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":"RNA helicase maheshvara interacts with TDP-43 and exacerbates neurodegeneration in Drosophila model of amyotrophic lateral sclerosis.","authors":"Pranjali Pandey, Rituparna Das, Harshita Yadav, Ashim Mukherjee, Mousumi Mutsuddi","doi":"10.1016/j.nbd.2025.107036","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.107036","url":null,"abstract":"<p><p>Drosophila maheshvara (mahe) encodes a conserved DEAD box RNA helicase that regulates various important signaling pathways like Notch and JAK/STAT, pathways that have been functionally implicated in neuronal development. In order to identify novel modulators of mahe as well as to unravel its role in neurodegenerative disorders, a genetic modifier screen using Drosophila models of neurodegenerative disorders was carried out. From this screen, we identified mahe to be a potent modifier of TDP-43 mediated proteinopathy in Drosophila model of Amyotrophic Lateral Sclerosis (ALS). We demonstrate that Mahe genetically interacts and associates with cytosolic hyperphosphorylated toxic aggregates of TDP-43 leading to enhanced TDP-43 mediated neurodegenerative phenotype. Increased autophagy, cytoskeletal disruption, and FMRP-mediated translational repression of neuronal target Futsch were observed, potentially contributing to neuronal dysfunction. The current study indicates a strong interaction of mahe and TDP-43 (TARDBP) resulting in augmentation of TDP-43 mediated neurodegenerative phenotypes which parallels ALS clinical pathology.</p>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":" ","pages":"107036"},"PeriodicalIF":5.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682805","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":"Attenuated orexinergic signaling underlies sleep-wake problems in a Mecp2-null mouse model of Rett syndrome.","authors":"Kotaro Yuge, Tomoyuki Takahashi, Yukie Kawahara, Yusuke Sakai, Takahiro Sato, Tatsuyuki Kakuma, Akinori Nishi, Toyojiro Matsuishi, Yushiro Yamashita","doi":"10.1016/j.nbd.2025.107035","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.107035","url":null,"abstract":"<p><p>Rett syndrome (RTT) is a severe neurodevelopmental disorder mainly caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Previous studies reported sleep problems characterized by changes in architecture and sleep-wake patterns in both RTT patients and animal models of RTT. However, little is known about the neural mechanisms underlying the sleep-wake problems in humans or animals. In this study, Mecp2-null mice showed decreased locomotor activity during the dark period of light-dark conditions, but behaviorally showed no significant deficits in the photic regulation of circadian rhythms. Piezoelectric monitoring demonstrated that Mecp2-null mice slept mainly in short bouts and spent less time in long sleep bouts than their wild-type littermates. Electroencephalographic analysis revealed that Mecp2-null mice had very short, frequent periods of sleep during the dark period, indicating frequent state transitions between wakefulness and non-REM sleep during the dark period. Greater numbers of short sleep bouts during the dark period than during the light period could indicate that Mecp2-null mice spent more time napping during their typically active period. MeCP2 deficiency affected the expression of several neuromodulator genes in hypothalamic regions. Specifically, the expression of hypocretin/orexin receptor (Hcrtr) 1 and 2 genes were significantly lower in several brain regions of Mecp2-null mice, and these mice exhibited attenuated hypocretin/orexin receptor signaling in in vivo microdialysis studies of hypocretin/orexin receptor agonist YNT-185. These results indicate disturbance of the hypocretin/orexin system in Mecp2-null mice, which might cause sleep-wake problems such as increased somnolence in the active phase.</p>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":" ","pages":"107035"},"PeriodicalIF":5.