Cellular and Molecular Neurobiology最新文献_第9页

Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy. 一氧化氮供体通过抑制HMGB1-ATG5介导的内皮细胞减轻心脏骤停引起的血脑屏障损伤。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-03-06 DOI: 10.1007/s10571-026-01706-w

Pengyu Duan, Yonghong Bi, Weiyu Feng, Zhehao Jin, Yao Meng, Hangbing Li, Xiaoyan Li, Lan Luo, Xiangcheng Zhao, Bing Zhang

{"title":"Nitric Oxide Donor Alleviates Cardiac Arrest Induced Blood Brain Barrier Injury by Inhibiting HMGB1-ATG5 Mediated Endothelial Autophagy.","authors":"Pengyu Duan, Yonghong Bi, Weiyu Feng, Zhehao Jin, Yao Meng, Hangbing Li, Xiaoyan Li, Lan Luo, Xiangcheng Zhao, Bing Zhang","doi":"10.1007/s10571-026-01706-w","DOIUrl":"10.1007/s10571-026-01706-w","url":null,"abstract":"Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) often cause severe neurological deficits due to ischemia–reperfusion (I/R) injury, marked by systemic inflammation, blood–brain barrier (BBB) dysfunction, and excessive autophagy. JS-K, a nitric oxide-releasing prodrug, has shown cytoprotective effects, but its role in CA-induced brain injury remains unclear. Here, we investigated the therapeutic potential of JS-K in a mouse CA/CPR model and an in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model. JS-K treatment improved neurological outcomes, preserved BBB function, and prolonged survival. Mechanistically, JS-K preserved tight junction proteins and improved BBB function and suppressed endothelial autophagy in vivo and in vitro. Further analyses revealed that HMGB1, after nuclear-cytoplasmic translocation, interacted with ATG5, inducing excessive autophagy and BBB injury. JS-K inhibited HMGB1 translocation, reduced HMGB1-ATG5 interaction, and consequently mitigated autophagy-driven BBB dysfunction. Notably, ATG5 silencing failed to enhance JS-K’s protective effects, supporting that JS-K acts at least in part through the HMGB1-ATG5 axis. These findings identify JS-K as a promising therapeutic agent that targets HMGB1-mediated autophagy to protect BBB function after cardiac arrest.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the Glioblastoma Microenvironment: AI-Driven Analysis of Cellular MRI Signatures for Targeted Therapy. 解码胶质母细胞瘤微环境：人工智能驱动的靶向治疗细胞MRI特征分析。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-03-05 DOI: 10.1007/s10571-026-01705-x

Yao Sun, Kai Wang, Tiantao Ye

{"title":"Decoding the Glioblastoma Microenvironment: AI-Driven Analysis of Cellular MRI Signatures for Targeted Therapy.","authors":"Yao Sun, Kai Wang, Tiantao Ye","doi":"10.1007/s10571-026-01705-x","DOIUrl":"10.1007/s10571-026-01705-x","url":null,"abstract":"Glioblastoma (GB), the most aggressive primary brain tumor, is characterized by profound inter- and intratumoral heterogeneity and a highly immunosuppressive tumor microenvironment (TME), both of which contribute to its poor prognosis and resistance to conventional therapies. The dynamic interplay between malignant cells and diverse TME constituents including immune cells, neural elements, and extracellular matrix components drives tumor progression, clonal evolution, and therapeutic failure. Traditional treatment modalities such as surgery, radiotherapy, and chemotherapy often fall short due to their inability to address the spatial and temporal complexity of the TME. Recent advances in artificial intelligence (AI) and cellular MRI profiling offer promising avenues for decoding the GB microenvironment at unprecedented resolution. By integrating AI-driven analysis of cellular MRI signatures, researchers can identify distinct microenvironmental niches and resistant subclones, enabling the development of targeted therapies that simultaneously disrupt tumor cells and their supportive ecosystems. This approach holds potential to overcome current therapeutic limitations and pave the way for personalized, microenvironment-informed interventions in GB management.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-Dependent Dynamics of Behavioural and Neuropathological Changes in an A53T Alpha-Synuclein Mouse Model of Parkinson's Disease. A53T α -突触核蛋白帕金森病小鼠模型中行为和神经病理变化的性别依赖动力学

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-03-04 DOI: 10.1007/s10571-026-01707-9

Maider Zubelzu, Raphaelle Bidgood, Ane Murueta-Goyena, José Ángel Ruiz-Ortega, José Vicente Lafuente, Teresa Morera-Herreras

