Cellular and Molecular Neurobiology最新文献

{"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":"<p><p>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.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"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}

{"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":"<p><p>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.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"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}

{"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":"<p><p>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.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"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}

{"title":"Identification of Biomarkers Associated With Copper Metabolism in Ischemic Stroke Through Bulk RNA Sequencing and Mendelian Randomization Analysis.","authors":"Ruizhe Yang, Xin Zhou, Zhiheng Zhao, Jie Xu, Zhang Yang","doi":"10.1007/s10571-026-01697-8","DOIUrl":"10.1007/s10571-026-01697-8","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257492","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}

{"title":"Regional Molecular Diversity in Chronic Spinal Cord Injury.","authors":"Chan-Il Choi, Ha Neui Kim, Hyesook Yoon, Maja Radulovic, Whitney L Simon, Isobel A Scarisbrick","doi":"10.1007/s10571-026-01694-x","DOIUrl":"10.1007/s10571-026-01694-x","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257436","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}

{"title":"Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.","authors":"Sveva Dallere, Antonio Migheli, Alessandro Vercelli","doi":"10.1007/s10571-026-01676-z","DOIUrl":"10.1007/s10571-026-01676-z","url":null,"abstract":"<p><p>Alzheimer disease (AD), first described by Alzheimer and Perusini in the early twentieth century, is a devastating neurodegenerative disorder without a definitive cure. Unraveling the subcellular alterations underlying AD is essential to elucidate disease mechanisms, track progression, link cellular abnormalities to functional deficits, and develop therapeutic strategies aimed at preventing, slowing or reverting the disease course. Electron microscopy (EM) has been pivotal in this field since the 1960s, when Terry and Kidd characterized the ultrastructure of amyloid-beta (Aβ) deposits and paired helical filaments (PHFs) composed of hyperphosphorylated tau. Over the decades, conventional transmission and scanning EM have been complemented by advanced approaches such as volume EM (vEM), cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET). These techniques enable three-dimensional reconstructions, minimize fixation artifacts, and provide near-native, near-atomic resolution insights into AD pathology. EM has also revealed critical contributions of other subcellular compartments to AD pathogenesis, including synapses, mitochondria, lysosomes, the blood-brain barrier, iron deposits, and inflammatory machinery. Importantly, EM studies extend beyond human tissue, encompassing animal models, cell cultures, and synthetic assemblies, thereby allowing cross-system comparisons that highlight conserved pathological features. By integrating data from diverse experimental settings, EM provides a uniquely comprehensive view of the AD subcellular landscape. This makes it an indispensable tool not only for dissecting disease mechanisms but also for guiding the rational design of therapeutic molecules with potential disease-modifying effects. This review synthesizes the state of knowledge on EM-based studies of AD, emphasizing their central role in advancing both mechanistic understanding and translational approaches.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257497","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}

{"title":"Interactions Between Perioperative Anesthesia Management and Gut Microbiota: Current Research Advances.","authors":"Naiqi Jiang, Lei Wang, Xiaodi Chen, Cuicui Yu","doi":"10.1007/s10571-026-01701-1","DOIUrl":"10.1007/s10571-026-01701-1","url":null,"abstract":"<p><p>The gut microbiota (GM), a complex and diverse microbial community residing in the digestive tract, plays a pivotal role in human health and disease. Recent studies have revealed a strong association between the GM and overall health, with dysbiosis potentially contributing to conditions such as inflammation, infection, and obesity. As medical technology advances, anesthesia has become indispensable in surgical and clinical procedures. Emerging evidence highlights the bidirectional interactions between the GM and anesthesia, which may exert profound effects on human health. This review synthesizes the current knowledge on the mutual influences of perioperative anesthesia and the GM, discusses the potential mechanisms underlying anesthesia-induced dysbiosis, and proposes strategies for preventing and managing microbiota imbalances. Future research should prioritize elucidating the precise mechanisms of anesthetic modulation of the GM and exploring microbiota-targeted interventions with the aim of potentially optimizing postoperative recovery and long-term health.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218790","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}

{"title":"Cooperation of Transcription Factor PAX6 with Chromatin-Remodeling Complex BAF During Embryonic Development in Mammals.","authors":"Asya Azieva, Tatyana Vasilyeva, Oksana Maksimenko, Kseniya Davydenko, Rena Zinchenko, Andrey Marakhonov","doi":"10.1007/s10571-026-01692-z","DOIUrl":"10.1007/s10571-026-01692-z","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200377","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}

