Cristina Spalletti , Marta Scalera , Elisabetta Mori , Sabrin Haddad , Marco Mainardi , Daniele Cangi , Vinoshene Pillai , Elena Parmigiani , Silvia Landi , Matteo Caleo , Eleonora Vannini
{"title":"抑制回路功能障碍是胶质母细胞瘤进展中皮层重组的潜在因素。","authors":"Cristina Spalletti , Marta Scalera , Elisabetta Mori , Sabrin Haddad , Marco Mainardi , Daniele Cangi , Vinoshene Pillai , Elena Parmigiani , Silvia Landi , Matteo Caleo , Eleonora Vannini","doi":"10.1016/j.nbd.2025.106997","DOIUrl":null,"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":5.6000,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibitory circuit dysfunction as a potential contributor to cortical reorganization in Glioblastoma progression\",\"authors\":\"Cristina Spalletti , Marta Scalera , Elisabetta Mori , Sabrin Haddad , Marco Mainardi , Daniele Cangi , Vinoshene Pillai , Elena Parmigiani , Silvia Landi , Matteo Caleo , Eleonora Vannini\",\"doi\":\"10.1016/j.nbd.2025.106997\",\"DOIUrl\":null,\"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\":5.6000,\"publicationDate\":\"2025-06-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S096999612500213X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S096999612500213X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Inhibitory circuit dysfunction as a potential contributor to cortical reorganization in Glioblastoma progression
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.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.