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675322","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":"Double-edged sword effect of Sutterella in neurological disorders: implications for the gut-brain axis and neuroimmune interactions","authors":"Samin Davoody ,&nbsp;Hossein Halimi ,&nbsp;Alireza Zali ,&nbsp;Hamidreza Houri ,&nbsp;Serge Brand","doi":"10.1016/j.nbd.2025.107032","DOIUrl":"10.1016/j.nbd.2025.107032","url":null,"abstract":"<div><div>The genus <em>Sutterella</em>, a group of bile-resistant microaerophilic gram-negative bacteria, has emerged as a key player in gut-brain axis communication, with significant yet complex implications for neurological and psychiatric disorders. This study synthesizes current evidence on <em>Sutterella</em>'s dual role in modulating immune responses and neuroinflammation, highlighting its context-dependent effects across Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), multiple sclerosis (MS), migraine, epilepsy, autoimmune encephalomyelitis (AE), and depression. While <em>Sutterella</em> exhibits pro-inflammatory properties, such as inducing cytokines (e.g., IL-6 and TNF-α) and degrading immunoglobulin A (IgA), it also demonstrates immunomodulatory potential, including anti-inflammatory IL-10 induction. Recent studies underscore <em>Sutterella</em>’s direct and indirect involvement in neuropathological processes through its influence on systemic inflammation, barrier permeability, tryptophan metabolism, and glial activation. In AD and PD, its abundance correlates with disease severity and key molecular markers such as amyloid burden and oxidative stress. In ASD and depression, <em>Sutterella</em> has been linked to neuroinflammatory cascades and behavioral dysregulation, potentially mediated through lipopolysaccharide (LPS)-associated immune activation. Furthermore, the presence of <em>Sutterella</em> has shown predictive utility in migraine and schizophrenia cohorts, reinforcing its relevance as both a potential biomarker and therapeutic target. This review underscores the need for standardized methodologies, mechanistic studies, and longitudinal cohorts to clarify <em>Sutterella</em>'s causal contributions. By integrating preclinical and clinical data, we propose <em>Sutterella</em> as a potential biomarker and therapeutic target, emphasizing the importance of personalized approaches in microbiota-based interventions for neurological and psychiatric disorders.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107032"},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653658","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":"Brain connectivity regions of lesions causing focal to bilateral tonic-clonic seizures correlates with gene expression.","authors":"Yuting Sun, Huoyou Hu, Lu Qin, Zirong Chen, Shujun Su, Qin Zhou, Bailing Qin, Xiaochuan Fu, Jinou Zheng","doi":"10.1016/j.nbd.2025.107031","DOIUrl":"https://doi.org/10.1016/j.nbd.2025.107031","url":null,"abstract":"<p><p>Focal to bilateral tonic-clonic seizures (FBTCS) is one of the most severe forms of seizures. Why lesions in some brain areas result in FBTCS while lesions in other areas do not? This study aimed to examine whether the locations of lesions causing FBTCS were mapped to specific brain regions and to explore correlation between the specific brain regions and gene expression. A retrospective study was conducted involving 25 patients diagnosed with FBTCS. The lesion network mapping method was employed, utilizing a large database of resting-state fMRI scans to detect brain regions connected to lesions causing FBTCS. Additionally, gene expression profiles related to the specific brain regions of FBTCS were examined using transcriptome neuroimaging association analysis. The lesion locations of FBTCS were found to be heterogeneous, but connected to the specific brain regions. The cerebellum, thalamus, cingulate cortex, and middle frontal gyrus were identified as hubs of the specific brain regions as they were the areas that were both functionally connected to 96 % of lesions, as well as significantly different in connectivity. Moreover, the specific brain regions were colocalized with whole-brain gene expression in the biological processes with synaptic functions, ion channel activity, lysosome and comorbidity pathway. This study suggests that lesions causing FBTCS mapped to the specific brain regions, providing insight into the causal neuroanatomical foundation in FBTCS. Decoding the specific brain regions of FBTCS through transcriptomic may indicate the presence of multiscale interactions in FBTCS, promoting our understanding of the genetic molecular mechanism of FBTCS.