative stress, triggered by an imbalance between reactive oxygen speciesreactive oxygen species:ROS (ROS) production and antioxidant defenses, contributes to disease pathogenesis through mechanisms such as lipid peroxidation, protein carbonylation, and mitochondrial DNA damage. Recent studies reveal that autophagy and oxidative stress interact via a dynamic bidirectional regulatory network to modulate neurodegenerative pathology: ROS activate autophagy by regulating signaling pathways and modifying autophagy-associated proteins, while moderate autophagic activity selectively clears ROS-generating components and activates antioxidant pathways. Dysregulation of autophagy or excessive ROS accumulation can disrupt this equilibrium, leading to cell death and disorders such as neurodegenerative diseases, cancer, and aging-related pathologies. They reciprocally serve as “pressure signals” and “clearance targets”, synergistically maintaining cellular homeostasis. This review synthesizes insights from current studies to systematically analyze the complex cross-talk between autophagy and oxidative stress in neurodegeneration and evaluates emerging therapeutic strategies targeting this interplay, including autophagy modulators, antioxidants, phytochemicals, and nanomaterials. These advancements offer novel perspectives for developing neuroprotective therapies through therapeutic modulation of the autophagy-oxidative stress axis. Finally, we summarize key challenges in the field and propose potential directions for future research.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107283"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of auxiliary GABAB receptor subunit KCTD16 in pain modulation","authors":"Daniel Vasconcelos ,&nbsp;Mario Heles ,&nbsp;Pavel Adamek ,&nbsp;Anirban Bhattacharyya ,&nbsp;Adolf Melichar ,&nbsp;Rostislav Turecek ,&nbsp;Jiri Palecek","doi":"10.1016/j.nbd.2026.107286","DOIUrl":"10.1016/j.nbd.2026.107286","url":null,"abstract":"<div><div>Chronic pain affects nearly 10% of the global population and remains a major clinical challenge due to the limited efficacy and adverse effects of current therapies. In this study, we identify the potassium channel tetramerization domain protein KCTD16 as a key modulator of GABA_B receptor mediated inhibition of nociceptive transmission. Immunohistochemical analysis revealed prominent KCTD16 expression in dorsal horn and dorsal root ganglion (DRG) neurons, consistent with a role in spinal nociceptive processing. KCTD16 knockout (KO) mice exhibited increased mechanical thresholds relative to wild-type (WT) littermates, while thermal sensitivity remained unchanged; this phenotype persisted following carrageenan-induced inflammation. The GABA_B receptor agonist Baclofe<strong>n</strong> produced strong analgesic effects in WT mice under both basal and inflammatory conditions, whereas its anti-allodynic efficacy was significantly reduced in KO animals. Whole-cell patch-clamp recordings from dorsal horn neurons showed comparable baseline miniature excitatory and lower inhibitory postsynaptic currents (mEPSCs and mIPSCs) for KCTD16^−/−. However, following inflammation, Baclofen-induced suppression of excitatory transmission was potentiated in WT but markedly attenuated in KO neurons. Light-evoked synaptic inhibitory currents and calcium imaging of cultured DRG neurons further demonstrated enhanced Baclofen sensitivity in WT cells. These findings indicate that KCTD16 plays a critical role in presynaptic modulation of inhibitory control in the spinal dorsal horn, affecting the balance between the excitation and inhibition in nociceptive circuits. Collectively, these results demonstrate that KCTD16 modulates GABA_B receptor-dependent inhibitory control of nociceptive signaling and highlight the GABA_B receptor-KCTD16 complex as a promising new molecular target for effective pain treatments.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107286"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and machine learning in neurodegenerative disease management: A 21st century paradigm","authors":"Shaik Basha ,&nbsp;Pranavi KS ,&nbsp;Ahana Chattopadhyay ,&nbsp;Aparna Ramakrishna Pai ,&nbsp;Krishna Kishore Mahato","doi":"10.1016/j.nbd.2026.107307","DOIUrl":"10.1016/j.nbd.2026.107307","url":null,"abstract":"<div><div>Neurodegenerative diseases represent a major and growing clinical challenge due to their progressive nature, biological heterogeneity, and limited therapeutic options. Recent advances in artificial intelligence (AI) have introduced new analytical strategies for extracting clinically relevant information from complex biomedical data, offering complementary tools to established diagnostic and research approaches. This review provides a critical and method-comparative synthesis of AI applications in neurodegenerative diseases, with emphasis on studies published between 2022 and 2025. Rather than cataloging algorithms, the review evaluates how specific AI methodologies are selected, implemented, and validated across diverse data modalities, including molecular profiles, neuroimaging, biosensors, speech, gait, and electronic health records. Across Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders, the reviewed evidence indicates that AI-based models can support early risk stratification, disease characterization, and monitoring when applied within clearly defined analytic and clinical contexts. Importantly, performance gains are shown to depend strongly on data quality, feature representation, validation design, and alignment between model architecture and biological signal, rather than on algorithmic complexity alone. Emerging paradigms, including multimodal integration and next-generation AI frameworks, are discussed in relation to their methodological contributions rather than clinical readiness. By systematically comparing analytical strategies and highlighting sources of variability across studies, this review underscores the importance of methodological transparency, uncertainty-aware evaluation, and biological interpretability. Collectively, the work positions AI as an enabling and adjunctive analytical framework that can enhance neurodegenerative disease research and clinical decision support when deployed with rigor and caution, providing a balanced perspective on current capabilities and future directions.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107307"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal glial alterations are associated with Lamin B1 dysregulation and abnormal nuclear morphology in a rat model of fragile X syndrome","authors":"Alessandro Rava ,&nbsp;Alessandro Feo ,&nbsp;Giulia Bagnato ,&nbsp;Valentina D’Oria ,&nbsp;Marco Pezzullo ,&nbsp;Stefania Petrini ,&nbsp;Valeria Buzzelli ,&nbsp;Fabrizio Ascone ,&nbsp;Melania Di Trapano ,&nbsp;Barbara Peruzzi ,&nbsp;Viviana Trezza","doi":"10.1016/j.nbd.2026.107304","DOIUrl":"10.1016/j.nbd.2026.107304","url":null,"abstract":"<div><div>Fragile X syndrome (FXS) is the most common inherited intellectual disability and the leading monogenic cause of autism spectrum disorders (ASD). Although the pathological mechanisms underlying this neurodevelopmental disorder are challenging, recent studies have increasingly highlighted the involvement of glial cells in the pathogenesis of both ASD and FXS. Microglia and astrocytes are critical for brain development and homeostasis; thus, understanding glial dysfunction in both the developing and adult brain in these disorders may reveal novel therapeutic targets beyond the neuro-centric perspective. In this study, we demonstrated that the loss of function of Fmrp leads to phenotypic changes in both microglia and astrocytes within the hippocampus of the recently validated <em>Fmr1-</em>^<em>∆</em><em>exon 8</em> rat model of FXS without a significant induction of pro-inflammatory cytokines. For the first time, we also provide evidence that these non-inflammatory changes in glia are associated with dysmorphic nuclei and a reduced expression of Lamin B1, a key component of the nuclear envelope and an important modulator of brain development and aging, in the hippocampus of young adult <em>Fmr1-</em>^<em>∆</em><em>exon 8</em> rats.</div><div>Collectively, our findings strengthen existing evidence of the glial contribution to FXS and identify Lamin B1 loss and nuclear abnormalities as potential early markers of hippocampal pathology, providing a novel potential molecular target which should be furtherly considered.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"220 ","pages":"Article 107304"},"PeriodicalIF":5.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}