Journal of Neuropathology and Experimental Neurology最新文献

Mevalonate kinase deficiency: Neuropathologic findings in an autopsy brain. 甲羟戊酸激酶缺乏：尸检脑的神经病理学发现。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-31 DOI: 10.1093/jnen/nlaf094

Alexander Lokken, Eric Goold, Jessica M Comstock, Changhong Xing

引用次数: 0

An autopsy case of facial-onset sensory and motor neuronopathy with central sleep apnea syndrome. 面部发病的感觉和运动神经病变伴中枢性睡眠呼吸暂停综合征的尸检病例。

IF 3 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-28 DOI: 10.1093/jnen/nlaf050

Asami Munekane, Taiji Nagai, Yuta Fukai, Hirotake Nishimura, Yutaka Ohsawa, Yoshihide Sunada, Masahito Mihara

引用次数: 0

Autophagy impairment is associated with enhanced satellite cell activation in muscle biopsies from younger late-onset Pompe disease patients. 在年轻晚发性庞贝病患者的肌肉活检中，自噬损伤与卫星细胞激活增强相关。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-26 DOI: 10.1093/jnen/nlaf083

Gianmarco Severa, Sultan Bastu, Giovanni Umberto Borin, Xavier Decrouy, Anna Codina, Kaouthar Kefi, Baptiste Periou, Aleksandra Nadaj-Pakleza, Béatrice Lannes, Sabrina Sacconi, Claude-Alain Maurage, Céline Tard, Cristina Jou, Andres Nascimiento Osorio, Valentina Taglietti, Edoardo Malfatti

{"title":"Autophagy impairment is associated with enhanced satellite cell activation in muscle biopsies from younger late-onset Pompe disease patients.","authors":"Gianmarco Severa, Sultan Bastu, Giovanni Umberto Borin, Xavier Decrouy, Anna Codina, Kaouthar Kefi, Baptiste Periou, Aleksandra Nadaj-Pakleza, Béatrice Lannes, Sabrina Sacconi, Claude-Alain Maurage, Céline Tard, Cristina Jou, Andres Nascimiento Osorio, Valentina Taglietti, Edoardo Malfatti","doi":"10.1093/jnen/nlaf083","DOIUrl":"https://doi.org/10.1093/jnen/nlaf083","url":null,"abstract":"Late-onset Pompe disease (LOPD) is caused by α-glucosidase (GAA) deficiency, leading to glycogen accumulation resulting in progressive muscular weakness and respiratory insufficiency. Glycogen overload, vacuolation, and autophagic accumulation are the histological hallmarks of the disease. However, markers capable of tracking the progression of LOPD across different disease stages remain insufficiently characterized. We performed a comprehensive myopathologic analysis of eleven LOPD muscle biopsies from untreated patients (age range 7-69 years) and compared them to eleven biopsies from histologically normal age-matched controls. The cohort was divided into two groups considering the age at muscle biopsy below or above 33 years: (1) younger LOPD and (2) older LOPD, respectively. We quantified periodic acid-Schiff-positive fibers, vacuolated fibers using a novel vacuolation severity score, autophagic markers, and satellite cell behavior. We observed prominent vacuolization, glycogen overload, and autophagic bodies in younger LOPD. Moreover, this group showed higher regenerative features accompanied by an increase in the percentages of active satellite cells compared to older LOPD. In conclusion, autophagy impairment correlates with enhanced satellite cell activation in muscle biopsies from younger LOPD patients. These findings suggest that stimulating satellite cell activity may hold therapeutic potential for addressing LOPD progression in its early stages.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lesion level and severity acutely influence metabolomic profiles in spinal cord injury. 损伤程度和严重程度严重影响脊髓损伤的代谢组学特征。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-26 DOI: 10.1093/jnen/nlaf082

Abi G Yates, Steven Dierksmeier, Yvonne Couch, Timothy D W Claridge, Fay Probert, Daniel C Anthony, Marc J Ruitenberg

