Neurobiology of Disease最新文献

{"title":"Glymphatic dysfunction is related to motor disability fully mediated by gray matter degeneration in early-stage Parkinson's disease","authors":"Zihao Zhu ,&nbsp;Xiaojie Duanmu ,&nbsp;Cheng Zhou ,&nbsp;Jiaqi Wen ,&nbsp;Jianmei Qin ,&nbsp;Qianshi Zheng ,&nbsp;Weijin Yuan ,&nbsp;Tao Guo ,&nbsp;Haoting Wu ,&nbsp;Chenqing Wu ,&nbsp;Jingwen Chen ,&nbsp;Jingjing Wu ,&nbsp;Yingni Jin ,&nbsp;Nan Lu ,&nbsp;Lu Wang ,&nbsp;Bingting Zhu ,&nbsp;Yuelin Fang ,&nbsp;Lifang Wang ,&nbsp;Ziyi Zhu ,&nbsp;Yaping Yan ,&nbsp;Xiaojun Xu","doi":"10.1016/j.nbd.2025.107001","DOIUrl":"10.1016/j.nbd.2025.107001","url":null,"abstract":"<div><h3>Background</h3><div>Glymphatic dysfunction plays a critical role in Parkinson's disease (PD), but its impact on neurodegeneration and clinical symptoms in the early-stage remains unclear. This study investigates the relationship between glymphatic dysfunction, gray matter (GM) degeneration, and clinical deterioration in early-stage PD.</div></div><div><h3>Methods</h3><div>A total of 249 early-stage PD patients and 114 healthy controls (HC) underwent T1-weighted and DTI scans, along with clinical assessments. Among them, 83 patients and 32 HC were longitudinally re-visited. The diffusion tensor imaging along the perivascular space (DTI-ALPS) index was used to estimate glymphatic function. Linear mixed model was performed to identify longitudinal GM degeneration and clinical deterioration; partial correlation analysis was applied to explore GM degeneration associated with glymphatic dysfunction; while mediation analysis was conducted to investigate the mediation role of GM degeneration in the relationship between glymphatic dysfunction and clinical deterioration.</div></div><div><h3>Results</h3><div>Significantly lower DTI-ALPS index was observed in PD patients, which correlated with reduced cortical thickness in the bilateral posterior cingulate and left lingual gyrus at baseline, and faster atrophy in the left rostral anterior cingulate during follow-up. The relationship between DTI-ALPS index and baseline motor disability was fully mediated by the degeneration of the left posterior cingulate.</div></div><div><h3>Conclusion</h3><div>Glymphatic dysfunction in early-stage PD correlates with GM degeneration and motor decline. Left posterior cingulate degeneration fully mediates the impact of glymphatic dysfunction on motor disability. These findings deepen the understanding of the clinical relevance of glymphatic dysfunction and provide further insights into the regulatory mechanisms underlying PD-related neurodegenerative circuits.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107001"},"PeriodicalIF":5.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280694","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":"Frequency-coded spatiotemporal control of telencephalic ictal oscillations and inter-cortical coherence by thalamus","authors":"Ping Chou ,&nbsp;Yi-Chen Lai ,&nbsp;Yen-Hsin Zheng ,&nbsp;Ya-Chin Yang ,&nbsp;Chung-Chin Kuo","doi":"10.1016/j.nbd.2025.106993","DOIUrl":"10.1016/j.nbd.2025.106993","url":null,"abstract":"<div><div>Many epileptic seizures (hereafter abbreviated as seizures) are characterized by overly synchronized oscillating activities in the thalamocortical system. Despite dense reciprocal innervation between cortex and thalamus, the exact role of thalamus in ictogenesis (e.g. as a passive associate, lenient modulator, or indispensable controller) has been unsettled. We found that either electrical or chemical ictogenic stimulation of basolateral amygdala (BLA) induces augmentation of δ-frequency local field potential (LFP) oscillations in situ. In contrast, the thalamic mediodorsal nucleus (MD), which is reciprocally connected with BLA, responds with mixed θ-α and δ oscillations at first. MD may then be entrained more and more into the latter, leading to augmented δ oscillations as well as δ coherence in the thalamocortical system and maximal behavioral seizures. Inhibition of MD with topical tetrodotoxin dissipates the coherent δ augmentation and decreases multi-unit spikes in BLA and other telencephalic areas, suggesting critical involvement of MD in the inter-cortical communication and focal ictogenesis. Systemic application of proconvulsant pentylenentetrazol could induce interchanging periods of δ and θ-α augmentation in MD, at which periods concomitant electrical stimulation of BLA would be much more and less likely to induce seizures, respectively. The mechanism underlying thalamic δ entrainment in telencephalic ictogenesis and “θ-α antagonism” may involve local GABA-glutamate interactions and the requirement of cortical glutamatergic input for the generation of thalamic burst discharges (“relay bursts\"). Thalamus thus assumes a critical control of the temporal pace and spatial scale of telencephalic oscillations, with a specific but well adaptable order of frequency and amplitude modulation.