Brain最新文献

{"title":"Responses to 'On the responsibilities of intellectuals and the rise of bullshit jobs in universities'.","authors":"Masud Husain","doi":"10.1093/brain/awaf141","DOIUrl":"https://doi.org/10.1093/brain/awaf141","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"148 5","pages":"e48-e49"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural history of Becker muscular dystrophy: DMD gene mutations predict clinical severity.","authors":"Domenico Gorgoglione, Daniele Sabbatini, Pietro Riguzzi, Giuliana Capece, Marika Pane, Serenella Servidei, Marta Briganti, Cristina Sancricca, Fabio Bruschi, Anna Ardissone, Riccardo Masson, Annamaria Gallone, Lorenzo Maggi, Esther Picillo, Luisa Politano, Angela Petrosino, Sara Vianello, Martina Penzo, Matteo Villa, Maria Sframeli, Cosimo Allegra, Andrea Barp, Alessandra Di Bari, Francesca Salmin, Emilio Albamonte, Giovanni Colacicco, Chiara Panicucci, Monica Traverso, Concetta Palermo, Alberto Lerario, Daniele Velardo, Maria G D'Angelo, Angela Berardinelli, Alice Gardani, Roberta Nicotra, Stefano Parravicini, Gabriele Siciliano, Giulia Ricci, Francesca Torri, Giulio Gadaleta, Guido Urbano, Enrica Rolle, Federica Ricci, Adele D'Amico, Michela Catteruccia, Antonella Pini, Melania Giannotta, Roberta Battini, Gemma Marinella, Stefano C Previtali, Alberto A Zambon, Alessandra Ferlini, Fernanda Fortunato, Francesca Magri, Tiziana E Mongini, Valeria A Sansone, Claudio Bruno, Sonia Messina, Vincenzo Nigro, Isabella Moroni, Eugenio Mercuri, Luca Bello, Elena Pegoraro","doi":"10.1093/brain/awae358","DOIUrl":"10.1093/brain/awae358","url":null,"abstract":"<p><p>Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease attributable to mutations in DMD, leading to a deficient and less functional dystrophin, mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments. Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centres. Patients' demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation, cardiac left ventricular ejection fraction, pulmonary forced vital capacity and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups. The median age at the last assessment was 26.0 (16.6-41.9) years, with a median age at diagnosis of 7.5 (4.0-14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKaemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan-Meier analysis of 69 years. Thirty per cent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten per cent of patients carried out-of-frame mutations, 4% nonsense mutations and 86% in-frame deletions/duplications. The subset of in-frame deletions was classified further based on the specific mutations. Patients carrying del45-49 compared with del45-47 were associated with an earlier loss of ambulation (P = 1 × 10-4), whereas patients with del45-55 (P = 0.005), del48 (P = 0.02) and del48-49 (P = 0.02) were correlated with a later loss of ambulation compared with del45-47. Both del45-55 (P = 0.002) and del48 (P = 0.003) were significantly associated with decreased odds of developing a pathological left ventricular ejection fraction compared with del45-47. Our results contribute to a better understanding of the natural history of BMD and capture precious data in the era of emerging therapies. The knowledge of the specific DMD mutation might help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1695-1706"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Converging cross-modal evidence for a phylogenetic age effect in neurodegenerative susceptibility.","authors":"Laura Iris Van Hove, François-Laurent De Winter, Qi Zhu, Gert Cypers, Wim Vanduffel, Beatrice de Gelder, Mathieu Vandenbulcke, Jan Van den Stock","doi":"10.1093/brain/awaf050","DOIUrl":"10.1093/brain/awaf050","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e34-e36"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor PPARγ targets GPNMB to promote oligodendrocyte development and remyelination.","authors":"Bing Han, Ming-Yue Bao, Qing-Qing Sun, Rui-Ning Wang, Xin Deng, Kun Xing, Feng-Lin Yu, Yan Zhang, Yue-Bo Li, Xiu-Qing Li, Na-Nan Chai, Gai-Xin Ma, Ya-Na Yang, Meng-Yuan Tian, Qian Zhang, Xing Li, Yuan Zhang","doi":"10.1093/brain/awae378","DOIUrl":"10.1093/brain/awae378","url":null,"abstract":"<p><p>Myelin injury occurs in brain ageing and in several neurological diseases. Failure of spontaneous remyelination is attributable to insufficient differentiation of oligodendrocyte precursor cells (OPCs) into mature myelin-forming oligodendrocytes in CNS demyelinated lesions. Emerging evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) is the master gatekeeper of CNS injury and repair and plays an important regulatory role in various neurodegenerative diseases. Although studies demonstrate