Frontiers in Cellular Neuroscience最新文献

{"title":"A novel method for reliably measuring miniature and spontaneous postsynaptic events in whole-cell patch clamp recordings in the central nervous system.","authors":"Martynas Dervinis, Guy Major","doi":"10.3389/fncel.2025.1598016","DOIUrl":"10.3389/fncel.2025.1598016","url":null,"abstract":"<p><p>Measurements of miniature postsynaptic currents (mPSCs) or potentials (mPSPs) in the soma of neurons of the central nervous system (CNS) provide a way of quantifying the synaptic function at the network level and, therefore, are routine in the neurophysiology literature. These miniature responses (or minis) are thought to be elicited by the spontaneous release of a single neurotransmitter vesicle, also called a quantum. As such, their measurement at the soma can potentially offer a technically straightforward way of estimating \"quantal sizes\" of central synapses. However, popular methods for detecting minis in whole-cell recordings fall short of being able to reliably distinguish them from background physiological noise. This issue has received very limited attention in the literature, and its scope as well as the relative performance of existing algorithms have not been quantified. As a result, solutions for reliably measuring the quantal size in somatic recordings also do not exist. As the first step in proposing and testing a potential solution, we developed and described a novel miniature postsynaptic event detection algorithm as part of our quantal analysis software called \"minis\". We tested its performance in detecting real and simulated minis in whole-cell recordings from pyramidal neurons in rat neocortical slices and compared it to two of the most-used mini detection algorithms. This benchmarking revealed superior detection by our algorithm. The release version of the algorithm also offers great flexibility via graphical and programming interfaces.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1598016"},"PeriodicalIF":4.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the brain and gut: neuroimmune mechanisms of neuroinflammation and therapeutic insights.","authors":"Ludmila Müller, Svetlana Di Benedetto","doi":"10.3389/fncel.2025.1590002","DOIUrl":"10.3389/fncel.2025.1590002","url":null,"abstract":"<p><p>The central nervous system (CNS) and the immune system are profoundly interconnected, engaging in a continuous dynamic exchange that regulates homeostasis, immune surveillance, and responses to injury. These interactions occur through diverse mechanisms, ranging from microglial activation and cytokine signaling to peripheral immune cell infiltration. When disrupted, this balance contributes to neurodegenerative processes, affecting cognitive function and neuronal survival. This mini-review examines the cellular and molecular foundations of neuroimmune communication, focusing on how neuroimmune interactions influence the onset and progression of neurodegenerative disorders such as Alzheimer's disease. Key mechanisms include barrier systems, gut-brain interactions, and circadian rhythm regulation, all playing a crucial role in modulating neuroinflammatory responses. The gut-brain axis plays a pivotal role in modulating CNS function, as alterations in gut microbiota composition can trigger neuroinflammatory pathways, affect systemic immunity, and influence disease susceptibility. Both innate and adaptive immune responses are instrumental in shaping disease trajectory, highlighting the complex interplay between systemic and neural immune components. The blood-brain barrier and glymphatic system modulate immune cell trafficking and waste clearance, influencing CNS pathology. Additionally, circadian rhythm and sleep patterns regulate neuroimmune balance, with disruptions exacerbating inflammation and neurodegeneration. Neuroimmune crosstalk manifests through a spectrum of pathways, each capable of either promoting resilience or accelerating neurodegeneration. By unraveling these connections, we can gain new insights into potential strategies to modulate immune responses and restore homeostasis. This investigation underlines the necessity of integrative approaches that target immune modulation, microbiota regulation, and circadian alignment to mitigate neurodegenerative disease progression and improve therapeutic outcomes.