Neuropathology and Applied Neurobiology最新文献

{"title":"Intelligence quotient-genotype association in dystrophinopathies: A systematic review and meta-analysis.","authors":"Carlos Pascual-Morena,&nbsp;Iván Cavero-Redondo,&nbsp;Irene Sequí-Domínguez,&nbsp;Eva Rodríguez-Gutiérrez,&nbsp;María Eugenia Visier-Alfonso,&nbsp;Vicente Martínez-Vizcaíno","doi":"10.1111/nan.12914","DOIUrl":"https://doi.org/10.1111/nan.12914","url":null,"abstract":"<p><strong>Aims: </strong>Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD.</p><p><strong>Methods: </strong>A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean/mean differences and 95% confidence intervals.</p><p><strong>Results: </strong>Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-/Dp140+/Dp71+, Dp427-/Dp140-/Dp71+ and Dp427-/Dp140-/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-/Dp140-/Dp71+ vs Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71- vs Dp427-/Dp140-/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively.</p><p><strong>Conclusions: </strong>The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12914"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073777","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":"Timing is everything: A connection between medulloblastoma prognosis and foetal cerebellar development.","authors":"Daniel Williamson, Edward C Schwalbe, Simon Bailey, Steven C Clifford","doi":"10.1111/nan.12903","DOIUrl":"10.1111/nan.12903","url":null,"abstract":"<p><p>The childhood brain tumour medulloblastoma is typically classified into multiple discrete molecular subgroups with characteristic DNA methylation and expression patterns. Several of these subgroups are used as, or proposed to be, an effective basis for treatment stratification. Here, we highlight the close connection between the findings described in a recent series of studies which, together, strongly imply a continuous association between survival outcome, the transcriptional profile of a Group3/Group4 (i.e. non-WNT/non-SHH) medulloblastoma and the specific point during early foetal cerebellar development at which initial pathogenic disruption took place. This has important implications for future efforts to model the disease by incorporating driving molecular features into their specific developmental context. This further suggests that instead of relying upon discrete DNA methylation subgroups, using expression biomarkers as the basis of a continuous risk predictor may produce a more effective risk stratification of patients with Group3/Group4 medulloblastoma.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12903"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073221","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":"Erratum.","authors":"","doi":"10.1111/nan.12906","DOIUrl":"https://doi.org/10.1111/nan.12906","url":null,"abstract":"FIGURE 5. Axonal (Wallerian) degeneration in adult human sural nerve. (Wallerian) degeneration in adult human sural nerve. Loss of neurofilament staining of larger axons is apparent within areas of myelin basic protein (MBP)-stained myelin. (A) Toluidine blue-stained plastic sections show myelin ovoids and irregularly shaped myelin sheaths. Scattered Schwann cells associated with myelin and other endoneurial cells contain lipid debris or droplets. Bar = 10 μM. (B) Neurofilament-stained frozen sections show round pale regions (arrow at the top right of image) that likely represent the loss of larger axons within areas of residual myelin. Smaller axons are relatively preserved. Bar = 20 μM. (C) Ultrastructural analysis shows a damaged axon (left) with irregular cytoplasm inside thick myelin associated with surrounding Schwann cell cytoplasm containing myelin debris and lipid droplets (arrow left). An endoneurial macrophage (right) (not likely a Schwann cell as it has no surrounding basal lamina) contains myelin debris and lipid droplets (arrow right). Bars = 2 μM. (D) Acid phosphatase (AcP) stains scattered endoneurial histiocytes (red). Bar = 50 μM. (E) Neural cell adhesion molecule (NCAM) (green) stains non-myelinating Schwann cells (see I). P0 protein (P0) (red) stains myelin sheaths (see H). There is minimal overlap (yellow). (F) NCAM and MBP show