Neuropathology and Applied Neurobiology最新文献

{"title":"Effects of mutant huntingtin in oxytocin neurons on non-motor features of Huntington's disease.","authors":"Sofia Bergh,&nbsp;Sanaz Gabery,&nbsp;Simone Tonetto,&nbsp;Deniz Kirik,&nbsp;Åsa Petersén,&nbsp;Rachel Y Cheong","doi":"10.1111/nan.12891","DOIUrl":"https://doi.org/10.1111/nan.12891","url":null,"abstract":"<p><strong>Background: </strong>Early non-motor features including anxiety, depression and altered social cognition are present in Huntington's disease (HD). The underlying neurobiological mechanisms are not known. Oxytocin (OXT) is involved in the regulation of emotion, social cognition and metabolism, and our previous work showed that the OXT system is affected early in HD. The aim of the study was to investigate the potential causal relationship between the selective expression of mutant huntingtin (mHTT) in OXT neurons and the development of non-motor features and neuropathology.</p><p><strong>Methods: </strong>To express mHTT only in OXT neurons, we used a novel flex-switch adeno-associated viral vector design to selectively express either mHTT or wild-type HTT in the paraventricular nucleus of the hypothalamus using OXT-Cre-recombinase mice. We also performed a mirror experiment to selectively delete mHTT in OXT neurons using the BACHD mouse model. Mice underwent a battery of behavioural tests to assess psychiatric and social behaviours 3 months post-injection or at 2 months of age, respectively. Post-mortem analyses were performed to assess the effects on the OXT system.</p><p><strong>Results: </strong>Our results show that selective expression of mHTT in OXT neurons was associated with the formation of mHTT inclusions and a 26% reduction of OXT-immunopositive neurons as well as increased anxiety-like behaviours compared with uninjected mice. However, selective deletion of mHTT from OXT neurons alone was not sufficient to alter the metabolic and psychiatric phenotype of the BACHD mice at this early time point.</p><p><strong>Conclusions: </strong>Our results indicate that mHTT expression can exert cell-autonomous toxic effects on OXT neurons without affecting the non-motor phenotype at early time points in mice.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12891"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690407","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":"Issue Information","authors":"","doi":"10.1111/nan.12823","DOIUrl":"https://doi.org/10.1111/nan.12823","url":null,"abstract":"No abstract is available for this article.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43159077","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":"Occurrence of focal myositis during Behçet's disease: The identification of a specific vasculitis-associated focal myopathy.","authors":"Laure Gallay,&nbsp;Arnaud Hot,&nbsp;Yves Allenbach,&nbsp;Delphine Maucort-Boulch,&nbsp;Cloe Comarmond,&nbsp;Cindy Marques,&nbsp;Laurent Perard,&nbsp;Anne Simon,&nbsp;Kuberaka Mariampillai,&nbsp;Patrice Cacoub,&nbsp;Laure Mery-Bossard,&nbsp;Pascal Cathebras,&nbsp;Leonard Feasson,&nbsp;Alice Berezne,&nbsp;Chafika Morati,&nbsp;Lola Lessard,&nbsp;Marie Faruch,&nbsp;Nathalie Streichenberger,&nbsp;David Saadoun","doi":"10.1111/nan.12900","DOIUrl":"https://doi.org/10.1111/nan.12900","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association.</p><p><strong>Methods: </strong>This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD - FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed.</p><p><strong>Results: </strong>The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16-35] years, and at FM diagnosis, it was 30 [26-42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare-ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD - FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042).