{"title":"Sex-Dependent Dynamics of Behavioural and Neuropathological Changes in an A53T Alpha-Synuclein Mouse Model of Parkinson's Disease.","authors":"Maider Zubelzu, Raphaelle Bidgood, Ane Murueta-Goyena, José Ángel Ruiz-Ortega, José Vicente Lafuente, Teresa Morera-Herreras","doi":"10.1007/s10571-026-01707-9","DOIUrl":"10.1007/s10571-026-01707-9","url":null,"abstract":"Parkinson’s disease (PD) is characterised by progressive dopaminergic neurodegeneration, alpha-synuclein (α-syn) aggregation, and neuroinflammation. Clinical and experimental studies suggest that sex influences disease onset, progression, and treatment response, yet its impact on α-syn-mediated pathology remains incompletely understood. In this study, we investigated sex-dependent progression of behavioural and neuropathological alterations in a mouse model overexpressing A53T α-syn. Male and female C57BL/6J mice received bilateral intranigral injections of adeno-associated viral vectors encoding mutant A53T α-syn or empty vectors. Motor performance was assessed at 60 and 120 days post-surgery using open field, wire hang, pole, and balance beam tasks complemented by automated behavioural analysis (DeepLabCut, SimBA). Brains were processed for immunohistochemical evaluation of α-syn accumulation, tyrosine hydroxylase (TH) expression, axonal integrity, and glial activation. A53T α-syn overexpression induced early subtle motor deficits primarily in males, accompanied by increased immobility on the balance beam despite preserved substantia nigra compacta neuron counts. By 120 days, striatal TH immunoreactivity was markedly reduced in α-syn mice. An integrated axonal degeneration index, combining TH optical density and swelling counts, revealed a faster progression of striatal axonopathy in males. Both sexes showed enhanced striatal astrogliosis, indicating α-syn-driven neuroinflammation independent of sex. These findings identify early axonal degeneration and reactive astrogliosis as key pathological events preceding neuronal loss in A53T α-syn mice. Importantly, the pronounced male vulnerability highlights sex as a critical biological variable in modelling PD progression and in developing precision-based neuroprotective strategies.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Dopamine D1-Like Receptor Agonist Ameliorates Traumatic Brain Injury Through its Immunosuppressive Effects. 多巴胺d1样受体激动剂通过其免疫抑制作用改善创伤性脑损伤。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-28 DOI: 10.1007/s10571-026-01690-1

Mohammed E Choudhury, Ayane Takenaga, Haruto Yamamoto, Hiroto Yamauchi, Emiri Koga, Naoki Abe, Noriyuki Miyaue, Shirabe Matsumoto, Keisuke Sekiya, Akari Kusakawa, Naohito Tokunaga, Koichi Tanaka, Takeharu Kunieda, Masahiro Nagai, Junya Tanaka, Tasuku Nishihara

{"title":"A Dopamine D1-Like Receptor Agonist Ameliorates Traumatic Brain Injury Through its Immunosuppressive Effects.","authors":"Mohammed E Choudhury, Ayane Takenaga, Haruto Yamamoto, Hiroto Yamauchi, Emiri Koga, Naoki Abe, Noriyuki Miyaue, Shirabe Matsumoto, Keisuke Sekiya, Akari Kusakawa, Naohito Tokunaga, Koichi Tanaka, Takeharu Kunieda, Masahiro Nagai, Junya Tanaka, Tasuku Nishihara","doi":"10.1007/s10571-026-01690-1","DOIUrl":"10.1007/s10571-026-01690-1","url":null,"abstract":"Traumatic brain injury (TBI) causes progressive nervous tissue degeneration long after the initial injury due to secondary neuroinflammatory reactions. G protein-coupled dopamine D1-like receptors, which elevate intracellular cAMP levels, have been shown to mediate the suppressive effects on lipopolysaccharide (LPS)-induced proinflammatory activation of microglia and macrophages. The present study investigated whether or not the D1-like receptor-specific agonist SKF-81297 (SKF) administered intraperitoneally once daily for 3days starting 1 h after TBI could ameliorate TBI in a rat model of stab wounds in the forebrain. SKF reduced the volume of TBI-induced brain tissue loss, increased mobile activity, and ameliorated cognitive dysfunction two months after TBI. A single dose of SKF suppressed the expression of IL-1β and TNFα in brain tissue by reducing oxidative injury at 24 h post-TBI. SKF decreased the energy metabolism of microglia, macrophages, and neutrophils in TBI brain. SKF prevented LPS-induced translocation of NFκB into the nuclei of primary cultured microglia. The agonist clenbuterol (CLB) for adrenergic β2 receptor, another Gs-linked GPCR, exerted comparable ameliorative effects in TBI model rats by suppressing neuroinflammation. In summary, SKF may exert anti-inflammatory effects by suppressing the NFkB pathway through increasing cAMP similarly to CLB and also by decreasing energy metabolism of inflammatory cells, leading to amelioration of TBI-induced brain degeneration.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease. 纤溶系统在阿尔茨海默病中的双刃剑效应。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-27 DOI: 10.1007/s10571-026-01699-6

