Brain Pathology最新文献

{"title":"Two novel tumours with NTRK2 fusion in the methylation class of extraventricular neurocytomas, including one intraventricular","authors":"Emmanuelle Uro-Coste,&nbsp;Arnault Tauziede-Espariat,&nbsp;Charlotte Dubucs,&nbsp;Dan Christian Chiforeanu,&nbsp;Aurore Siegfried,&nbsp;Yvan Nicaise,&nbsp;Luc Bauchet,&nbsp;Laurent Riffaud,&nbsp;Franck Bielle,&nbsp;Alexandre Vasiljevic,&nbsp;Romain Appay,&nbsp;Solène Evrard,&nbsp;Pascale Varlet,&nbsp;Valérie Rigau,&nbsp;The Biopathology RENOCLIP-LOC network","doi":"10.1111/bpa.13223","DOIUrl":"10.1111/bpa.13223","url":null,"abstract":"<p>We report here about two novel tumours classified as extraventricular neurocytomas (EVN) using DNA-methylation profiling, associated with NTRK2 fusions instead of the usual FGFR1 alterations so far attributed to this tumoural entity. We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Degeneration of olivospinal tract in the upper cervical spinal cord of multiple system atrophy patients: Reappraisal of Helweg's triangular tract","authors":"Takashi Ando,&nbsp;Yuichi Riku,&nbsp;Akio Akagi,&nbsp;Hiroaki Miyahara,&nbsp;Takashi Uematsu,&nbsp;Ikuko Aiba,&nbsp;Jun Sone,&nbsp;Masahisa Katsuno,&nbsp;Mari Yoshida,&nbsp;Yasushi Iwasaki","doi":"10.1111/bpa.13226","DOIUrl":"10.1111/bpa.13226","url":null,"abstract":"<p>Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA. We examined 97 spinal cords from consecutively autopsied patients with MSA. Myelin staining revealed that 22 cords (22.7%) had small, bilateral, triangular-shaped tract degeneration in the boundary of the anterior and lateral funiculi, which appeared continuously from C1 to C5. The anatomical pathway of the degenerated tract was consistent with the description of the olivospinal tract provided by Helweg in 1888. The MSA patients showing degeneration of this tract were younger at disease onset (average: 56.4 ± 8.7 years, range: 42–74), and had longer disease duration (average: 10.1 ± 4.8 years, range: 2–25) and more severe olivopontocerebellar changes compared to other MSA patients. Quantitative analyses revealed that patients with olivospinal tract degeneration had a lower neuronal density in the inferior olivary nucleus compared to other patients. Microglial density in this tract was negatively correlated with the neuronal density in the inferior olivary nucleus. The densities of glial cytoplasmic inclusions in the inferior olivary nucleus and in the olivospinal tract were strongly correlated with each other. Neurologically healthy controls (<i>n</i> = 22) and disease controls with Lewy body disease (<i>n</i> = 30), amyotrophic lateral sclerosis (<i>n</i> = 30), and progressive supranuclear palsy (<i>n</i> = 30) did not present the olivospinal tract degeneration. Our results indicate an impairment of the neural connection between the inferior olivary nucleus and the spinal cord in MSA patients, which may develop in a descending manner.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated analysis of gray matter damage in aged mice reveals impaired remyelination in the cuprizone model","authors":"Stefan Gingele,&nbsp;Thiemo M. Möllenkamp,&nbsp;Florian Henkel,&nbsp;Lara-Jasmin Schröder,&nbsp;Martin W. Hümmert,&nbsp;Thomas Skripuletz,&nbsp;Martin Stangel,&nbsp;Viktoria Gudi","doi":"10.1111/bpa.13218","DOIUrl":"10.1111/bpa.13218","url":null,"abstract":"<p>Multiple sclerosis is a chronic autoimmune disease of the central nervous system characterized by myelin loss, axonal damage, and glial scar formation. Still, the underlying processes remain unclear, as numerous pathways and factors have been found to be involved in the development and progression of the disease. Therefore, it is of great importance to find suitable animal models as well as reliable methods for their precise and reproducible analysis. Here, we describe the impact of demyelination on clinically relevant gray matter regions of the hippocampus and cerebral cortex, using the previously established cuprizone model for aged mice. We could show that bioinformatic image analysis methods are not only suitable for quantification of cell populations, but also for the assessment of de- and remyelination processes, as numerous objective parameters can be considered for reproducible measurements. After cuprizone-induced demyelination, subsequent remyelination proceeded slowly and remained incomplete in all gray matter areas studied. There were regional differences in the number of mature oligodendrocytes during remyelination suggesting