</p><p><strong>Conclusions: </strong>FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis-associated focal myopathy with a specific clinico-histological pattern. Patients with this association require long-term follow-up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12900"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9366556","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":"Cover Image, Volume 49, Issue 2","authors":"Chia-Wei Huang, Kuang-Yung Lee, Peng-Tzu Lin, Fang-Shin Nian, Haw-Yuan Cheng, Chien-Hui Chang, Cheng-Yen Liao, Yen-Lin Su, Carol Seah, Ching Li, Yu-Fu Chen, Mei-Hsuan Lee, Jin-Wu Tsai","doi":"10.1111/nan.12901","DOIUrl":"https://doi.org/10.1111/nan.12901","url":null,"abstract":"The cover image is based on the Original Article <i>Muscleblind-Like 2 knockout shifts adducin 1 isoform expression and alters dendritic spine dynamics of cortical neurons during brain development</i> by Chia-Wei Huang et al., https://doi.org/10.1111/nan.12890.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"18 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138515864","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":"124th Meeting of the British Neuropathological Society The View, Royal College of Surgeons of England, Lincoln's Inn Fields, London","authors":"Z. Jaunmuktane, Sebastian, Brandner, G. Cruickshank","doi":"10.1111/nan.12881","DOIUrl":"https://doi.org/10.1111/nan.12881","url":null,"abstract":"SESSION I Chair: Caroline Sewry, RJAH Orthopaedic Hospital, Salford Royal Hospital & UCL-GOSH Dubowitz Neuromuscular Centre, UK 13:05–13:35 Muscle cell fusion during disease and opportunities for therapies Doug Millay, Cincinnati Children’s Hospital Medical Center, USA 13:35–14:05 The transcription factor Nfix in skeletal muscle development and muscular dystrophies Graziella Messina, University of Milan, Italy 14:05–14:35 Mechanisms of muscle mass regulation in health and disease Marco Sandri, University of Padova, Italy 14:35–15:00 Coffee break","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41697387","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":"Poster Abstracts","authors":"","doi":"10.1111/nan.12883","DOIUrl":"https://doi.org/10.1111/nan.12883","url":null,"abstract":"","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135947669","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":"Rapid bacterial identification from formalin-fixed paraffin-embedded neuropathology specimens using 16S rDNA nanopore sequencing.","authors":"Anne Albers,&nbsp;Dorothee Cäcilia Spille,&nbsp;Eric Suero-Molina,&nbsp;Frieder Schaumburg,&nbsp;Walter Stummer,&nbsp;Werner Paulus,&nbsp;Christian Thomas","doi":"10.1111/nan.12871","DOIUrl":"https://doi.org/10.1111/nan.12871","url":null,"abstract":"Bacterial infections of the central nervous system (CNS) can be severe, life-threatening diseases. Early detection of causative pathogens is crucial for the rapid administration of a tailored antibiotic regime. However, microbiological cultures are negative in one third of bacterial CNS abscesses [1], and routine neuropathology diagnostics are typically limited to histological staining techniques such as Gram or Warthin-Starry. Moreover, tissue might not have been submitted for microbiological culture at the time of surgery in cases without a preoperative suspicion of CNS infection. Molecular diagnostics using pathogen-specific PCR provides an alternative diagnostic approach and has been successfully applied to formalin-fixed paraffinembedded (FFPE) tissue samples [2] but is hypothesis driven and thus requires a priori suspicion of the causative pathogen. Metagenomic sequencing of the bacterial 16S rRNA gene represents an unbiased alternative and has been successfully applied to study the bacterial metagenome of brain abscesses based on DNA extracted from unfixed specimens [3, 4]. Here, we introduce a rapid and scalable approach for bacterial pathogen detection from FFPE specimens using nanopore sequencing of 16S rDNA amplicons. FFPE samples of 32 bacterial CNS infections (31 brain abscesses and 1 subdural empyema) and 3 control samples (reactive brain tissue) were retrieved from our archive. Clinical data and microbiological culture results were compiled by reviewing patient records. After DNA extraction, multiplex PCR with four primer sets covering variable regions 3–7 of the 16S rRNA gene was performed (see the supporting information). PCR products were sequenced on a nanopore Mk1c device. After basecalling, raw fastq files were uploaded on the EPI2ME platform (Metrichor Ltd., Oxford, UK), and