overlap (yellow) on both NCAM cells and some MBP-containing myelin. (G) Many MBP myelin regions have central regions with no neurofilament-stained axons (arrow). (H) Scattered P0 regions have central regions with no neurofilament-stained axons (arrow). (I) Most NCAM (red) regions have associated co-stained axons (yellow) suggesting acute axon loss is less prominent among small-sized axons. Bars for E–I = 100 μM. DOI: 10.1111/nan.12906","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12906"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690748","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":"Tuberous sclerosis complex-1 (TSC1) contributes to selective neuronal vulnerability in Alzheimer's disease.","authors":"Bryan A Adriaanse,&nbsp;Sinead Brady,&nbsp;Minghui Wang,&nbsp;Daniel J Beard,&nbsp;Jonathan I Spencer,&nbsp;Jonathan Pansieri,&nbsp;Brad A Sutherland,&nbsp;Margaret M Esiri,&nbsp;Alastair M Buchan,&nbsp;Zameel Cader,&nbsp;Bin Zhang,&nbsp;Gabriele C DeLuca","doi":"10.1111/nan.12904","DOIUrl":"https://doi.org/10.1111/nan.12904","url":null,"abstract":"<p><strong>Aims: </strong>Selective neuronal vulnerability of hippocampal Cornu Ammonis (CA)-1 neurons is a pathological hallmark of Alzheimer's disease (AD) with an unknown underlying mechanism. We interrogated the expression of tuberous sclerosis complex-1 (TSC1; hamartin) and mTOR-related proteins in hippocampal CA1 and CA3 subfields.</p><p><strong>Methods: </strong>A human post-mortem cohort of mild (n = 7) and severe (n = 10) AD and non-neurological controls (n = 9) was used for quantitative and semi-quantitative analyses. We also developed an in vitro TSC1 knockdown model in rat hippocampal neurons, and transcriptomic analyses of TSC1 knockdown neuronal cultures were performed.</p><p><strong>Results: </strong>We found a selective increase of TSC1 cytoplasmic inclusions in human AD CA1 neurons with hyperactivation of one of TSC1's downstream targets, the mammalian target of rapamycin complex-1 (mTORC1), suggesting that TSC1 is no longer active in AD. TSC1 knockdown experiments showed accelerated cell death independent of amyloid-beta toxicity. Transcriptomic analyses of TSC1 knockdown neuronal cultures revealed signatures that were significantly enriched for AD-related pathways.</p><p><strong>Conclusions: </strong>Our combined data point to TSC1 dysregulation as a key driver of selective neuronal vulnerability in the AD hippocampus. Future work aimed at identifying targets amenable to therapeutic manipulation is urgently needed to halt selective neurodegeneration, and by extension, debilitating cognitive impairment characteristic of AD.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12904"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10073220","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":"Corrigendum.","authors":"","doi":"10.1111/nan.12905","DOIUrl":"https://doi.org/10.1111/nan.12905","url":null,"abstract":"The authors regret that in Bergh et al., the funding information for Åsa Petersén was incomplete. The complete funding information is provided below: This work was supported by research grants to RYC and ÅP from the Swedish Research Council (grant numbers 2013/03537 and 2018/02559), ALF grant from Region Skåne, the Royal Physiographic Society of Lund (grant numbers 2016-37869, 2018-39651 and 2019-40523), the Swedish Brain Foundation (grant numbers FO2016-0121 and FO2018-0080), the Åhlén Foundation (grant number mA28/ h17), the Fredrik and Ingrid Thurings Foundation (grant number 2017-00316) and NEURO Sweden (2017 and 2019). RYC was supported by a Swedish Society for Medical Research (SSMF) Postdoctoral Fellowship (grant number P15-0017). ÅP was supported by a research grant from Knut and Alice Wallenberg Foundation (grant number 2019.0467). The authors apologise for any inconvenience this may have caused.