region-specific differences in the factors accounting for remyelination failure, as, even in the presence of oligodendrocytes, remyelination in the cortex was found to be impaired. Upon cuprizone administration, synaptic density and dendritic volume in the gray matter of aged mice decreased. The intensity of synaptophysin staining gradually restored during the subsequent remyelination phase, however the expression of MAP2 did not fully recover. Microgliosis persisted in the gray matter of aged animals throughout the remyelination period, whereas extensive astrogliosis was of short duration as compared to white matter structures. In conclusion, we demonstrate that the application of the cuprizone model in aged mice mimics the impaired regeneration ability seen in human pathogenesis more accurately than commonly used protocols with young mice and therefore provides an urgently needed animal model for the investigation of remyelination failure and remyelination-enhancing therapies.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant progressive supranuclear palsy and Lewy body pathology presenting with circumscribed visual memory loss: A clinicopathological case","authors":"Christopher Kobylecki,&nbsp;Jennifer C. Thompson,&nbsp;Andrew C. Robinson,&nbsp;Federico Roncaroli,&nbsp;Julie S. Snowden,&nbsp;David M. Mann","doi":"10.1111/bpa.13219","DOIUrl":"10.1111/bpa.13219","url":null,"abstract":"<p>A 70-year-old man presented to the clinic with impairment of visual memory and marked predominantly right sided mesial temporal lobe atrophy on imaging. He died 6 years following symptom onset and neuropathological examination showed concomitant progressive supranuclear palsy and Lewy body pathology. Although he did not fulfil clinical criteria for either condition at presentation, we propose that interactions between the two pathologies in mesial temporal regions could result in this atypical clinical phenotype.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal Di-methoxyethyl phthalate exposure impairs cortical neurogenesis and synaptic activity in the mice","authors":"Moon Yi Ko,&nbsp;Heejin Park,&nbsp;Sun-Hwa Chon,&nbsp;Byoung-Seok Lee,&nbsp;Sin-Woo Cha,&nbsp;Sung-Ae Hyun,&nbsp;Minhan Ka","doi":"10.1111/bpa.13221","DOIUrl":"10.1111/bpa.13221","url":null,"abstract":"<p>Di-methoxyethyl phthalate (DMEP) is a well-known environmentally prevalent endocrine disruptor and may be associated with neurodevelopmental disorders including attention deficit/hyperactivity disorder and intellectual disability. However, the regulatory mechanisms leading to these neurodevelopmental disorders are still poorly understood. Here, we demonstrate that prenatal DMEP exposure causes abnormal brain morphology and function in the mice. DMEP (50 mg/kg) was chronically administered to pregnant mice orally once a day starting on embryonic day 0 (E0) to breast-feeding cessation for the fetus. We found that prenatal DMEP exposure significantly reduced the number of neurons in the parietal cortex by impairing neurogenesis and gliogenesis during the developing cortex. Moreover, we found that prenatal DMEP exposure impaired dendritic spine architectures and synaptic activity in the parietal cortex. Finally, prenatal DMEP exposure in mice induces hyperactivity and reduces anxiety behaviors. Altogether, our study demonstrates that prenatal DMEP exposure leads to abnormal behaviors via impairment of neurogenesis and synaptic activity.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPI1 activates TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells","authors":"Yifu Song,&nbsp;Yaochuan Zhang,&nbsp;Xiaoliang Wang,&nbsp;Xiaodi Han,&nbsp;Mengwu Shi,&nbsp;Ling Xu,&nbsp;Juanhan Yu,&nbsp;Li Zhang,&nbsp;Sheng Han","doi":"10.1111/bpa.13217","DOIUrl":"10.1111/bpa.13217","url":null,"abstract":"<p>Glioma stem cells (GSCs) exhibit diverse molecular subtypes with the mesenchymal (MES) population representing the most malignant variant. The oncogenic potential of <i>Salmonella</i> pathogenicity island 1 (SPI1), an oncogenic transcription factor, has been established across various human malignancies. In this study, we explored the association between the SPI1 pathway and the MES GSC phenotype. Through comprehensive analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas glioma databases, along with patient-derived GSC cultures, we analyzed SPI1 expression. Using genetic knockdown and overexpression techniques, we assessed the functional impact of SPI1 on GSC MES marker expression, invasion, proliferation, self-renewal, and