Neurobiology of Disease最新文献

{"title":"Expression of concern: \"Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury\" [NEUROBIOL DIS, Volume 51 (2013) Pages 133-143].","authors":"","doi":"10.1016/j.nbd.2025.106949","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.106949","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"212 ","pages":"106949"},"PeriodicalIF":5.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302572","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":"Expression of concern: \"Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats\" [NEUROBIOL DIS, Volume 95 (2016) Pages 111-121].","authors":"","doi":"10.1016/j.nbd.2025.106948","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.106948","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"212 ","pages":"106948"},"PeriodicalIF":5.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302573","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":"Sphingomyelin-induced glucocorticoid receptor alterations lead to impaired presynaptic plasticity in acid sphingomyelinase deficient neurons","authors":"Sara Naya-Forcano ,&nbsp;Ángel Gaudioso ,&nbsp;Beatriz Soto-Huelin ,&nbsp;Celia García-Vilela ,&nbsp;César Venero ,&nbsp;Edward H. Schuchman ,&nbsp;José A. Esteban ,&nbsp;María Dolores Ledesma","doi":"10.1016/j.nbd.2025.107016","DOIUrl":"10.1016/j.nbd.2025.107016","url":null,"abstract":"<div><div>Acid sphingomyelinase deficiency (ASMD) is a rare disease caused by mutations in the gene encoding ASM, an enzyme that degrades sphingomyelin (SM). In addition to SM accumulation, neuroinflammation and cognitive impairment are pathological hallmarks of neurovisceral ASMD. Since the glucocorticoid system may influence these features, we have characterized it in ASM knockout (ASMko) mice that mimic this form of the disease. While plasma corticosterone levels are not altered in these mice, brain levels of the α, but not the β, isoform of glucocorticoid receptors (GR) are reduced. The reduction is evident in neurons and is due to the accumulation of SM. As a consequence, the expression of the protein, synapsin I, is low in ASMko neurons, leading to the disorganization of synaptic vesicles and to impaired presynaptic plasticity. Treatment with the glucocorticoid hydrocortisone diminished SM levels, increased synapsin I expression, and improved presynaptic function in neuronal cultures and hippocampal slices of ASMko mice. These findings establish, for the first time, a link between the glucocorticoid system and brain pathology in ASMD, highlighting the GR as a potential therapeutic target for this devastating disease.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107016"},"PeriodicalIF":5.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535385","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":"Age-related cerebral amyloid angiopathy accumulation in the APPSw mouse model is associated with perivascular inflammation and brain-wide vascular and inflammatory gene and protein changes","authors":"Katelynn E. Krick ,&nbsp;Erica M. Weekman ,&nbsp;Sherika N. Johnson ,&nbsp;Tiffany L. Sudduth ,&nbsp;Colin B. Rogers ,&nbsp;Emma J. Nicolayson ,&nbsp;Maureen T. Kleinhenz ,&nbsp;Donna M. Wilcock","doi":"10.1016/j.nbd.2025.107013","DOIUrl":"10.1016/j.nbd.2025.107013","url":null,"abstract":"<div><div>Cerebral amyloid angiopathy (CAA) is an extremely common pathology of Alzheimer's disease (AD) included under vascular contributions to cognitive impairment and dementia (VCID). CAA has been reported in 78–98 % of AD cases and has clinical significance when considering side effects that arise when using amyloid targeting immunotherapies. Despite its prevalence, studies addressing CAA mechanisms have been scarce and there are clear gaps in our understanding of how CAA progresses. This study uses Tg2576 mice, who develop CAA over time, to establish a time course of CAA progression at 8-, 14-, and 20-months of age. We identify changes in transcriptomic signatures of glial cells using NanoString nCounter and targeted protein changes using NanoString Digital Spatial Profiling. Meso Scale Discovery and immunohistochemistry are used to establish disease progression. In this study, we saw many changes primarily associated with inflammatory response, with some