{"title":"Entorhinal Cholecystokinin in Alzheimer's Disease: Its Earliest Vulnerability and Rescue Effects Across Different Disease Stages in a Mouse Model.","authors":"Yixuan Sui, Nan Zhang, Xi Chen, Micky D Tortorella, Jufang He","doi":"10.1007/s10571-026-01689-8","DOIUrl":"10.1007/s10571-026-01689-8","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. The entorhinal cortex (Ent) is among the earliest affected regions, and its neuropeptide cholecystokinin (CCK) supports neocortical-associated memory. Although our previous work demonstrated that CCK treatment rescues cognition and neuroplasticity in aged AD mice, the correlations among CCK expression, synaptic function, and cognitive decline with aging remain poorly understood. Using 3xTg-AD mice (2-18 months), we performed stereological, histological, and molecular analyses to evaluate brain atrophy, neuronal loss, glial responses, and gene expression. Cognitive function was assessed using the novel object recognition test (NOR), motor learning was evaluated using the rotarod test, and synaptic integrity was measured via electrophysiological recordings. We also investigated the therapeutic potential of CCK-B receptor (CCK-BR) agonists on learning and memory and neuroplasticity across disease stages of AD. In 3xTg-AD mice, the Ent exhibits significant atrophy and excitatory neuronal loss as early as 7 months of age, confirming its role as one of the earliest and most severely affected regions in AD. CCK was downregulated earlier than other synaptic genes in the Ent and other brain regions. Cholecystokinin tetrapeptide (CCK-4) treatment rescued deficits in synaptic plasticity, cognition, and motor learning in 3xTg-AD mice across multiple disease stages. Long-term administration of HT-267, a CCK-BR agonist with a prolonged half-life, in young 3xTg-AD mice delayed cognitive decline, enhanced synaptic scaffolding, and restored long-term potentiation in both the cortex and hippocampus (HPC). Our findings identify CCK downregulation as an early biomarker in AD and demonstrate the therapeutic effects of CCK-BR agonists in mitigating cognitive and synaptic deficits from mild to severe disease stages. The ability of long-term CCK-4 analogue treatment to decelerate AD progression indicates its promise as an early intervention strategy.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12960918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194177","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}

{"title":"CREB2 Functions as a Central Mediator of Oxidative Neuronal Death Triggered by Microglial Glutamate Release Under Neuroinflammatory Conditions.","authors":"Uk Yeol Moon, Young Eun Kim, Huu Dat Nguyen, Hye Joung Choi","doi":"10.1007/s10571-026-01695-w","DOIUrl":"10.1007/s10571-026-01695-w","url":null,"abstract":"<p><p>Glutamate-induced oxidative cytotoxicity is a major driver of neuronal loss in neurodegenerative diseases, yet the upstream transcriptional regulators linking oxidative stress to neuronal death remain unclear despite the known involvement of the p53-GADD45α pathway. CREB2 (ATF4) is a stress-responsive transcription factor, but its role in microglia-mediated oxidative neurotoxicity has not been fully defined. Here, we investigated CREB2 function in oxidative glutamate toxicity using HT22 hippocampal neurons, primary mouse hippocampal cells, and a kainic acid (KA)-injected rat model. Oxidative stress was induced by glutamate, intracellular ROS levels were quantified with DCFDA, and the antioxidant N-acetylcysteine (NAC) was used to confirm oxidative dependency. Microglia-derived glutamate was assessed by stimulating BV2 cells with lipopolysaccharide (LPS) and applying glutamate-containing conditioned medium (LPS-CM) to HT22 cells. Exogenous glutamate robustly increased CREB2 expression in HT22 and primary neurons, accompanied by ROS accumulation and cell death, whereas NAC suppressed these effects. Inhibition of p53 by siRNA or pifithrin-α (PFT-α) attenuated glutamate-induced CREB2 upregulation, and CREB2 knockdown blocked GADD45α induction and protected neurons. In Vivo, KA injection caused robust CREB2 upregulation in the damaged CA3 region. Importantly, conditioned medium from LPS-activated BV2 microglia increased CREB2 expression and ROS levels in HT22 cells in an NAC-sensitive manner, supporting a glutamate-associated oxidative mechanism rather than receptor-mediated excitotoxicity. Collectively, these results suggest that CREB2 functions between upstream p53 signaling and downstream GADD45α activation as a redox-sensitive mediator of oxidative neuronal death, and may represent a potential therapeutic target in neurodegenerative diseases associated with oxidative stress and neuroinflammation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178059","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}