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1590002"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: The legacy of Sherrington and Adrian Nobel Prize: non-neuronal cells in information processing.","authors":"Wuhyun Koh, Zhuofan Lei","doi":"10.3389/fncel.2025.1634743","DOIUrl":"10.3389/fncel.2025.1634743","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1634743"},"PeriodicalIF":4.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Non-neuronal cells in neurodegenerative diseases and psychiatric disorders.","authors":"Enrique Estudillo, Gilberto Pérez-Sánchez, Lenin Pavón, Adriana Jiménez","doi":"10.3389/fncel.2025.1623523","DOIUrl":"https://doi.org/10.3389/fncel.2025.1623523","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1623523"},"PeriodicalIF":4.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics and machine learning identify iron metabolism genes MAP4, GPT, and HIRIP3 as diagnostic biomarkers and therapeutic targets in Alzheimer's disease.","authors":"Xiaoqiong An, Xiangguang Zeng, Zhenzhen Yi, Manni Cao, Yijia Wang, Wenfeng Yu, Zhenkui Ren","doi":"10.3389/fncel.2025.1610682","DOIUrl":"10.3389/fncel.2025.1610682","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and the accumulation of pathological markers such as amyloid-beta plaques and neurofibrillary tangles. Recent evidence suggests a role for dysregulated iron metabolism in the pathogenesis of AD, although the precise molecular mechanisms remain largely undefined.</p><p><strong>Materials and methods: </strong>To address the role of iron metabolism in AD, we utilized an integrative bioinformatics approach that combines weighted gene co-expression network analysis (WGCNA) with machine learning techniques, including LASSO regression and Generalized Linear Models (GLM), to identify hub genes associated with AD. We used transcriptomic data derived from postmortem prefrontal cortex samples (GSE132903, comprising 97 AD cases and 98 controls). To assess changes in the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was employed. Furthermore, pathway enrichment analysis and gene set variation analysis (GSVA) were performed to uncover the underlying biological mechanisms driving these alterations. Protein validation was carried out in APP/PS1 transgenic mice through Western blotting.</p><p><strong>Results: </strong>Three genes related to iron metabolism-MAP4, GPT, and HIRIP3-are identified as strong biomarkers. The GLM classifier showed high diagnostic accuracy (AUC=0.879). AD samples had increased immune activity, with more M1 macrophages and neutrophils, indicating neuroinflammation. MAP4 and GPT were linked to Notch signaling and metabolic issues. In APP/PS1 mice, MAP4 decreased, while GPT and HIRIP3 increased.</p><p><strong>Discussion: </strong>This analysis highlights these genes as diagnostic biomarkers and therapeutic targets, connecting iron balance, neuroinflammation, and metabolic problems in AD. The immune profile suggests potential for immunomodulatory treatments, enhancing understanding of AD and aiding precision diagnostics and therapies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1610682"},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sculptors of cerebellar fissures and their potential as therapeutic targets for cerebellar dysfunction.","authors":"Chiu-Lun Shen, Yu-Young Tsai, Woan-Yuh Tarn","doi":"10.3389/fncel.2025.1608185","DOIUrl":"10.3389/fncel.2025.1608185","url":null,"abstract":"<p><p>The cerebellum plays an important role in both motor control and cognition. The cerebellar cortex is neuron-rich and composed of characteristic folia and fissures. Defective cerebellar development leads to movement disorders and developmental delay. During early morphogenesis, cellular signaling programs orchestrate simultaneous cerebellar growth and foliation. Aberrant signaling causes various degrees of cerebellar hypoplasia. Based on mouse genetic studies, we discuss several developmental signaling pathways that drive cerebellar morphogenesis. Notably, hypoplasia of vermal lobules VI-VII has been linked to autism spectrum disorder and is in part attributed to brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B signaling. This review also discusses how BDNF biogenesis is critical for cerebellar foliation and whether restoring BDNF signaling could reverse cerebellar developmental disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1608185"},"PeriodicalIF":4.