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106993"},"PeriodicalIF":5.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285773","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":"Dynamic alterations of SEEG characteristics during peri-ictal period and localization of seizure onset zone","authors":"Lidao Xu ,&nbsp;Yongxin Yang ,&nbsp;Qinghua Tan ,&nbsp;Hongping Tan ,&nbsp;Yifan Wang ,&nbsp;Zeliang Hou ,&nbsp;Jingxian Shen ,&nbsp;Rihui Li ,&nbsp;Yuxi Luo ,&nbsp;Lizhang Zeng ,&nbsp;Qiang Guo ,&nbsp;Xuchu Weng ,&nbsp;Jiuxing Liang","doi":"10.1016/j.nbd.2025.106998","DOIUrl":"10.1016/j.nbd.2025.106998","url":null,"abstract":"<div><h3>Background</h3><div>The evolution in peri-ictal period (from pre-ictal to ictal phase) of seizures contains abundant epileptogenic information, which aids in exploring the mechanism of seizures and localizing the epileptogenic zone (EZ). This study aims to investigate the regulatory mechanisms of seizure and localize EZ by analyzing the dynamic alterations of diverse characteristics during peri-ictal period based on SEEG.</div></div><div><h3>Methods</h3><div>A total of 61 patients with refractory focal epilepsy were included, and each patient underwent SEEG electrodes implantation. The data in the peri-ictal period were selected, and the dynamic alterations of phase-amplitude coupling (MI), connectivity strength (wPLI, DTF), and sample entropy were calculated in each sliding window. Finally, machine learning models were utilized to predict the seizure onset zone (SOZ) and undergo performance evaluation.</div></div><div><h3>Results</h3><div>The MI and inflow intensity of SOZ in each frequency band were significantly higher (<em>p</em> &lt; 0.001) than those of nSOZ, and exhibited an initial increase followed by a decrease after onset. The outflow intensity and sample entropy (except delta band) of SOZ were significantly lower (<em>p</em> &lt; 0.001) than those of nSOZ, which rose first and then fell after onset. The features of the propagation zone lay between those of the SOZ and non-involved zone. Integrating these features with machine learning models effectively localized SOZ, among which XGBoost model had the best performance, its AUC, accuracy, specificity, and sensitivity, and were 0.905, 87.0 %, 87.9 %, and 79.5 % respectively.</div></div><div><h3>Conclusions</h3><div>This study explored the dynamic evolution during the peri-ictal period from multiple perspectives. There were strong control effects both inside and outside the SOZ before seizure onset but decreased later, confirming the existence of regulatory mechanism of seizures. Further subdivision revealed a hierarchical organization of the regulatory model. Combined with machine learning models, multiple features accurately localized the SOZ, providing a new sight for clinical treatment and serving as a reference model.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106998"},"PeriodicalIF":5.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255163","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":"TIMP1 inhibits Rac1-mediated ROS production to ameliorate blood–spinal cord barrier disruption in amyotrophic lateral sclerosis","authors":"Jingshu Tang,&nbsp;Yuying Kang,&nbsp;Qiuyu Chen,&nbsp;Baodan Zhang,&nbsp;Nianying Shang,&nbsp;Jiaqi Lan,&nbsp;Lei Wu,&nbsp;Ying Peng","doi":"10.1016/j.nbd.2025.106987","DOIUrl":"10.1016/j.nbd.2025.106987","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons, for which therapeutic strategies and pharmacological interventions remain limited. Disruption of the blood–spinal cord barrier (BSCB) has been identified as a significant factor that may exacerbate motor neuron damage. Tissue inhibitor of metalloproteinase-1 (TIMP1), a molecule known for its dual roles in inhibiting matrix metalloproteinase (MMP) activity and exerting cytokine-like effects via receptor interactions, has been demonstrated to ameliorate endothelial barrier damage in various diseases. Here, we explored the potential of TIMP1 to restore BSCB integrity as a strategy to slow the ALS progression. Specifically, the expression of TIMP1 or its mutant variant AlaTIMP1, which lacks MMP-inhibitory activity, in spinal cord microvascular endothelial cells (SCMECs) prior to disease onset significantly reduces BSCB leakage in mice with ALS, thereby alleviating motor function deficits and delaying disease progression. Additionally, TIMP1 expression restores the expression of junctional complexes in SCMECs, as demonstrated in both in vivo and in vitro ALS models. Mechanistic studies revealed that TIMP1 suppresses ALS injury-induced integrin β1 activation independent of MMP inhibition, blocking downstream Rac1 translocation to the membrane to form a complex with NOX2. The inhibition of NOX2 activity reduces ROS-induced cytoskeletal remodeling, consequently stabilizing overall junctional alignment and preserving the BSCB integrity. Overall, our findings elucidate an MMP-independent mechanism through which TIMP1 regulates BSCB integrity in ALS context, suggesting that TIMP1 could serve as a novel tool for the treatment of ALS, particularly for prophylactic treatment in patients with familial ALS.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106987"},"PeriodicalIF":5.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280693","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":"Modulation of miR-145 in a mouse model of multiple sclerosis: A promising approach to attenuate inflammation and degeneration","authors":"Monique Marylin Alves de Almeida ,&nbsp;Samantha F. Kornfeld ,&nbsp;Yves De Repentigny ,&nbsp;Majd Al-Aarg ,&nbsp;Ibrahim Ghani ,&nbsp;Sarah E. Cummings ,&nbsp;Emma R. Sutton ,&nbsp;Rebecca Yaworski ,&nbsp;Kelsea S. McKay ,&nbsp;Sabrina Gagnon ,&nbsp;Ariane Beauvais ,&nbsp;Rashmi Kothary","doi":"10.1016/j.nbd.2025.106999","DOIUrl":"10.1016/j.nbd.2025.106999","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system (CNS) marked by myelin loss, which impairs nerve function. Current therapies fail to halt disease progression or prevent myelin and axonal degeneration. In this study, we explored the impact of miR-145 loss in a murine model of experimental autoimmune encephalomyelitis (EAE), which mimics MS pathology. Loss of miR-145 reduced clinical severity and significantly decreased immune cell infiltration in the lumbar spinal cord during both the onset and chronic stages of the disease. Additionally, miR-145 loss altered the expression of key inflammatory genes and modulated astrocytic activity throughout EAE. Of significant interest, acute treatment with an antisense oligonucleotide (ASO) targeting miR-145 decreased miR-145 levels and led to reduced disease severity, decreased immune cell infiltration, and an increase in regulatory T cells in EAE mice. Moreover, miR-145 deficiency mitigated axon and myelin degeneration. Our findings suggest that ASOs targeting miR-145 may offer a promising therapeutic strategy, addressing both inflammatory and degenerative components of MS.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106999"},"PeriodicalIF":5.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279787","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":"Early and widespread cerebellar engagement during hippocampal seizures and interictal discharges","authors":"M.L. Streng ,&nbsp;B.W. Kottke ,&nbsp;E.M. Wasserman ,&nbsp;L. Zecker ,&nbsp;L. Luong ,&nbsp;S. Kodandaramaiah ,&nbsp;T.J. Ebner ,&nbsp;E. Krook-Magnuson","doi":"10.1016/j.nbd.2025.106991","DOIUrl":"10.1016/j.nbd.2025.106991","url":null,"abstract":"<div><div>Despite research illustrating the cerebellum may be a critical circuit element in processes beyond motor control, and growing evidence for a role of the cerebellum in a range of neurological disorders, including the epilepsies, remarkably little is known about cerebellar changes during seizures. We therefore implemented a novel method for repeated widefield calcium imaging of the cerebellum in awake, chronically epileptic mice. We found widespread changes in cerebellar Purkinje cell