</p>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":" ","pages":"107031"},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668053","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":"Persistent Na+ and M-type K+ currents opposingly control spike gain in CA3 pyramidal cells","authors":"Idit Tamir,&nbsp;Yoel Yaari","doi":"10.1016/j.nbd.2025.107034","DOIUrl":"10.1016/j.nbd.2025.107034","url":null,"abstract":"<div><div>Neural firing response gain and spike threshold are critical intrinsic cell properties that define input-output relations in neurons. Alterations of these cellular properties in hippocampal pyramidal cells (PCs) may strongly influence network dynamics in health and disease. Here we investigated how specific voltage-gated conductance affect these properties in adult rat CA3 pyramidal cells (PCs) in hippocampal slices under near-physiological conditions. We examined currents activated at near-threshold potential – persistent sodium current (<em>I</em>_NAP), T-type Ca²⁺ current (<em>I</em>_CaT), M-type K⁺ current (<em>I</em>_M), SK Ca²⁺ − dependent current <em>(I</em>_SK)_, and h-type cationic current (<em>I</em>_h) through pharmacological modulation and analysis of resulting changes. CA3 PCs showed high heterogeneity in firing response gain, likely reflecting individual variations in active conductance at rest. Blocking <em>I</em>_NAP by riluzole decreased firing response gain, an effect associated with a reduction in the depolarizing shift (DS) underlying evoked spike trains. Conversely, blocking <em>I</em>_M with XE991 markedly increased firing response gain, decreased the DS, increased input resistance, and lowered spike threshold. Enhancing <em>I</em>_M by retigabine produced opposite effects. Blocking <em>I</em>_SK with apamin moderately augmented firing response gain, while blocking <em>I</em>_CaT and <em>I</em>_h exerted no effect on discharge.</div><div>Our findings identify <em>I</em>_NaP and <em>I</em>_M as key determinants of spike response gain and threshold of CA3 PCs, suggesting that modulators of these currents may effectively modify neuronal input-output relations in both normal and pathological states of hippocampal hypo- or hyperexcitability.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107034"},"PeriodicalIF":5.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663117","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":"Pathological α-synuclein perturbs nuclear integrity","authors":"Michael Millett ,&nbsp;Allison Comite ,&nbsp;Elisabeth Martin Castosa ,&nbsp;Anika Heuberger ,&nbsp;Preston Wagner ,&nbsp;Ignacio Gallardo ,&nbsp;Jessica Reinhardt ,&nbsp;Nicole Chambers ,&nbsp;Dominic Hall ,&nbsp;Evan Miller ,&nbsp;Douglas Nabert ,&nbsp;Barbara Balsamo ,&nbsp;Stefan Prokop ,&nbsp;Mark Moehle","doi":"10.1016/j.nbd.2025.107028","DOIUrl":"10.1016/j.nbd.2025.107028","url":null,"abstract":"<div><div>Pathological aggregates of α-synuclein are a hallmark of a group of neurodegenerative disorders collectively termed synucleinopathies. The physiological function of α-synuclein, and the detrimental effects of the pathological variants of α-synuclein have been widely debated, but recent evidence has suggested an emerging consensus on a critical role for α-synuclein in regulating synaptic function. However, a controversial role for α-synuclein in nuclear function in both normal and pathogenic states has been proposed, and the degree to which α-synuclein localizes within the nucleus and subsequent impact on the nucleus are poorly understood. To begin to address this controversy, we employed synucleinopathy murine and cell culture models, as well as postmortem human Lewy Body Dementia tissue to elucidate the extent to which pathological α-synuclein localizes within the nuclear compartments, and the downstream consequences of this localization. We observed pathological aggregation of α-synuclein within the nucleus in both murine models and human postmortem Lewy Body Dementia cortex via quantitative super resolution microscopy. In both mouse and human brain tissue the presence of α-synuclein in the nucleus correlated with abnormal morphology of nuclei. This pathological accumulation of α-synuclein in the nucleus was not observed in control mice, human tissue without pathology, or control cells. We subsequently examined the correlated changes in nuclear function with pathological accumulation of α-synuclein in the nucleus. Synucleinopathy models displayed increased levels of the DNA damage marker 53BP1. Furthermore, cells with pathological α-synuclein exhibited elevated markers of nuclear envelope damage and abnormal expression of nuclear envelope repair markers. Our cell culture data also suggests altered RNA localization in response to pathological α-synuclein accumulation within the nucleus. Lastly, we show that nuclear Lewy-like pathology leads to increased sensitivity to nuclear targeted toxins. Taken together, these results rigorously illustrate nuclear localization of pathological α-synuclein with super resolution methodology and provide novel insight into the ensuing impact on nuclear integrity and function.