Mingqing Tang, Meimei Liang, Xianying Zhang, Chunzhan Hong, Lichao Ye

{"title":"The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.","authors":"Mingqing Tang, Meimei Liang, Xianying Zhang, Chunzhan Hong, Lichao Ye","doi":"10.1007/s10571-026-01699-6","DOIUrl":"10.1007/s10571-026-01699-6","url":null,"abstract":"Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is fundamentally driven by dysregulation between amyloid-β (Aβ) production and clearance. Although multiple Aβ clearance pathways have been reported, the fibrinolytic system remains the only enzymatically validated degradation route. Notably, a striking paradox is emerging: fibrinolytic agents exhibit both neuroprotective and AD-promoting effects in clinical observations. This duality necessitates urgent investigation into the fibrinolytic system's double-edged sword mechanism in AD pathogenesis. This review provides the first comprehensive analysis of the fibrinolytic system's dichotomous regulatory functions in AD progression, summarizes current advancements in the pathogenesis and therapeutic interventions, and proposes novel research directions. By resolving this molecular paradox, we aim to accelerate transformative breakthroughs in AD prevention and precision medicine strategies. Fibrinolytic System: Neuroprotection vs. Pathogenesis. The fibrinolytic system alleviates AD by directly degrading Aβ and indirectly improving the microenvironment of the central nervous system and cerebrovascular system. Meanwhile, this system also accelerates AD by promoting neuroinflammation and tau hyperphosphorylation.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroradiological Phenotype Expansion of the Siddiqi Syndrome: A Case Report. Siddiqi综合征的神经放射学表型扩展1例报告。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-27 DOI: 10.1007/s10571-026-01672-3

Paula Trilla, Laia Rodriguez-Revenga, Aurora Sanchez, Irene Madrigal, Jose Cesar Milisenda, Esteban Muñoz, Maria Isabel Alvarez-Mora

{"title":"Neuroradiological Phenotype Expansion of the Siddiqi Syndrome: A Case Report.","authors":"Paula Trilla, Laia Rodriguez-Revenga, Aurora Sanchez, Irene Madrigal, Jose Cesar Milisenda, Esteban Muñoz, Maria Isabel Alvarez-Mora","doi":"10.1007/s10571-026-01672-3","DOIUrl":"10.1007/s10571-026-01672-3","url":null,"abstract":"Siddiqi syndrome is a rare autosomal recessive deafness-dystonia disorder caused by pathogenic variants in the FITM2 gene. To date, only 5 unrelated families have been reported in the literature carrying loss-of-function variants in FIMT2 gene. In this report, we describe a 29-year-old woman with compound heterozygous novel variants identified by trio-based exome sequencing. She carries the paternally inherited delins variant c.158_161delinsTCAT, p.(Arg53_Asn54delinsLeuIle) and the maternally inherited frameshift variant c.567del, p.(Thr190ProfsTer9) in FITM2 gene. The patient exhibits the main features of the disease, including deafness, intellectual disability, regression of motor skills and poor overall growth. Additionally, she presents with spastic paraplegia which supports recent phenotypic expansion. We describe for the first time, novel brain magnetic resonance imaging signal alterations, not previously associated with this disorder. These neuroimaging findings may provide new insights into the neurological manifestations of Siddiqi syndrome. This case expands the phenotypic and molecular spectrum of FITM2 associated disease and emphasizes the adult-features of this syndrome.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease. d -丝氨酸：脑功能、系统稳态和疾病中的多功能神经调节剂。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-24 DOI: 10.1007/s10571-026-01696-9