changes being transient (<em>Tnf, Lsr;</em> VEGF<em>)</em> and others remaining chronically altered (<em>Osmr, Ccl3;</em> CTSD). Overarchingly, many of these changes relate to the perpetuation of inflammation or recruiting additional immune support, which we see across our timepoints. Further, we identified differences in abundance of proteins (CD45, GFAP, CD31) based on presence of CAA positive vessels within a brain region. We also identified sex-specific differences in CAA burden, as well as how glial reactivity and vessel density change during disease progression. This data represents a comprehensive analysis of CAA progression and differential responses to parenchymal and vascular amyloid that could inform future basic and clinical studies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107013"},"PeriodicalIF":5.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535386","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":"The P2X7 receptor in depression: Novel insights and therapeutic implications","authors":"Yue-ting Zhong ,&nbsp;Chao Pi ,&nbsp;Ying Zuo ,&nbsp;Yan Wei ,&nbsp;Wen Li ,&nbsp;Yong-qiang Jiang ,&nbsp;Lei Tao ,&nbsp;Wen-wu Zheng ,&nbsp;Jun Jiang ,&nbsp;Yan Yang ,&nbsp;Shi-feng Chu ,&nbsp;Bin-yan Liu ,&nbsp;Ke-zhi Liu ,&nbsp;Yu-meng Wei ,&nbsp;Ling Zhao","doi":"10.1016/j.nbd.2025.107011","DOIUrl":"10.1016/j.nbd.2025.107011","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a heterogeneous mental disorder involving multiple pathogenic mechanisms. Current first-line antidepressant medications suffer from slow onset of action, limited effectiveness, and high side effects, necessitating the search for new therapeutic targets. Targeting cytokines or receptors is increasingly recognized in innovative depression treatment protocols. The P2X7 receptor (P2X7R) plays a key role in central nervous system signaling and is considered a potential therapeutic target for depression. Recent studies have focused on the fact that P2X7R modulates inflammatory and immune responses, which may contribute to the development of depression. However, the full extent of P2X7R's involvement in depression remains unclear. This review provides a comprehensive overview of the discovery, structure, and properties of P2X7R. We delve into the role of P2X7R in the pathogenesis of depression, focusing on neuroinflammation, oxidative stress, mitochondrial dysfunction, and reduced synaptic plasticity. Additionally, we discuss the clinical applications of P2X7R antagonists. By highlighting the significant role and therapeutic potential of the P2X7 receptor as a pharmacological target for depression, this review aims to provide new research perspectives and theoretical basis for the development of antidepressant drugs.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107011"},"PeriodicalIF":5.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518130","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":"Klinefelter syndrome: A neurodevelopmental disease of the synapse","authors":"Helen Zhao ,&nbsp;Dan Zhou ,&nbsp;Yolanda Feng ,&nbsp;Gabriel G. Haddad","doi":"10.1016/j.nbd.2025.107010","DOIUrl":"10.1016/j.nbd.2025.107010","url":null,"abstract":"<div><div><em>Klinefelter syndrome (KS; 47,XXY)</em> is the most common sex chromosome disorder, affecting approximately 1 in every 500 to 650 newborn males. Children with KS display a spectrum of phenotypic manifestations, including abnormal neurocognitive phenotypes. However, due to the limited research focusing on the central nervous system, our understanding of the neurobiology of KS at the cellular and molecular levels remains largely unclear. In this study, we utilized cortical organoids derived from pluripotent stem cells and transcriptomic analysis to explore the mechanisms underlying early brain developmental defects in KS patients. We demonstrate that KS organoids display altered neurogenesis, gliogenesis, and glutamate signaling pathways. We believe these early alterations contribute to the abnormal brain development and later cognitive phenotypes in KS patients.