{"title":"Lesion level and severity acutely influence metabolomic profiles in spinal cord injury.","authors":"Abi G Yates, Steven Dierksmeier, Yvonne Couch, Timothy D W Claridge, Fay Probert, Daniel C Anthony, Marc J Ruitenberg","doi":"10.1093/jnen/nlaf082","DOIUrl":"https://doi.org/10.1093/jnen/nlaf082","url":null,"abstract":"Changes in the peripheral metabolome, particularly in the blood, may provide biomarkers for assessing lesion severity and predicting outcomes after spinal cord injury (SCI). Using principal component analysis (PCA) and Orthogonal Partial Least Squares Discriminatory Analysis (OPLS-DA), we sought to discover how SCI severity and location acutely affect the nuclear magnetic resonance-acquired metabolome of the blood, spinal cord, and liver at 6 h post-SCI in mice. Unsupervised PCA of the spinal cord metabolome separated mild (30 kdyne) and severe (70 kdyne) contusion injury groups but did not distinguish between lesion level. However, OPLS-DA could discriminate thoracic level T2 from T9 lesions in both blood plasma (accuracy 86 ± 6%) and liver (accuracy 89 ± 5%) samples. These differences were dependent on alterations in energy metabolites (lactate and glucose), lipoproteins, and lipids. Lactate was the most discriminatory between mild and severe injury at T2, whereas overlapping valine/proline resonances were most discriminatory between injury severities at T9. Plasma lactate correlated with blood-spinal cord barrier breakdown and plasma glucose with microglial density. We propose that peripheral biofluid metabolites can serve as biomarkers of SCI severity and associated pathology at the lesion site; their predictive value is most accurate when the injury level is also considered.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knocking down RFWD3 suppresses the growth and migration of glioblastoma cells by blocking G2/M cycle progression. 抑制RFWD3通过阻断G2/M周期进程来抑制胶质母细胞瘤细胞的生长和迁移。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-23 DOI: 10.1093/jnen/nlaf087

Zhongfei Hao, Yaming Han, Yunfei Bo, Liwen Cao, Huijie Fang, Yufei Zhang, Qingbin Li

{"title":"Knocking down RFWD3 suppresses the growth and migration of glioblastoma cells by blocking G2/M cycle progression.","authors":"Zhongfei Hao, Yaming Han, Yunfei Bo, Liwen Cao, Huijie Fang, Yufei Zhang, Qingbin Li","doi":"10.1093/jnen/nlaf087","DOIUrl":"https://doi.org/10.1093/jnen/nlaf087","url":null,"abstract":"Glioblastoma (GBM) is the most common and lethal primary malignant tumor of the adult central nervous system, accounting for approximately half of all gliomas. Although RING finger and WD repeat domain 3 (RFWD3) has been implicated in the regulation of various cancers, its role and underlying mechanisms in GBM progression remain unclear. In this study, analysis of the GEPIA online database confirmed that RFWD3 expression is significantly elevated in GBM tumor tissues. We found increased RFWD3 protein levels in U87 and T98 GBM cell lines and that suppression of RFWD3 markedly reduced cell viability and increased apoptosis in the GBM lines. Moreover, RFWD3 knockdown significantly inhibited their migration and invasion. Flow cytometry analysis revealed that RFWD3 inhibition induced G2/M cell cycle arrest (U87: G1 phase from 69.03% to 50.48%, G2/M phase from 16.54% to 33.01%; T98: G1 phase from 67.31% to 48.32%, G2/M phase from 17.10% to 33.73%). Furthermore, suppression of RFWD3 downregulated the Wnt/β-catenin signaling pathway. These findings indicate that RFWD3 promotes GBM cell growth and migration by facilitating G2/M phase progression through the Wnt/β-catenin pathway. Targeting RFWD3 may represent a promising strategy for inhibiting GBM progression.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sodium butyrate improves the effects of brain injury in a small-for-gestational-age rat model by activating the JAK1/STAT3 pathway. 丁酸钠通过激活JAK1/STAT3通路改善小胎龄大鼠模型脑损伤的影响。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-23 DOI: 10.1093/jnen/nlaf085