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107028"},"PeriodicalIF":5.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649978","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":"Cell-to-cell transmission of IAPP aggregates in T2DM induces neuronal death by triggering oxidative stress and ferroptosis","authors":"Honglin Zheng ,&nbsp;Yapei Yuan ,&nbsp;Na Zhang ,&nbsp;Hang Zhang ,&nbsp;Suying Duan ,&nbsp;Chenyang Liu ,&nbsp;Yaochong Zhang ,&nbsp;Qiang Li ,&nbsp;Han Liu ,&nbsp;Mibo Tang ,&nbsp;Haiyang Luo ,&nbsp;Yuming Xu","doi":"10.1016/j.nbd.2025.107015","DOIUrl":"10.1016/j.nbd.2025.107015","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of neurodegenerative diseases, yet the underlying mechanisms remain elusive. A hallmark feature of T2DM is the amyloid deposition of islet amyloid polypeptide (IAPP) in the pancreas, which may contribute to both pancreatic dysfunction and systemic pathological processes. In this study, we aimed to explore the role of IAPP aggregates as a possible mechanistic link in diabetes-associated neurodegeneration. Using co-culture systems with fluorescently labeled IAPP fibrils, we observed IAPP aggregates transfer between neurons via tunneling nanotubes (TNTs). RNA-seq analysis demonstrated that exposure to IAPP amyloid fibrils triggered substantial alterations in transcriptional profiles, enriching pathways related to oxidative phosphorylation and reactive oxygen species (ROS) production. Mechanistic investigations further showed that IAPP fibrils led to increased ROS levels, mitochondrial dysfunction, and ultimately neuronal death through ferroptosis. Specially, IAPP fibrils disrupted the p62-Keap1 interaction, blocking NRF2 nuclear translocation and altering the expression of ferroptosis-related proteins. Overall, these findings highlight the role of IAPP aggregates in T2DM associated with neurodegeneration, providing new insights into potential therapeutic targets for the relationship between these diseases.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107015"},"PeriodicalIF":5.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649977","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":"Hearing the call of mitochondria: Insight into its role in sensorineural hearing loss","authors":"Haojia He ,&nbsp;Zhuoxue Han ,&nbsp;Shuai Cheng ,&nbsp;You Zhou","doi":"10.1016/j.nbd.2025.107030","DOIUrl":"10.1016/j.nbd.2025.107030","url":null,"abstract":"<div><div>Sensorineural hearing loss (SNHL) is a prevalent and complex auditory disorder with a multifactorial pathogenesis, in which mitochondrial dysfunction plays a pivotal role. Mitochondria are abundantly localized in critical structures of the inner ear, where they not only provide the substantial energy required for auditory transduction but also regulate key cellular processes. Growing evidence suggests that mitochondrial impairment, characterized by excessive reactive oxygen species (ROS) generation, dysregulated inflammatory responses, disrupted apoptosis, and mitochondrial DNA (mtDNA) mutations, is closely linked to the onset and progression of SNHL. Recent advances in mitochondria-targeted therapeutic strategies, such as antioxidant delivery, promotion of mitochondrial biogenesis, and mitochondrial gene therapy, have shown promising preclinical results. However, significant challenges remain in translating these approaches into clinical practice, particularly in terms of targeted delivery, long-term efficacy, and potential side effects. This comprehensive review systematically examines the molecular mechanisms underlying mitochondrial involvement in SNHL pathogenesis, evaluates recent progress in mitochondria-targeted interventions, and discusses current limitations and future directions in this rapidly evolving field. By integrating current knowledge and identifying key research gaps, this review aims to provide a solid theoretical foundation and fresh perspectives for the development of effective therapeutic strategies for SNHL.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"213 ","pages":"Article 107030"},"PeriodicalIF":5.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626767","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}