Jing Wang, Yujin Guo, Wenxiu Han, Hailiang Zhang, Pei Jiang

{"title":"D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.","authors":"Jing Wang, Yujin Guo, Wenxiu Han, Hailiang Zhang, Pei Jiang","doi":"10.1007/s10571-026-01696-9","DOIUrl":"10.1007/s10571-026-01696-9","url":null,"abstract":"D-serine is an endogenous D-amino acid and a crucial co-agonist for the N-methyl-D-aspartate (NMDA) receptor, well known as a key regulator of synaptic plasticity, learning, and memory. This review summarizes recent advances that extend beyond this canonical role, positioning D-serine as a dynamic nexus linking brain function to systemic homeostasis. We explore its spatiotemporal dynamics in synaptic microdomains, sophisticated epigenetic and transcriptional regulation, and emerging role as a metabolic sensor linking cellular energetics to neuronal signaling. Furthermore, we highlight novel non-canonical signaling pathways, including its function as a ligand for the glutamate delta-1 receptor (GluD1) and its direct role in peripheral organs like the gut and kidney. The pathophysiological implications of disrupted D-serine homeostasis are detailed across a spectrum of CNS disorders—from schizophrenia and Alzheimer’s disease (AD) to addiction and neuropathic pain—as well as in peripheral conditions including diabetic complications and osteoporosis. Finally, we discuss the translational potential of targeting D-serine pathways through innovative therapeutic strategies—such as serine racemase (SR) modulators, D-amino acid oxidase (DAAO) inhibitors, and gene therapy—and its promise as a biomarker for personalized medicine in neurology and psychiatry.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebral Hypoperfusion Causes Behavioral Changes and Impairs the Rod Photoreceptor Pathway in the Retina of Aged Mice. 脑灌注不足引起老年小鼠视网膜的行为改变和杆状光感受器通路的损害。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-23 DOI: 10.1007/s10571-026-01698-7

Spencer Talmage Barney, Daniela Becerril, Sheelu Monga, Samantha Flores, Audrey Lee, Marlon Fraga Mattos, Ross M Perez, Frank W Blixt, Michael Maniskas, Shuning Huang, Hongyu Wu, Chunfeng Tan, Louise D McCullough, Elizabeth Zuniga-Sanchez, Jose Felix Moruno-Manchon

{"title":"Cerebral Hypoperfusion Causes Behavioral Changes and Impairs the Rod Photoreceptor Pathway in the Retina of Aged Mice.","authors":"Spencer Talmage Barney, Daniela Becerril, Sheelu Monga, Samantha Flores, Audrey Lee, Marlon Fraga Mattos, Ross M Perez, Frank W Blixt, Michael Maniskas, Shuning Huang, Hongyu Wu, Chunfeng Tan, Louise D McCullough, Elizabeth Zuniga-Sanchez, Jose Felix Moruno-Manchon","doi":"10.1007/s10571-026-01698-7","DOIUrl":"10.1007/s10571-026-01698-7","url":null,"abstract":"Gradual reduction of cerebral blood flow occurs with aging, and it is a major cause of vascular dementia, a group of dementias with a cerebrovascular component. Interestingly, patients who have suffered a vascular insult may develop retinopathy, which may occur as an early symptom of vascular dementia. Several rodent models using young animals have been generated to mimic retinopathy caused by cerebral hypoperfusion; however, given that aging is an important factor in developing vascular dementia and hypoperfusion retinopathy, we propose to use aged (17-month-old) mice in a model of cerebral hypoperfusion. In this model, we implant two metallic micro-coils (0.16 mm inner diameter) around both common carotid arteries. We found that two months after surgery, aged mice with bilateral carotid artery stenosis (BCAS) showed hyperactivity-like behavior, cognitive deficits, and demyelination, which are pathological features in patients with vascular dementia. We also found that the retina of BCAS mice showed important morphological changes, such as reduced area of the outer synaptic layer, retraction of rod photoreceptor terminals, and increased sprouting of rod bipolar cells. BCAS mice also showed reduced in vivo retinal responses to different light intensities. Our study is the first to propose using aged mice in a model of hypoperfusion retinopathy, which is relevant to identifying the molecular mechanisms underlying vision loss with cerebral hypoperfusion.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial Autofluorescence in the Brain and Retina is Dynamically Modulated by Systemic Inflammation. 大脑和视网膜的小胶质细胞自身荧光受到全身炎症的动态调节。

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-22 DOI: 10.1007/s10571-026-01704-y

Mary Slayo, Hasan Ul Banna, Ying Zhi Cheong, Soniya Xavier, Kylie M Quinn, Luba Sominsky, Loretta Vocale, Philipp Reineck, Brant C Gibson, Blanca Del Rosal, Sarah J Spencer