Rui Zhang, Xiaona Chen, Qiuyue Shen, Lili Liu, Xinlin Hou, Nana Liu

{"title":"Sodium butyrate improves the effects of brain injury in a small-for-gestational-age rat model by activating the JAK1/STAT3 pathway.","authors":"Rui Zhang, Xiaona Chen, Qiuyue Shen, Lili Liu, Xinlin Hou, Nana Liu","doi":"10.1093/jnen/nlaf085","DOIUrl":"https://doi.org/10.1093/jnen/nlaf085","url":null,"abstract":"The mechanisms of cognitive impairment in small-for-gestational-age (SGA) infants remain unclear. We investigated clinical effects and mechanisms of sodium butyrate (NaB) treatment in a SGA rat model. Behavioral tests, immunohistochemistry, and molecular biology analysis were performed on controls and on SGA rats divided into SGA, SGA + NaB, and SGA + NaB + upadacitinib (a JAK1 inhibitor) groups. Compared to the controls, SGA rats showed weakened neuroreflexes, impaired short-term learning and memory, and manifestations of anxiety and depression. Hippocampal neurons were damaged and apoptotic, and expression of pro-inflammatory factors IL-6 and TNF-α and the JAK1/STAT3 inflammatory pathway were increased in the SGA rats. NaB improved neuroreflexes, learning and memory, anxiety and depressive behaviors, and apoptosis of hippocampal neurons in SGA rats whereas NaB + upadacitinib treatment did not significantly improve these indicators. NaB upregulated JAK1/STAT3 pathway expression in hippocampal neurons of SGA rats and downregulated IL-6 and TNF-α expression; NaB + upadacitinib treatment had the opposite effects. Thus, NaB improved the neurobehavioral performance of SGA rats and reduced damage of hippocampal neurons by activating the JAK1/STAT3 pathway. This study reveals a mechanism of cognitive impairment in SGA infants, providing possible new therapeutic targets.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular amyloidosis in peripheral nerve and skeletal muscle. 周围神经和骨骼肌的细胞内淀粉样变。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-23 DOI: 10.1093/jnen/nlaf088

Grace K Grafham, Gloria Mak, Sandra Grant, Alison Murphy, Steven K Baker, Mark Tarnopolsky, Jian-Qiang Lu

{"title":"Intracellular amyloidosis in peripheral nerve and skeletal muscle.","authors":"Grace K Grafham, Gloria Mak, Sandra Grant, Alison Murphy, Steven K Baker, Mark Tarnopolsky, Jian-Qiang Lu","doi":"10.1093/jnen/nlaf088","DOIUrl":"https://doi.org/10.1093/jnen/nlaf088","url":null,"abstract":"Amyloidosis is an etiologically heterogeneous group of disorders pathologically characterized by the extracellular deposition of amyloid fibrils, leading to tissue damage. It commonly affects the peripheral nervous system and occasionally involves skeletal muscle. The pathogenic mechanisms driving cellular injury in amyloidosis remain elusive. In this study, we examined 3 sural nerve and 5 skeletal muscle biopsies from patients with amyloidosis to localize the deposition of amyloid fibrils. Histologically, the nerve biopsies showed axonal degeneration and Schwann cell (SC) changes; muscle biopsies demonstrated variable myopathic and neurogenic features with multifocal amyloid deposition, including within intramuscular nerves. Electron microscopy identified both intracellular and extracellular amyloid deposition in all 8 biopsies. The ultrastructural localization of amyloid fibrils included the nerve and muscle extracellular matrix, as well as the SC processes, peri-/sub-sarcolemmal region of non-necrotic myofibers, and endoneurial and endomysial/perimysial blood vessel cells. Notably, SC processes, particularly bands of Büngner, formed amyloid-related complex inclusions in all 3 nerve cases. These findings suggest that intracellular amyloid deposition is common in peripheral nerve and skeletal muscle and may play a significant role in cellular injury and degeneration, and ultimately the progression of neuropathy and myopathy.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USP22 promotes neuroblastoma growth, metastasis, and glycolysis via mediating the deubiquitination of PDK1. USP22通过介导PDK1的去泛素化促进神经母细胞瘤的生长、转移和糖酵解。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-22 DOI: 10.1093/jnen/nlaf079