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of chronic alcohol consumption on cerebral ischemia/reperfusion injury in female mice.","authors":"Utsab Subedi, Pushpa Subedi, Asia Rogers, Xiao-Hong Lu, Manikandan Panchatcharam, Hong Sun","doi":"10.3389/fncel.2025.1600725","DOIUrl":"10.3389/fncel.2025.1600725","url":null,"abstract":"<p><p>Light alcohol consumption (LAC) protects against cerebral ischemia/reperfusion (I/R) injury, whereas heavy alcohol consumption (HAC) worsens it in male mice. The phenomenon appeared to be associated with the dose-dependent influence of alcohol on cerebral angiogenesis and post-ischemic inflammation. However, whether there is a sex-specific difference is unknown. Therefore, the goal of this study was to examine the influence of chronic alcohol consumption on cerebral I/R injury in female mice. Female C57BL/6J mice were gavage-fed with 0.7 g/kg/day ethanol (designed as LAC), 2.8 g/kg/day ethanol (designed as HAC), or volume-matched water (designed as control) for 8 weeks. Subsequently, they were subjected to unilateral middle cerebral artery occlusion (MCAO) for 60 min. Under basal conditions, LAC reduced erythrocytes, whereas HAC reduced lymphocytes and monocytes. Neither LAC nor HAC affected exploratory behavior and memory performance, but both improved spontaneous motor activity and reduced anxiety. In addition, both LAC and HAC upregulated VEGFR2 and promoted cerebral angiogenesis. Furthermore, LAC upregulated TGF-β and TGF-βR2 and HAC upregulated VEGF-A. Following MCAO, LAC significantly reduced cerebral I/R injury, blood-brain barrier (BBB) disruption, neutrophil infiltration, and microglial activation and increased cerebral angiogenesis at 72 h of reperfusion. In contrast, although HAC reduced BBB disruption and neutrophil infiltration, it did not significantly alter cerebral I/R injury, post-ischemic cerebral angiogenesis, or microglial activation. Our findings suggest that LAC protects against transient focal cerebral ischemia in female mice. The beneficial effect may be related to its pro-angiogenic and anti-inflammatory properties.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1600725"},"PeriodicalIF":4.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 actin mutants with neurodegenerative disease-like phenotypes via mutagenesis of the actin-ATP interface.","authors":"Noah Mann, Keerthana Surabhi, Josephine Sharp, Mary Phipps, Maelee Becton, Jahiem Hill, Davis Roberts, Erzsebet M Szatmari, Robert M Hughes","doi":"10.3389/fncel.2025.1543199","DOIUrl":"10.3389/fncel.2025.1543199","url":null,"abstract":"<p><p>Cofilin-actin rods are a well-documented stress response in neuronal cells and their persistence is frequently associated with neurodegenerative disease. However, the role of specific actin residues in promoting the formation of cofilin-actin rods and other anomalous cytoskeletal structures is largely unknown. As it is increasingly suspected that specific mutations and post-translation modifications of actin may promote neurodegenerative disease, characterizing the role of these residues in cytoskeletal dysregulation is highly relevant. In this study, we focus on the actin-ATP interface, which has been proposed as a key mediator of cofilin-actin rod formation and the propensity of actin to respond to cellular stress. Using a light and stress-gated reporter of cofilin-actin cluster formation, we determine the impact of mutants associated with Actin-ATP binding on the propensity of actin to form anomalous structures in the presence and absence of applied cellular stress. This study identifies actin mutants that promote anomalous actin inclusions in HeLa cells and characterizes the manifestation of these phenotypes in cortical neurons. Mutations to the ATP phosphate tail-binding region of actin (K18A, D154A, G158L, K213A) were found to be particularly disruptive to actin phenotypes, and in several instances promote disease-associated actin-rich structures such as cofilin-actin rods and Hirano bodies. We find that these mutant phenotypes are largely consistent between cell types and display highly unusual inclusions in cultured cortical neurons, without leading to nuclear fragmentation and apoptotic death of the transfected cells. These mutants strengthen the association of residue-specific changes in actin with large-scale phenotypic and functional changes in the cytoskeleton, further implicating them in neurodegenerative disease progression.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1543199"},"PeriodicalIF":4.