positive effects of PPARγ in oligodendrocyte ontogeny in vitro, the cell-intrinsic role of PPARγ and the molecular mechanisms involved in the processes of OPC development and CNS remyelination in vivo are poorly understood. Here, we identify PPARγ as an enriched transcription factor in the dysfunctional OPCs accumulated in CNS demyelinated lesions. Its expression increases during OPC differentiation and myelination and is closely related to the process of CNS demyelination/remyelination. Administration of pharmacological agonists of PPARγ not only promotes OPC differentiation and CNS myelination, but also causes a significant increase in remyelination in both cuprizone- and lysophosphatidylcholine-induced demyelination models. In contrast, the attenuation of PPARγ function, either through the specific knockout of PPARγ in oligodendrocytes in vivo or through its inhibition in vitro, leads to decreased OPC maturation, hindered myelin generation and reduced therapeutic efficacy of PPARγ agonists. At a mechanistic level, PPARγ induces myelin repair by directly targeting glycoprotein non-metastatic melanoma protein B (GPNMB), a novel regulator that drives OPCs to differentiate into oligodendrocytes, promotes myelinogenesis in the developing CNS of postnatal mice and enhances remyelination in mice with lysophosphatidylcholine-induced demyelination. In conclusion, our evidence reveals that PPARγ is a positive regulator of endogenous OPC differentiation and CNS myelination/remyelination and suggests that PPARγ and/or its downstream sensor (GPNMB) might be a candidate pharmacological target for regenerative therapy in the CNS.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1801-1816"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming the dopamine-centric model of impulse control disorders in Parkinson’s disease: the role of 5-HT","authors":"Roberto Cilia, Valtteri Kaasinen","doi":"10.1093/brain/awaf145","DOIUrl":"https://doi.org/10.1093/brain/awaf145","url":null,"abstract":"This scientific commentary refers to ‘Serotonergic dysfunction in patients with impulse control disorders in Parkinson’s disease’ by Prange et al. (https://doi.org/10.1093/brain/awaf087).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"57 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Against the moral hemiplegia of the intellectual class.","authors":"José Alberto González Cáceres","doi":"10.1093/brain/awaf138","DOIUrl":"https://doi.org/10.1093/brain/awaf138","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"29 1","pages":"e41-e42"},"PeriodicalIF":14.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yes, the human brain has around 86 billion neurons.","authors":"Roberto Lent","doi":"10.1093/brain/awaf048","DOIUrl":"10.1093/brain/awaf048","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"e37-e38"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental health disorders before, during and after the COVID-19 pandemic: a nationwide study.","authors":"Clara S Grønkjær, Rune H B Christensen, Daniel Kondziella, Michael E Benros","doi":"10.1093/brain/awae360","DOIUrl":"10.1093/brain/awae360","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic and lockdowns prompted a major concern for mental health effects. Comprehensive nationwide studies are lacking on the indirect effect of the COVID-19 pandemic on the mental health of the population. We aimed to determine whether the COVID-19 pandemic and lockdowns affected mental health service usage, suicide attempts and suicides. This comprehensive nationwide register-linked study followed all individuals in Denmark from 1990. The main outcomes were rates of psychiatric admissions, use of psychotropic medication, suicide attempts, suicides, patients in community-based private psychiatry or psychology practices and referrals to psychiatric hospitals. The impact of the pandemic (11 March 2020-30 June 2023) and lockdowns was assessed with log-normal models adjusted for pre-pandemic trends (1 January 2017-10 March 2020). We reported rate ratios (RR) of the observed and counterfactual rates. We identified the 5 807 714 (50.3% female) individuals living in Denmark on 1 March 2020. The rates of psychiatric admissions [RR: 0.95, 95% confidence interval (CI): 0.91 to 0.99, P-value: 0.017] and suicide attempts (RR: 0.85, 95% CI: 0.76 to 0.95, P-value: 0.007) were lower during the pandemic compared with the pre-pandemic trend. The rates of suicides (RR: 0.89, 95% CI: 0.75-1.05, P-value: 0.173), patients in private practices (RR: 1.00, 95% CI: 0.96-1.04, P-value: 0.986) and referrals (RR: 1.06, 95% CI: 0.95-1.18, P-value: 0.307) were not significantly different during the pandemic compared with the pre-pandemic