Di Zhang, Ting Gu, Gengfei Cao, Chunwei Hu, Huiting Yang

{"title":"USP22 promotes neuroblastoma growth, metastasis, and glycolysis via mediating the deubiquitination of PDK1.","authors":"Di Zhang, Ting Gu, Gengfei Cao, Chunwei Hu, Huiting Yang","doi":"10.1093/jnen/nlaf079","DOIUrl":"https://doi.org/10.1093/jnen/nlaf079","url":null,"abstract":"Deubiquitinating enzymes are important regulators of cancer progression. We explored the role and regulatory mechanisms of the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) in neuroblastoma (NB). USP22 expression was upregulated in NB patient tissue samples and its expression correlated with their overall survival. Knockdown of USP22 in NB cell lines suppressed cell proliferation, invasion and glycolysis, and enhanced apoptosis. A coimmunoprecipitation assay identified a relationship between USP22 and 3-phosphoinositide-dependent protein kinase 1 (PDK1). USP22 stabilized PDK1 expression via deubiquitination; PDK1 overexpression reversed the effects of USP22 knockdown on the malignant behaviors of NB cells. Dual-luciferase reporter assay and RNA immunoprecipitation were utilized to clarify the relationship between Yin Yang-1 (YY1) and USP22. Yin Yang-1 regulated PDK1 expression via promoting USP22 transcription. USP22 knockdown in a xenograft assay also inhibited tumor growth via regulating PDK1. Taken together, these results indicate that USP22 regulated by YY1 plays a promotional role in NB progression by mediating the deubiquitination of PDK1.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IDH-wildtype astrocytoma with FH mutation, epigenetic similarity to IDH-mutant astrocytoma, and hypermethylation of CDKN2A arising in the brainstem. 伴有FH突变的idh野生型星形细胞瘤，与idh突变型星形细胞瘤的表观遗传相似性，以及脑干中出现的CDKN2A高甲基化。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-22 DOI: 10.1093/jnen/nlaf086

Heather L Smith, Drew J Duckett, Melissa Mejia-Bautista, Anas Alshawa, Pouya Jamshidi, Rudolph J Castellani, Rimas V Lukas, James P Chandler, Lawrence J Jennings, Lucas Santana-Santos, Jared T Ahrendsen

引用次数: 0

Spatially resolved transcriptomics reveals a unique disease signature and potential biomarkers for chronic traumatic encephalopathy. 空间解析转录组学揭示了慢性创伤性脑病的独特疾病特征和潜在生物标志物。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-07-18 DOI: 10.1093/jnen/nlaf078

Catherine M Suter, Jennifer E Cropley, Andrew J Affleck, Maggie Lee, Karina Hammond, Brian Gloss, Michael E Buckland

{"title":"Spatially resolved transcriptomics reveals a unique disease signature and potential biomarkers for chronic traumatic encephalopathy.","authors":"Catherine M Suter, Jennifer E Cropley, Andrew J Affleck, Maggie Lee, Karina Hammond, Brian Gloss, Michael E Buckland","doi":"10.1093/jnen/nlaf078","DOIUrl":"https://doi.org/10.1093/jnen/nlaf078","url":null,"abstract":"Chronic traumatic encephalopathy (CTE) is a poorly understood environmental tauopathy uniquely associated with repetitive head injury. It is clinically ambiguous and at present can only be diagnosed post-mortem. There is a pressing need to understand CTE pathophysiology in order to identify targets for possible intervention and biomarkers for in-life diagnosis. However, molecular characterization of the disease is hampered by the stochastic distribution of CTE lesions. Here, we have taken advantage of Visium spatial transcriptomics to map gene expression in discrete CTE lesions and matched normal tissue from the same individuals. In doing so, we derived a common 21-gene \"signature\" of CTE lesions that highlights astrocytic activation, neuroinflammation, blood-brain barrier function, and extracellular matrix remodeling as key features of CTE lesions. Almost all CTE signature genes were strongly expressed in astrocytes and ontological and protein association analyses implicated extracellular matrix functions as drivers of the disease. These findings provide the first glimpse into the intricate molecular dynamics underlying CTE lesions in situ and present 21 candidate molecules for the development of in-life CTE diagnostics.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0