results were loaded into the R environment for further analysis (supporting information). Raw sequencing files are available under the BioProject Accession No. PRJNA899355 (ncbi.nlm.nih.gov/bioproject/899355). The median age of the 8 females and 24 males was 57 years (range 13–84 years). Preoperatively, a diagnosis of bacterial CNS infection has been suspected in 24 patients (75%), whereas a malignant tumour was radiologically considered in six cases (19%); in two patients, the aetiology of the lesion had been unclear (Table S1). On Gram staining, bacteria were identified in 23 samples (72%). All cases had positive bacterial cultures, and 10 samples (31%) showed mixed infections with up to three taxa. Deep 16S rDNA nanopore sequencing yielded 31,706 classifiable reads per sample (median, interquartile range: 18,255–40,901). To control for potential sources of contamination, we additionally sequenced four no-template PCR controls (NTC) and three reactive brain tissue samples (median depth: 27,077 reads). Taxonomic classification of the controls revealed Brachybacterium, Brevundimonas and Bradyrhizobium as the most prevalent genera accounting for &gt;90% of r","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 1","pages":"e12871"},"PeriodicalIF":5.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9361618","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":"A non-hemispheric transtentorial ZFTA fusion-positive ependymoma in a 6-month-old boy.","authors":"Antonello Cardoni,&nbsp;Sabina Barresi,&nbsp;Eleonora Piccirilli,&nbsp;Viola Alesi,&nbsp;Evelina Miele,&nbsp;Isabella Giovannoni,&nbsp;Silvia Genovese,&nbsp;Giada Del Baldo,&nbsp;Francesca Diomedi-Camassei,&nbsp;Manila Antonelli,&nbsp;Felice Giangaspero,&nbsp;Chiara Puggioni,&nbsp;Andrea Carai,&nbsp;Giovanna Stefania Colafati,&nbsp;Angela Mastronuzzi,&nbsp;Marco Gessi,&nbsp;Rita Alaggio,&nbsp;Sabrina Rossi","doi":"10.1111/nan.12886","DOIUrl":"https://doi.org/10.1111/nan.12886","url":null,"abstract":"Pathology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Imaging Department, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Department of Neuroscience, Imaging and Clinical Sciences (DNISC), University “Gabriele D’Annunzio” of Chieti-Pescara, Chieti, Italy Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Department of Onco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Department of Radiology, Oncology and Anatomic Pathology, University La Sapienza, Rome, Italy IRCCS Neuromed, Pozzilli, Italy Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Neuropathology Unit, Pathology Division Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica S. Cuore, Rome, Italy","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 1","pages":"e12886"},"PeriodicalIF":5.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10855887","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":"Unveiling the identities of null cell tumours: Epigenomics corroborate subtle histological cues in pituitary neuroendocrine tumour/adenoma classification.","authors":"Matthias Dottermusch,&nbsp;Ulrich Schüller,&nbsp;Christian Hagel,&nbsp;Wolfgang Saeger","doi":"10.1111/nan.12870","DOIUrl":"https://doi.org/10.1111/nan.12870","url":null,"abstract":"<p><strong>Aims: </strong>Pituitary neuroendocrine tumour (PitNET)/adenoma classification is based on cell lineage and requires immunopositivity for adenohypophysial hormones and/or transcription factors (TFs) steroidogenic factor 1 (SF1), T-box transcription factor TBX19 (TPIT) or pituitary-specific positive transcription factor 1 (PIT1). PitNET/adenomas lacking lineage affiliation are termed 'null cell' tumours (NCTs). NCT diagnosis may be afflicted by methodological limitations and inconsistent diagnostic approaches. Previous studies have questioned the existence of true NCTs. In this study, we explore the epigenomic identities of PitNET/adenomas lacking clear TF immunopositivity.</p><p><strong>Methods: </strong>Seventy-four hormone-negative PitNET/adenomas were immunostained and scored for SF1, TPIT and PIT1 expression. All tumours were classified as gonadotroph, corticotroph, PIT1-positive or 'null cell'. NCTs were subjected to global DNA methylation analysis. Epigenomic profiles of NCTs were compared to reference tumours using Uniform Manifold Approximation and Projection (UMAP) plotting and methylation-based classification.