trend. During the first lockdown, rates were lower for psychiatric admissions (RR: 0.85, 95% CI: 0.80 to 0.90, P-value <0.001), suicide attempts (RR: 0.80, 95% CI: 0.69 to 0.94, P-value: 0.007), suicides (RR: 0.67, 95% CI: 0.52 to 0.86, P-value: 0.002), patients in private practices (RR: 0.88, 95% CI: 0.82 to 0.93, P-value <0.001) and referrals (RR: 0.69, 95% CI: 0.60 to 0.81, P-value <0.001) compared with the pre-pandemic trend. However, during the pandemic, the rate of psychotropic medication users increased by 6% compared with the pre-pandemic trend (RR: 1.06, 95% CI: 1.05 to 1.06, P-value < 0.001). The COVID-19 pandemic and lockdowns did not severely influence pre-pandemic trends of the mental health burden in the population of Denmark on a nationwide level.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1829-1840"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.","authors":"Marnix Franken, Erik van der Wal, Dongxu Zheng, Bianca den Hamer, Patrick J van der Vliet, Richard J L F Lemmers, Anita van den Heuvel, Alexandra L Dorn, Cas G A Duivenvoorden, Stijn L M In 't Groen, Christian Freund, Bert Eussen, Rabi Tawil, Baziel G M van Engelen, W W M Pim Pijnappel, Silvère M van der Maarel, Jessica C de Greef","doi":"10.1093/brain/awae379","DOIUrl":"10.1093/brain/awae379","url":null,"abstract":"<p><p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the disease mechanism of FSHD and for development of FSHD therapy, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a 3D tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors from human induced pluripotent stem cells of three mosaic FSHD patients. 3D-TESMs derived from genetically affected myogenic progenitors recapitulated pathological features including DUX4 and DUX4 target gene expression, smaller myofibre diameters and reduced absolute forces upon electrical stimulation. RNA-sequencing data illustrated increased expression of DUX4 target genes in 3D-TESMs compared with 2D myotubes, and cellular differentiation was improved by 3D culture conditions. Treatment of 3D-TESMs with three different small molecules identified in drug development screens in 2D muscle cultures showed no improvements, and sometimes even declines, in contractile force and sarcomere organization. These results suggest that these compounds either have a detrimental effect on the formation of 3D-TESMs, an effect that might have been overlooked or was challenging to detect in 2D cultures and in vivo models, and/or that further development of the 3D-TESM model is needed. In conclusion, we have developed a 3D skeletal muscle model for FSHD that can be used for preclinical research focusing on DUX4 expression and downstream pathways of FSHD in relationship to contractile properties. In the future, we expect that this model can also be used for preclinical drug screening.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1723-1739"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reshaping computational neuropsychiatry beyond synaptopathy.","authors":"Hugo Bottemanne, Stephane Mouchabac, Christophe Gauld","doi":"10.1093/brain/awaf031","DOIUrl":"10.1093/brain/awaf031","url":null,"abstract":"<p><p>Computational neuropsychiatry is a leading discipline in explaining psychopathology in terms of neuronal message passing, distributed processing and belief propagation in neuronal networks. Active Inference (AI) is a way of representing this dysfunctional signal processing. According to the AI approach, all neuronal processing and action selection can be explained by maximizing Bayesian model evidence or minimizing variational free energy. Following these principles, it has been suggested that dysconnection in neuronal networks results in aberrant belief updating and erroneous inference, leading to psychiatric and neurologic symptoms. However, there is a classic distinction between disorders of inference (or synaptopathy-including the majority of psychiatric disorders) and disorders of brain function (including vascular neurological pathologies and severe forms of tauopathy and synucleinopathies). This distinction is generally based on the idea that synaptopathies impair neuromodulatory precision weighting, leading to rigid inferences or heightened sensitivity to noise, while disorders of brain function are linked to damage in the nervous system (disconnection). This makes it challenging to apply the logic of the free energy principle. We suggest that this distinction will enable future models of neuropsychiatric symptoms to be improved by considering more than neuronal message passing.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"1526-1530"},"PeriodicalIF":10.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}