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12905"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683823","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":"Increased number and domain of interlaminar astrocytes in layer I of the temporal cortex in epilepsy.","authors":"Nan Zhou,&nbsp;Zhen Fan,&nbsp;Yusheng Tong,&nbsp;Xing Xiao,&nbsp;Yongsheng Xie,&nbsp;Zengxin Qi,&nbsp;Liang Chen","doi":"10.1111/nan.12913","DOIUrl":"https://doi.org/10.1111/nan.12913","url":null,"abstract":"<p><strong>Aim: </strong>The functions of the interlaminar astrocytes in layer I of the human cortex are currently unknown. Here, we aimed to explore whether there is any morphological remodelling of interlaminar astrocytes in layer I of the temporal cortex in epilepsy.</p><p><strong>Methods: </strong>Tissues were obtained from 17 epilepsy surgery patients and 17 post-mortem age-matched controls. In addition, 10 Alzheimer's disease (AD) patients and 10 age-matched controls were used as the disease control group. Paraffin sections (6 μm) and frozen sections (35 or 150 μm) of inferior temporal gyrus tissue were used for immunohistochemistry. With the use of tissue transparency, 3D reconstruction and hierarchical clustering, we performed a quantitative morphological analysis of astrocytes.</p><p><strong>Results: </strong>Upper and lower zones were identified in layer I of the human cortex. Compared with the astrocytes in layers IV-V, layer I interlaminar astrocytes occupied a significantly smaller volume and exhibited shorter and fewer process intersections. Increased Chaslin's gliosis (consisting of types I and II subpial interlaminar astrocytes) and number of glial fibrillary acidic protein (GFAP)-immunoreactive interlaminar astrocytes in layer I of the temporal cortex were confirmed in patients with epilepsy. There was no difference in the number of interlaminar astrocytes in layer I between AD and age-matched control groups. Using tissue transparency and 3D reconstruction technology, the astrocyte domain in the human temporal cortex was classified into four clusters, among which the interlaminar astrocytes in cluster II were more abundant in epilepsy, showing specific topological structures in patients with epilepsy. Furthermore, there was a significant increase in the astrocyte domain of interlaminar cells in layer I of the temporal cortex in patients with epilepsy.</p><p><strong>Conclusion: </strong>The observed significant astrocytic structural remodelling in the temporal cortex of epilepsy patients showed that the astrocyte domain in layer I may play an important role in temporal lobe epilepsy.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 3","pages":"e12913"},"PeriodicalIF":5.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9695353","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":"Motor neuron involvement threatens survival in spinocerebellar ataxia type 1.","authors":"Giulia Coarelli,&nbsp;Maya Tchikviladzé,&nbsp;Pauline Dodet,&nbsp;Isabelle Arnulf,&nbsp;Perrine Charles,&nbsp;Frederic Tankeré,&nbsp;Thomas Similowski,&nbsp;Danielle Seilhean,&nbsp;Alexis Brice,&nbsp;Charles Duyckaerts,&nbsp;Alexandra Durr","doi":"10.1111/nan.12897","DOIUrl":"https://doi.org/10.1111/nan.12897","url":null,"abstract":"Sorbonne Université, Paris Brain Institute (ICM Institut du Cerveau), INSERM, CNRS, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France Department of Genetics, Pitié-Salpêtrière Charles-Foix University Hospital, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, 75013, France Sleep Disorders Unit, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France; ICM, Sorbonne Université, Inserm U 1127, CNRS UMR, Paris, 7225, France Department of Otolaryngology-Head and Neck Surgery, Pitié-Salpêtrière Charles-Foix University Hospital, Assistance Publique – Hôpitaux de Paris (AP-HP), Sorbonne Université, Paris, 75013, France Département R3S (Respiration, Réanimation, Réhabilitation respiratoire, Sommeil), Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique; AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Paris, F-75013, France Laboratoire de Neuropathologie R. Escourolle, Pitié-Salpêtrière Charles-Foix University Hospital, Assistance Publique – Hôpitaux de Paris (AP-HP), Sorbonne Université, Paris, 75013, France","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12897"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9366537","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":"Muscleblind-like 2 knockout shifts adducin 1 isoform expression and alters dendritic spine dynamics of