Neuropathology and Applied Neurobiology最新文献

{"title":"A centronuclear myopathy-causing mutation in dynamin-2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease.","authors":"Jorge Arriagada-Diaz,&nbsp;Carolina Flores-Muñoz,&nbsp;Bárbara Gómez-Soto,&nbsp;Marjorie Labraña-Allende,&nbsp;Michelle Mattar-Araos,&nbsp;Lorena Prado-Vega,&nbsp;Fernando Hinostroza,&nbsp;Ivana Gajardo,&nbsp;María José Guerra-Fernández,&nbsp;Jorge A Bevilacqua,&nbsp;Ana M Cárdenas,&nbsp;Marc Bitoun,&nbsp;Alvaro O Ardiles,&nbsp;Arlek M Gonzalez-Jamett","doi":"10.1111/nan.12918","DOIUrl":"https://doi.org/10.1111/nan.12918","url":null,"abstract":"<p><strong>Aims: </strong>Dynamin-2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2-linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin-2 CNM-causing mutation influences the CNS function.</p><p><strong>Methods: </strong>Heterozygous mice harbouring the p.R465W mutation in the dynamin-2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests.</p><p><strong>Results: </strong>HTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin-2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition.</p><p><strong>Conclusion: </strong>Our findings suggest that the dynamin-2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 4","pages":"e12918"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512554","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":"Adult-onset Alexander disease with unusual inflammatory features and a novel GFAP mutation in two patients.","authors":"Fouzia Ziad,&nbsp;Gert Cypers,&nbsp;Matthew Phillips,&nbsp;Piet Vanhoenacker,&nbsp;Arne Hostens,&nbsp;Satish Yadavraj,&nbsp;Duncan Lamont,&nbsp;Thomas Robertson","doi":"10.1111/nan.12927","DOIUrl":"https://doi.org/10.1111/nan.12927","url":null,"abstract":"central respiratory failure. Histopathological examination of the lesion in the medulla oblongata showed","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 4","pages":"e12927"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512594","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":"Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers high-grade gliomas.","authors":"David E Reuss,&nbsp;Susanna M Downing,&nbsp;Cristel V Camacho,&nbsp;Yong-Dong Wang,&nbsp;Rosario M Piro,&nbsp;Christel Herold-Mende,&nbsp;Zhao-Qi Wang,&nbsp;Thomas G Hofmann,&nbsp;Felix Sahm,&nbsp;Andreas von Deimling,&nbsp;Peter J McKinnon,&nbsp;Pierre-Olivier Frappart","doi":"10.1111/nan.12915","DOIUrl":"https://doi.org/10.1111/nan.12915","url":null,"abstract":"<p><strong>Aims: </strong>Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder caused by hypomorphic mutations of NBS1. NBS1 is a member of the MRE11-RAD50-NBS1 (MRN) complex that binds to DNA double-strand breaks and activates the DNA damage response (DDR). Nbs1 inactivation in neural progenitor cells leads to microcephaly and premature death. Interestingly, p53 homozygous deletion rescues the NBS1-deficient phenotype allowing long-term survival. The objective of this work was to determine whether simultaneous inactivation of Nbs1 and p53 in neural progenitors triggered brain tumorigenesis and if so in which category this tumour could be classified.</p><p><strong>Methods: </strong>We generated a mouse model with simultaneous genetic inactivation of Nbs1 and p53 in embryonic neural stem cells and analysed the arising tumours with in-depth molecular analyses including immunohistochemistry, array comparative genomic hybridisation (aCGH), whole exome-sequencing and RNA-sequencing.</p><p><strong>Results: </strong>NBS1/P53-deficient mice develop high-grade gliomas (HGG) arising in the olfactory bulbs and in the cortex along the rostral migratory stream. In-depth molecular analyses using immunohistochemistry, aCGH, whole exome-sequencing and RNA-sequencing revealed striking similarities to paediatric human HGG with shared features with radiation-induced gliomas (RIGs).</p><p><strong>Conclusions: </strong>Our findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 4","pages":"e12915"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136845","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":"Methyl donor supplementation reduces phospho-Tau, Fyn and demethylated protein phosphatase 2A levels and mitigates learning and motor deficits in a mouse model of tauopathy.","authors":"Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D Ke, Lars M Ittner, Estelle Sontag","doi":"10.1111/nan.12931","DOIUrl":"10.1111/nan.12931","url":null,"abstract":"<p><strong>Background: </strong>Reduced folate status and elevated levels of circulating homocysteine are modifiable risk factors for cognitive decline and dementia. Disturbances in one-carbon metabolism are associated with the pathological accumulation of phosphorylated tau, a hallmark feature of prevalent dementia, including Alzheimer's disease and subgroups of frontotemporal dementia.</p><p><strong>Methods: </strong>Here, using transgenic TAU58/2 mouse models of human tauopathy, we tested whether dietary supplementation with L-methylfolate (the active folate form), choline and betaine can reduce tau phosphorylation and associated behavioural phenotypes.</p><p><strong>Results: </strong>TAU58/2 mice fed with the methyl donor-enriched diet showed reduced phosphorylation of tau at the pathological S202 (CP13) and S396/S404 (PHF-1) epitopes and alleviation of associated motor and learning deficits. Compared with mice on the control diet, the decrease in cortical phosphorylated tau levels in mice fed with the methyl donor-enriched diet was associated with enhanced methylation of protein phosphatase 2A, the major brain tau Ser/Thr phosphatase. It also correlated with a reduction in protein levels of Fyn, a tau tyrosine kinase that plays a central role in mediating pathological tau-induced neurodegeneration. Conversely, Fyn expression levels were increased in mice with deficiencies in folate metabolism.</p><p><strong>Conclusions: </strong>Our findings provide the first experimental evidence that boosting one-carbon metabolism with L-methylfolate, choline and betaine can mitigate key pathological, learning and motor deficits in a tauopathy mouse model. They give support to using a combination of methyl donors as a preventive or disease-modifying strategy for tauopathies.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"49 4","pages":"e12931"},"PeriodicalIF":5.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137372","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":"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}