activity during temporal lobe seizures. Changes were noted in the anterior and posterior cerebellum (lobules IV-VII), along the midline (vermis), and both ipsilaterally and contralaterally (in the simplex and Crus I) to the seizure focus. This was true for both overtly behavioral seizures <em>and</em> for hippocampal seizures that remained electrographic only – arguing against cerebellar modulation simply reflecting motor components. Moreover, even brief interictal spikes produced widespread alterations in cerebellar activity. Perhaps most remarkably, changes in the cerebellum also occurred <em>prior</em> to any noticeable change in the hippocampal electrographic recordings. Together these results underscore the relevance of the cerebellum with respect to seizure networks, warranting a more consistent consideration of the cerebellum in epilepsy.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106991"},"PeriodicalIF":5.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264012","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":"Lessons from the Tim Greenamyre model","authors":"Laurie H. Sanders ,&nbsp;Nancy Blechman ,&nbsp;Sarah Berman ,&nbsp;Erwan Bezard ,&nbsp;Fabio Blandini ,&nbsp;Jason Cannon ,&nbsp;Mark Cookson ,&nbsp;Briana De Miranda ,&nbsp;Roberto Di Maio ,&nbsp;Robert Drolet ,&nbsp;Jim Greene ,&nbsp;Jessica Kappel ,&nbsp;Mark Kaufmann ,&nbsp;Matthew Keeney ,&nbsp;Arthur S. Levine ,&nbsp;Abby Olsen ,&nbsp;Teddy Pettus ,&nbsp;Sean Pintchovski ,&nbsp;Ian Reynolds ,&nbsp;Emily Rocha ,&nbsp;Pier Mastroberardino","doi":"10.1016/j.nbd.2025.106995","DOIUrl":"10.1016/j.nbd.2025.106995","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106995"},"PeriodicalIF":5.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275406","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":"Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity","authors":"Andrea Mancini ,&nbsp;Laura Bellingacci ,&nbsp;Jacopo Canonichesi ,&nbsp;Miriam Sciaccaluga ,&nbsp;Alfredo Megaro ,&nbsp;Elisa Zianni ,&nbsp;Maria De Carluccio ,&nbsp;Marilena Pariano ,&nbsp;Edoardo Emiliano ,&nbsp;Alessandro Tozzi ,&nbsp;Cinzia Costa ,&nbsp;Teresa Zelante ,&nbsp;Luigina Romani ,&nbsp;Maria Teresa Viscomi ,&nbsp;Fabrizio Gardoni ,&nbsp;Paolo Calabresi ,&nbsp;Lucilla Parnetti ,&nbsp;Massimiliano Di Filippo","doi":"10.1016/j.nbd.2025.106994","DOIUrl":"10.1016/j.nbd.2025.106994","url":null,"abstract":"<div><div>The basal ganglia (BG) network exerts a key role in the integration of cortical inputs and is fundamental to motor learning, behavior, emotional responses, and cognitive functions. Little is known about how immune cells and soluble immune mediators influence BG activity. Interleukin-17A (IL-17A) is in the spotlight for its emerging role as a neuromodulator of cortical synaptic transmission and plasticity in physiological and pathological conditions. However, its role at the level of subcortical structures such as the BG circuit is still unclear. In this study, we demonstrate that striatal medium spiny neurons (MSNs) highly express IL-17RA and that the IL-17 axis contributes to the physiological expression of synaptic plasticity in these cells. Indeed, long-term potentiation (LTP) induction was significantly reduced in mice lacking IL-17A or IL-17RA. This effect might rely on an altered glutamatergic transmission, as synaptic expression of NMDAR subunit GluN2B is reduced in mice lacking IL-17A. At the same time, exposure to high concentrations of IL-17A was found to impair LTP induction through modulation of NMDAR currents. These results suggest a dual effect of this cytokine on striatal synaptic plasticity, showing the IL-17 axis as a key neuromodulator of the BG circuit, with potential implications in the pathogenesis of neuroinflammatory and neuropsychiatric disorders.