cortical neurons during brain development.","authors":"Chia-Wei Huang,&nbsp;Kuang-Yung Lee,&nbsp;Peng-Tzu Lin,&nbsp;Fang-Shin Nian,&nbsp;Haw-Yuan Cheng,&nbsp;Chien-Hui Chang,&nbsp;Cheng-Yen Liao,&nbsp;Yen-Lin Su,&nbsp;Carol Seah,&nbsp;Ching Li,&nbsp;Yu-Fu Chen,&nbsp;Mei-Hsuan Lee,&nbsp;Jin-Wu Tsai","doi":"10.1111/nan.12890","DOIUrl":"https://doi.org/10.1111/nan.12890","url":null,"abstract":"Muscleblind‐like 2 (MBNL2) plays a crucial role in regulating alternative splicing during development and mouse loss of MBNL2 recapitulates brain phenotypes in myotonic dystrophy (DM). However, the mechanisms underlying DM neuropathogenesis during brain development remain unclear. In this study, we aim to investigate the impact of MBNL2 elimination on neuronal development by Mbnl2 conditional knockout (CKO) mouse models.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12890"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423814","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":"Soluble amyloid-β dimers are resistant to amyloid-β prion conversion in vivo suggesting antiprion properties.","authors":"Else F van Gerresheim,&nbsp;Andreas Müller-Schiffmann,&nbsp;Sandra Schäble,&nbsp;Bastijn Koopmans,&nbsp;Maarten Loos,&nbsp;Carsten Korth","doi":"10.1111/nan.12895","DOIUrl":"https://doi.org/10.1111/nan.12895","url":null,"abstract":"According to the instructions for authors, short communications should be published without abstract.","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12895"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9721544","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":"TDP-43 pathology and functional deficits in wild-type and ALS/FTD mutant cyclin F mouse models.","authors":"Annika van Hummel, Miheer Sabale, Magdalena Przybyla, Julia van der Hoven, Gabriella Chan, Astrid F Feiten, Roger S Chung, Lars M Ittner, Yazi D Ke","doi":"10.1111/nan.12902","DOIUrl":"10.1111/nan.12902","url":null,"abstract":"<p><strong>Aims: </strong>Amyotrophic lateral sclerosis (ALS) is characterised by a progressive loss of upper and lower motor neurons leading to muscle weakness and eventually death. Frontotemporal dementia (FTD) presents clinically with significant behavioural decline. Approximately 10% of cases have a known family history, and disease-linked mutations in multiple genes have been identified in FTD and ALS. More recently, ALS and FTD-linked variants have been identified in the CCNF gene, which accounts for an estimated 0.6% to over 3% of familial ALS cases.</p><p><strong>Methods: </strong>In this study, we developed the first mouse models expressing either wild-type (WT) human CCNF or its mutant pathogenic variant S621G to recapitulate key clinical and neuropathological features of ALS and FTD linked to CCNF disease variants. We expressed human CCNF WT or CCNF^S621G throughout the murine brain by intracranial delivery of adeno-associated virus (AAV) to achieve widespread delivery via somatic brain transgenesis.</p><p><strong>Results: </strong>These mice developed behavioural abnormalities, similar to the clinical symptoms of FTD patients, as early as 3 months of age, including hyperactivity and disinhibition, which progressively deteriorated to include memory deficits by 8 months of age. Brains of mutant CCNF_S621G mice displayed an accumulation of ubiquitinated proteins with elevated levels of phosphorylated TDP-43 present in both CCNF_WT and mutant CCNF_S621G mice. We also investigated the effects of CCNF expression on interaction targets of CCNF and found elevated levels of insoluble splicing factor proline and glutamine-rich (SFPQ). Furthermore, cytoplasmic TDP-43 inclusions were found in both CCNF_WT and mutant CCNF_S621G mice, recapitulating the key hallmark of FTD/ALS pathology.</p><p><strong>Conclusions: </strong>In summary, CCNF expression in mice reproduces clinical presentations of ALS, including functional deficits and TDP-43 neuropathology with altered CCNF-mediated pathways contributing to the pathology observed.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 2","pages":"e12902"},"PeriodicalIF":5.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360740","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}