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of juvenile social isolation on excitability of prefrontal pyramidal cells with different subcortical axonal projections.","authors":"Yosuke Nishihata, Hiroki Yoshino, Yoichi Ogawa, Taketoshi Sugimura, Kazuya Okamura, Sohei Kimoto, Kazuhiko Yamamuro, Manabu Makinodan, Yasuhiko Saito, Toshifumi Kishimoto","doi":"10.3389/fncel.2025.1549352","DOIUrl":"10.3389/fncel.2025.1549352","url":null,"abstract":"<p><strong>Background: </strong>Social experience during development is crucial for the functional maturation of the prefrontal cortex (PFC). Juvenile social isolation (JSI) causes severe PFC dysfunction. JSI reduces intrinsic excitability and excitatory synaptic inputs for a subtype of layer-5 (L5) pyramidal cells showing prominent h-current (PH cells) in the medial PFC. PH cells do not have commissural or associational cortical output; instead, they project into subcortical areas. However, which subcortical area is the projection target of L5 pyramidal cells affected by JSI remains unascertained.</p><p><strong>Methods: </strong>Using retrograde neuronal tracing, we identified L5 pyramidal cells having three different projection targets: the mediodorsal thalamus, striatum, or pontine nuclei. We elucidated differences in functional properties among the three subclasses of L5 pyramidal cells and examined how JSI affects the intrinsic membrane properties and excitatory inputs for each class of L5 pyramidal cells.</p><p><strong>Results: </strong>Pyramidal cells projecting to the pontine nuclei had more excitatory synaptic inputs and more distinguishing intrinsic properties than pyramidal cells projecting to the mediodorsal thalamus and striatum. JSI increased the firing responsiveness of pyramidal cell projecting to mediodorsal thalamus and reduced excitatory synaptic inputs only onto pyramidal cells projecting to the pontine nuclei.</p><p><strong>Conclusion: </strong>JSI affects the development of L5 pyramidal cells based on their projection target.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1549352"},"PeriodicalIF":4.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the use of cuprizone and lysolecithin to model demyelination <i>ex vivo</i> in sagittal rat brain organotypic slice cultures.","authors":"Brooke Hawker, Bronwen Connor, Amy McCaughey-Chapman","doi":"10.3389/fncel.2025.1609806","DOIUrl":"10.3389/fncel.2025.1609806","url":null,"abstract":"<p><strong>Introduction: </strong>The development of organotypic slice cultures of central nervous system (CNS) tissues has bridged the gap between simple in vitro cell cultures and complex in vivo whole animal studies. Organotypic brain slice cultures are a useful tool to study neurological disease, providing a more complex 3-dimensional system than standard 2-dimensional in vitro cell culture. In particular, organotypic brain slice cultures provide an excellent model to study the processes of demyelination and remyelination associated with neurological disease and injury. However, organotypic brain slice cultures are typically generated using coronal sectioning or regionspecific hippocampal or cerebellar tissue. We have previously reported the ability to generate sagittal organotypic brain slice cultures, allowing us to investigate the anterior-to-posterior integrity of the corpus callosum during demyelination and remyelination processes. To extend our sagittal organotypic brain slice culture model, this study compares the ability for two common demyelinating agents, cuprizone (CPZ) or lysolecithin (LPC), to induce demyelination of the corpus callosum.</p><p><strong>Methods: </strong>Rat brain sagittal organotypic slice cultures were generated with clear visualization of the corpus callosum and treated either with CPZ (1 mM) or LPC (0.5 mg/mL).</p><p><strong>Results: </strong>We demonstrate that CPZ treatment induces acute demyelination followed by endogenous remyelination 1-week post-treatment. Conversely, we show that LPC treatment results in prolonged demyelination of the corpus callosum that is maintained 5 weeks post-treatment and is associated with an acute astroglia response.</p><p><strong>Discussion: </strong>Overall, this study demonstrates the use of CPZ and LPC to model either acute or prolonged demyelination in a sagittal organotypic brain slice culture system. These models provide a platform for studying acute and chronic demyelination and for testing new therapeutic approaches aimed at enhancing remyelination prior to conducting in vivo experiments.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1609806"},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}