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107010"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512183","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":"Interneuron transcriptomics reveals pathologic markers of Alzheimer's disease progression","authors":"Kevin S. Chen ,&nbsp;Mohamed H. Noureldein ,&nbsp;Diana M. Rigan ,&nbsp;John M. Hayes ,&nbsp;Kyle J. Loi ,&nbsp;Junguk Hur ,&nbsp;Masha G. Savelieff ,&nbsp;Eva L. Feldman","doi":"10.1016/j.nbd.2025.107012","DOIUrl":"10.1016/j.nbd.2025.107012","url":null,"abstract":"<div><div>Alzheimer's disease (AD) exhibits imbalance between neuronal excitation and inhibition, likely secondary to interneuron dysfunction. To reveal underlying mediators, we spatially profiled the transcriptome of neuronal subtypes in 5XFAD versus control mice at early- and late-stage disease. Pooled analysis of neuron types showed expected pathways at early-stage (RNA and protein processing pathways) versus late-stage (neurodegenerative pathways) disease. Early-stage interneurons exhibited alterations in AD-related RNA and protein pathways along with canonical neurodegenerative pathways. Early-stage excitatory neurons, however, showed changes in axon guidance and synapse pathways, without representation of neurodegenerative pathways. Classical neurodegenerative pathways were represented only in late-stage excitatory neurons. Late-stage interneurons instead featured neuronal and synapse pathways along with cellular, cancer, and infection pathways. Our results suggest earlier neurodegenerative pathway involvement in interneurons, represented in excitatory neurons only at later stages, possibly indicating earlier inhibitory neuron involvement. These transcriptomic profiles offer insight into potential AD pathophysiology and therapeutic targets.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107012"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512182","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":"Unconsciousness reshapes the oscillatory topography of the subthalamic nucleus: A comparative study","authors":"Laura Dubach ,&nbsp;Alberto Averna ,&nbsp;Laura Alva ,&nbsp;Ines Debove ,&nbsp;Elena Bernasconi ,&nbsp;Mario Sousa ,&nbsp;Katrin Petermann ,&nbsp;Martin Lenard Lachenmayer ,&nbsp;Paul Krack ,&nbsp;Andreas Nowacki ,&nbsp;Claudio Pollo ,&nbsp;Vladimir Krejci ,&nbsp;Gerd Tinkhauser","doi":"10.1016/j.nbd.2025.107009","DOIUrl":"10.1016/j.nbd.2025.107009","url":null,"abstract":"<div><h3>Background</h3><div>Many centers perform Deep Brain Stimulation (DBS) surgery under general anesthesia (GA), known as asleep DBS. Local field potential (LFP) of the Subthalamic Nucleus (STN) recorded in awake Parkinson's disease (PD) patients revealed important insights into disease mechanism and DBS optimization-strategies. In contrast, the spectral characteristics of oscillations recorded in the GA-induced unconscious state remain only partially understood.</div></div><div><h3>Objectives</h3><div>To contrast the spectral and topographical characteristics of STN-LFPs recorded in both awake and asleep states and assess the clinical DBS response prediction based on neurophysiological hotspot positions.</div></div><div><h3>Methods</h3><div>STN-LFPs were recorded intraoperatively from 69 PD patients (128 hemispheres) awake and 26 patients (51 hemispheres) under propofol-anesthesia using multi-contact DBS electrodes. Spectral power (4 to 400 Hz), topographical hotspot distributions and their clinical predictive values were compared. The relationship between LFPs and frontal-EEG, anesthetic depth and dopamine withdrawal were also evaluated.</div></div><div><h3>Results</h3><div>Asleep LFPs showed increased alpha (8-12 Hz), low-beta (13-20 Hz), and fast-gamma (110-140 Hz) activity, and decreased theta (4-7 Hz), high-beta (21–30 Hz), and low-gamma (35-45 Hz) power, while high-gamma (60-90 Hz), slow-HFO (205-295 Hz) and fast-HFO (305-495 Hz) activity remained unchanged compared to the awake state. Under asleep DBS the spectral topographical map shifted medially, posteriorly and inferiorly, hereby losing its clinical predictive value. STN-LFPs echo propofol-induced changes in frontal-EEG, while time of dopamine withdrawal did not impact asleep-LFP.</div></div><div><h3>Conclusions</h3><div>Unconsciousness reshapes the spectral and spatial topography of the STN in PD patients, hereby losing its predictive values for motor DBS-response. Dynamical changes of spectral features in space may inform future sleep-tailored DBS.