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106994"},"PeriodicalIF":5.1,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266809","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":"ANKK1, ANKRD50, GRK5, PACSIN1 and VPS8 are novel candidate genes associated with late onset Parkinson's disease: Definition of a novel predictive protocol based on polygenic model of inheritance","authors":"Federica Carrillo ,&nbsp;Nicole Piera Palomba ,&nbsp;Sara Pietracupa ,&nbsp;Laura Ianiro ,&nbsp;Giorgio Fortunato ,&nbsp;Margherita Degasperi ,&nbsp;Tiziana Giloni ,&nbsp;Maria Ilenia De Bartolo ,&nbsp;Luigi Pavone ,&nbsp;Teresa Nutile ,&nbsp;Nicola Modugno ,&nbsp;Danilo Licastro ,&nbsp;Teresa Esposito","doi":"10.1016/j.nbd.2025.106996","DOIUrl":"10.1016/j.nbd.2025.106996","url":null,"abstract":"<div><div>Parkinson's disease (PD) represents one of the most frequent neurodegenerative disorders for which genetic diagnosis is still challenging due to the high genetic heterogeneity associated with the disease and to the difficulty in interpreting test results. We have recently reported the identification of rare new gene variants in PD patients that support polygenic contribution to the disease. Here we report the identification of novel candidate PD genes and an exploratory protocol for predictive analysis of PD risk.</div><div>The study includes the whole exome data of 22 PD families, 300 unrelated familiar PD, 504 unrelated sporadic PD and 664 healthy subjects. Family-based approach identified rare and disrupting variants in 44 candidate PD genes co-inherited by affected relatives. The analysis of the entire cohort discovered a significant excess of rare and deleterious variants in PD patients compared to controls in 7 genes out of the 44 identified in the families. Five of these, known as <em>ANKK1, ANKRD50, GRK5, PACSIN1</em> and <em>VPS8,</em> were novel candidate PD genes, expressed in human dopaminergic neurons, and involved in signal transduction pathways and in endocytic recycling. In these genes, we identified both rare probably damaging variants, altering protein structure and dynamics, as well as frequent variants associated with PD risk. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in a panel of 37 PD genes selected in this study, may predict disease risk in about 26 % of patients, both familial and sporadic cases, with high specificity (&gt; 92 %; <em>p</em> ≤0.00001). Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment (<em>p</em> = 0.004), severe cognitive impairment (<em>p</em> = 0.009) and an earlier age at onset of the disease (<em>p</em> = 0.01). Despite the still exploratory nature of the study, these data provide novel insights into the genetic of PD and may be relevant for its prediction, diagnosis and treatment.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106996"},"PeriodicalIF":5.1,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255162","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":"Inhibitory circuit dysfunction as a potential contributor to cortical reorganization in Glioblastoma progression","authors":"Cristina Spalletti ,&nbsp;Marta Scalera ,&nbsp;Elisabetta Mori ,&nbsp;Sabrin Haddad ,&nbsp;Marco Mainardi ,&nbsp;Daniele Cangi ,&nbsp;Vinoshene Pillai ,&nbsp;Elena Parmigiani ,&nbsp;Silvia Landi ,&nbsp;Matteo Caleo ,&nbsp;Eleonora Vannini","doi":"10.1016/j.nbd.2025.106997","DOIUrl":"10.1016/j.nbd.2025.106997","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly aggressive brain tumor that infiltrates surrounding brain tissue, profoundly affecting adjacent cortical areas. This study investigates how GBM reshapes the peritumoral cortex by examining plasticity changes in two GBM mouse models. Using optogenetic stimulation, we observed altered motor mapping and reduced cortical specificity in GBM mice compared to controls. Morphologically, GBM mice showed a reduction in dendritic spines, perineuronal nets, and inhibitory markers. Functionally, inhibitory circuits were markedly impaired, characterized by an increased frequency of spontaneous inhibitory currents and a decrease in their amplitude. Our findings highlight the critical role of inhibitory circuit disruption in driving cortical reorganization and loss of motor map specificity. The reduction of parvalbumin and somatostatin interneurons, degradation of perineuronal nets, and imbalance in the excitation/inhibition ratio contribute to maladaptive plasticity, increasing the risk of hyperexcitability and seizures. These insights offer a basis for developing therapeutic strategies aimed at restoring inhibitory function, mitigating GBM-induced cortical changes, and potentially improving patient outcomes.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 106997"},"PeriodicalIF":5.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258525","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}