sensitivity to radiation in vitro, as well as its influence on tumor formation in vivo. Additionally, we investigated the downstream signaling cascades activated by SPI1. Our findings revealed a positive correlation between elevated SPI1 expression and the MES phenotype, which in turn, correlated with poor survival. SPI1 enhanced GSC MES differentiation, self-renewal, and radioresistance in vitro, promoting tumorigenicity in vivo. Mechanistically, SPI1 augmented the transcriptional activity of both TGF-β1 and FKBP12 while activating the non-canonical PI3K/Akt pathway. Notably, inhibition of TGF-β1/PI3K/Akt signaling partially attenuated SPI1-induced GSC MES differentiation and its associated malignant phenotype. Collectively, our results underscore SPI1's role in activating TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12, thereby supporting the aggressive MES phenotype of GSCs. Therefore, SPI1 emerges as a potential therapeutic target in glioma treatment.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Society News","authors":"","doi":"10.1111/bpa.13095","DOIUrl":"https://doi.org/10.1111/bpa.13095","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"33 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50136414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly-GA immunohistochemistry is a reliable tool for detecting C9orf72 hexanucleotide repeat expansions","authors":"Jordan Carroll,&nbsp;Heather McCann,&nbsp;Glenda M. Halliday,&nbsp;John B. Kwok,&nbsp;Carol Dobson-Stone,&nbsp;Claire E. Shepherd","doi":"10.1111/bpa.13216","DOIUrl":"10.1111/bpa.13216","url":null,"abstract":"<p>Poly-GA immunohistochemistry (A) on formalin fixed paraffin embedded cerebellum sections shows a similar distribution to p62 antibody (B) and reliably identifies neuronal cytoplasmic inclusions and neurites in cases with known <i>C9orf72</i> repeat expansion. This is useful in the research setting where genetic testing has not been performed in life or suitable tissue is not avilable post-mortem.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41191949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis","authors":"Fumiaki Mori,&nbsp;Hina Yasui,&nbsp;Yasuo Miki,&nbsp;Tomoya Kon,&nbsp;Akira Arai,&nbsp;Hidekachi Kurotaki,&nbsp;Masahiko Tomiyama,&nbsp;Koichi Wakabayashi","doi":"10.1111/bpa.13215","DOIUrl":"10.1111/bpa.13215","url":null,"abstract":"<p>TDP-43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP-43 in ALS, corresponding to nonfibrillar TDP-43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP-43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP-43 inclusions. Formalin-fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2–5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR-positive. In short-duration and standard-duration ALS, the number of HuR-positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short-duration ALS than in standard-duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome-like granular structures in DPCS areas and RIs were labeled with anti-HuR, whereas skeins were not. These findings suggest that colocalization of TDP-43 and SGs occurs at the early stage of TDP-43 aggregation.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LATE-NC in Alzheimer's disease: Molecular aspects and synergies","authors":"Sandra O. Tomé,&nbsp;Klara Gawor,&nbsp;Dietmar Rudolf Thal","doi":"10.1111/bpa.13213","DOIUrl":"10.1111/bpa.13213","url":null,"abstract":"<p>Alzheimer's disease (AD) is classically characterized by senile plaques and neurofibrillary tangles (NFTs). However, multiple copathologies can be observed in the AD brain and contribute to the development of cognitive decline. Limbic-predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC) accumulates in the majority of AD cases and leads to more severe cognitive decline compared with AD pathology alone. In this review, we focus on the synergistic relationship between LATE-NC and tau in AD, highlighting the aggravating role of TDP-43 aggregates on tau pathogenesis and its impact on the clinical picture and therapeutic strategies. Additionally, we discuss to what extent the molecular patterns of LATE-NC in AD differ from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) neuropathological changes. Thus, we highlight the importance of tau and TDP-43 synergies for subtyping AD patients, which may respond differently to therapeutic interventions depending on the presence of comorbid LATE-NC.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}