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107009"},"PeriodicalIF":5.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369093","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":"Hypo-connected pattern in Parkinson's disease with pure apathy: A dynamic functional connectivity perspective","authors":"Yan Zhi ,&nbsp;Kaidong Chen ,&nbsp;Yiping You ,&nbsp;Yi Ji ,&nbsp;Weiguo Cheng ,&nbsp;Wei Ji ,&nbsp;Guofeng Shi ,&nbsp;Xiangming Fang ,&nbsp;Feng Wang ,&nbsp;Kefei Chen ,&nbsp;Li Zhang","doi":"10.1016/j.nbd.2025.107008","DOIUrl":"10.1016/j.nbd.2025.107008","url":null,"abstract":"<div><h3>Background</h3><div>Apathy, a decline in goal-directed motivated behavior, is a common non-motor symptom in Parkinson's disease (PD). The dynamic information interaction between multiple brain functional networks, crucial for goal-directed behavior, remains unknown in patients with PD and pure apathy (PD-PA). This study thus used the dynamic functional network connectivity (dFNC) analysis to explore the dynamic brain networks changes of apathy in PD.</div></div><div><h3>Methods</h3><div>Thirty patients with PD-PA, 37 patients with PD but not pure apathy (PD-NPA), and 37 healthy controls (HCs) were studied using dFNC analysis to explore dynamic functional connectivity (FC) patterns of brain networks in PD-PA.</div></div><div><h3>Results</h3><div>Seven brain networks were finally identified and configured into four states. Patients with PD-PA showed longer mean dwell time in State 1 when compared to patients with PD-NPA. Furthermore, the mean dwell time of State 1 positively correlated with apathy severity in patients with PD-PA. Generally, State 1 is hypo-connected than other states. In State 1, intra-network FC within the default mode network (DMN) in patients with PD-PA was decreased compared to patients with PD-NPA. Specifically, the FC of the left precuneus and the left medial superior frontal gyrus (SFGmed) within the DMN was decreased.</div></div><div><h3>Conclusions</h3><div>Apathy in PD may be related with prolonged low connectivity in brain networks, particularly the disconnection between the precuneus and SFGmed within the DMN, highlighting impaired information transmission within and between networks as a key mechanism of apathy in PD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107008"},"PeriodicalIF":5.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340276","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":"Targeted neuromodulation of spinal interneurons enhances breathing in chronic spinal cord injury","authors":"Allison Brezinski ,&nbsp;Nicholas Popp ,&nbsp;Katherine Konkel ,&nbsp;Shekar Kurpad ,&nbsp;Kajana Satkunendrarajah","doi":"10.1016/j.nbd.2025.107007","DOIUrl":"10.1016/j.nbd.2025.107007","url":null,"abstract":"<div><div>Respiratory dysfunction is a debilitating consequence of cervical spinal cord injury (cSCI) with few available treatment options. Restoring function in the chronic phase is challenging due to the limited regenerative capacity of the adult central nervous system. This study investigates the targeted neuromodulation of cervical excitatory interneurons (eINs) to improve functional respiratory recovery in chronic cSCI. Cervical eINs, crucial for acute injury recovery, showed no reduction in numbers at 8- and 12-weeks post injury, highlighting their potential as neuromodulatory targets in the chronic phase. Targeted chemogenetic activation of these cervical eINs significantly improved breathing at 6- and 12-weeks post-cSCI. Repeated stimulation induced dendritic plasticity in respiratory spinal neurons without altering soma size. Notably, stimulation-mediated recovery at 12 weeks was comparable to that observed at 6 weeks underscoring the sustained efficacy of this approach. These findings highlight the potential of targeted neuromodulation of spinal interneurons to improve breathing in the chronic phase of SCI.</div></div><div><h3>Teaser</h3><div>Targeted stimulation of spinal neurons improves breathing long after cervical spinal cord injury, offering new hope for treatments.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107007"},"PeriodicalIF":5.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329815","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}