{"title":"Microglial Autofluorescence in the Brain and Retina is Dynamically Modulated by Systemic Inflammation.","authors":"Mary Slayo, Hasan Ul Banna, Ying Zhi Cheong, Soniya Xavier, Kylie M Quinn, Luba Sominsky, Loretta Vocale, Philipp Reineck, Brant C Gibson, Blanca Del Rosal, Sarah J Spencer","doi":"10.1007/s10571-026-01704-y","DOIUrl":"10.1007/s10571-026-01704-y","url":null,"abstract":"The retina-an extension of the central nervous system-contains microglia that survey and respond to injury or pathogens. In response to their environmental milieu, these cells accumulate autofluorescent material likely reflective of cellular debris. Measuring these autofluorescence changes may be a useful tool for early diagnosis of brain-related inflammatory conditions or diseases by imaging the eye. To assess this, we gave Wistar rats a systemic immune challenge with lipopolysaccharide (LPS; 250 µg/kg, intraperitoneally) and examined autofluorescence characteristics of the microglia in brain and eye using confocal microscopy. Initial flow cytometry experiments verified that isolated microglia are highly autofluorescent compared to cells in immune-related organs such as spleen. In immunolabelled brain sections (arcuate, hippocampus, retrosplenial cortex), astrocytes, neurons, and microglia all displayed significant autofluorescence, with microglia displaying greatest levels. LPS led to predicted changes in microglial morphology in the brain and this was accompanied by an increase in the number of individual autofluorescent aggregates but a reduction in the total volume, indicative of changes in the dynamics of the material. While there were similarities in the microglial response to LPS in the retina, and the total volume of autofluorescence aggregates was also reduced, retinal autofluorescence changes did not simply predict those seen in brain. These findings suggest that the relationship between immune challenge states and autofluorescence accumulation is dynamic and complex. Understanding the role of microglia in accumulating and metabolising this autofluorescent material may assist our understanding of disease states and how they influence retina and brain.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unravelling Synaptic and Metabolic Mechanisms of Cognitive Resilience in Asymptomatic Alzheimer's Disease Across Two Alzheimer's Disease Cohorts. 在两个阿尔茨海默病队列中揭示无症状阿尔茨海默病认知弹性的突触和代谢机制

IF 7.4 4区医学

Cellular and Molecular Neurobiology Pub Date : 2026-02-22 DOI: 10.1007/s10571-026-01700-2

Rümeysa Aksu, Hatice Büşra Lüleci, Tunahan Çakır

{"title":"Unravelling Synaptic and Metabolic Mechanisms of Cognitive Resilience in Asymptomatic Alzheimer's Disease Across Two Alzheimer's Disease Cohorts.","authors":"Rümeysa Aksu, Hatice Büşra Lüleci, Tunahan Çakır","doi":"10.1007/s10571-026-01700-2","DOIUrl":"10.1007/s10571-026-01700-2","url":null,"abstract":"Asymptomatic Alzheimer's Disease (AsymAD) is a preclinical stage of Alzheimer's Disease (AD) identified by amyloid plaques and neurofibrillary tangles in cognitively normal individuals and offers essential understanding for early diagnosis and treatment of AD. To uncover molecular insights into AsymAD, RNA sequencing (RNA-seq) datasets from two different consortia, ROSMAP (Religious Orders Study and Memory and Aging Project) and MSBB (Mount Sinai Brain Bank), were investigated. The individuals in the datasets were grouped into AD and AsymAD based on clinical and neuropathological criteria. Differentially expressed genes (DEGs), differentially expressed transcripts (DETs), and differentially used transcripts (DUTs) were identified between AD and AsymAD samples. The results were interpreted through functional enrichment analysis and compared with the predefined lists of AD-related and learning-memory-cognition-related genes, and genes from an independent mouse dataset. The genes from the list of DEGs, DETs and DUTs were mapped onto a human protein-protein interaction network, revealing subnetworks associated with AsymAD. This led to the discovery of biomarker candidate genes: NRXN3, DGKB, ADAMTS2, GNG4, ENPP5, PCOLCE, COL25A1, COL26A1, MRPL1, and MRPL30. This study introduces an innovative approach by including DETs and DUTs in the analyses, beyond the standard focus on DEGs, pointing out comprehensive insights into the molecular mechanisms of AsymAD. In addition, combining the results of the subnetwork analysis from DEGs, DETs, and DUTs provided a new perspective to AsymAD and resulted in the discovery of further important genes, which can pave the way for early detection and intervention of AD.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0