</p><p><strong>Results: </strong>TF immunostaining revealed definite lineage identity in 59 of 74 (79.7%) hormone-negative PitNET/adenomas. Of the remaining 15 NCTs, 13 demonstrated minimal and inconclusive nuclear SF1 or TPIT expression (5 and 8, respectively). Two NCTs were entirely immunonegative. UMAP plotting and methylation-based classification demonstrated that the epigenomes of NCTs with minimal SF1 or TPIT expression were adequately affiliated with gonadotroph or corticotroph lineages, respectively. The two immunonegative NCTs were located near the corticotroph PitNET/adenomas via UMAP, whereas the methylation classifier could not match these two cases to predefined tumour classes.</p><p><strong>Conclusions: </strong>Epigenomic analyses substantiate lineage identification based on minimal TF immunopositivity in PitNET/adenomas. This strategy dramatically decreases the incidence of NCTs and further challenges the legitimacy of NCTs as a distinct PitNET/adenoma subtype. Our study may be useful for guiding diagnostic efforts and future considerations of PitNET/adenoma classification.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 1","pages":"e12870"},"PeriodicalIF":5.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10794425","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":"Robust methylation-based classification of brain tumours using nanopore sequencing.","authors":"Luis P Kuschel,&nbsp;Jürgen Hench,&nbsp;Stephan Frank,&nbsp;Ivana Bratic Hench,&nbsp;Elodie Girard,&nbsp;Maud Blanluet,&nbsp;Julien Masliah-Planchon,&nbsp;Martin Misch,&nbsp;Julia Onken,&nbsp;Marcus Czabanka,&nbsp;Dongsheng Yuan,&nbsp;Sören Lukassen,&nbsp;Philipp Karau,&nbsp;Naveed Ishaque,&nbsp;Elisabeth G Hain,&nbsp;Frank Heppner,&nbsp;Ahmed Idbaih,&nbsp;Nikolaus Behr,&nbsp;Christoph Harms,&nbsp;David Capper,&nbsp;Philipp Euskirchen","doi":"10.1111/nan.12856","DOIUrl":"https://doi.org/10.1111/nan.12856","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation-based classification of cancer provides a comprehensive molecular approach to diagnose tumours. In fact, DNA methylation profiling of human brain tumours already profoundly impacts clinical neuro-oncology. However, current implementation using hybridisation microarrays is time consuming and costly. We recently reported on shallow nanopore whole-genome sequencing for rapid and cost-effective generation of genome-wide 5-methylcytosine profiles as input to supervised classification. Here, we demonstrate that this approach allows us to discriminate a wide spectrum of primary brain tumours.</p><p><strong>Results: </strong>Using public reference data of 82 distinct tumour entities, we performed nanopore genome sequencing on 382 tissue samples covering 46 brain tumour (sub)types. Using bootstrap sampling in a cohort of 55 cases, we found that a minimum set of 1000 random CpG features is sufficient for high-confidence classification by ad hoc random forests. We implemented score recalibration as a confidence measure for interpretation in a clinical context and empirically determined a platform-specific threshold in a randomly sampled discovery cohort (N = 185). Applying this cut-off to an independent validation series (n = 184) yielded 148 classifiable cases (sensitivity 80.4%) and demonstrated 100% specificity. Cross-lab validation demonstrated robustness with concordant results across four laboratories in 10/11 (90.9%) cases. In a prospective benchmarking (N = 15), the median time to results was 21.1 h.</p><p><strong>Conclusions: </strong>In conclusion, nanopore sequencing allows robust and rapid methylation-based classification across the full spectrum of brain tumours. Platform-specific confidence scores facilitate clinical implementation for which prospective evaluation is warranted and ongoing.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 1","pages":"e12856"},"PeriodicalIF":5.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10798152","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}