Frontiers in Cellular Neuroscience最新文献

{"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}

{"title":"Role of mitochondrial quality control in neurodegenerative disease progression.","authors":"Tingting Liu, Weibo Sun, Shuhao Guo, Zhiying Yuan, Minghang Zhu, Jing Lu, Tao Chen, Yuanyuan Qu, Chuwen Feng, Tiansong Yang","doi":"10.3389/fncel.2025.1588645","DOIUrl":"10.3389/fncel.2025.1588645","url":null,"abstract":"<p><p>Neurodegenerative diseases are a diverse group of neurological disorders, in which abnormal mitochondrial function is closely associated with their development and progression. This has generated significant research interest in the field. The proper functioning of mitochondria relies on the dynamic regulation of the mitochondrial quality control system. Key processes such as mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (division/fusion) are essential for maintaining this balance. These processes collectively govern mitochondrial function and homeostasis. Therefore, the mitochondrial quality control system plays a critical role in the onset and progression of neurodegenerative diseases. This article provides a concise overview of the molecular mechanisms involved in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics, explores their interactions, and summarizes current research progress in understanding the mitochondrial quality control system in the context of neurodegenerative diseases.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1588645"},"PeriodicalIF":4.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215414","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":"Cellular and synaptic specializations for sub-millisecond precision in the mammalian auditory brainstem.","authors":"Christian Keine, Bernhard Englitz","doi":"10.3389/fncel.2025.1568506","DOIUrl":"10.3389/fncel.2025.1568506","url":null,"abstract":"<p><p>Audition in all animals relies on delicate sound pressure variations arriving at the ears, and these sound waves are intertwined representations of the complex auditory environment. The process of auditory perception and behavior is fundamentally based on reconstructive analysis, starting at the auditory nerve and culminating in the segregation of auditory sources through the extraction of spatial, spectral, and temporal cues. This analysis is made possible by specialized structures in the auditory brainstem that accurately represent and process incoming signals, preparing them for various downstream analyses. Decades of research have provided substantial insight into the morphological and physiological adaptations of specific auditory synapses, which we present and compare in the context of their presumed functions. Here, we focus on two parallel pathways originating from the auditory nerve and converging in the midbrain, featuring several well-studied synapses across multiple nuclei (cochlear nucleus, medial nucleus of the trapezoid body, ventral nucleus of the lateral lemniscus, and medial and lateral superior olivary nuclei). These synapses form the backbone of the high temporal precision of auditory representation, which is crucial for sound localization, speech comprehension, and speaker identification, each relying on subtle monaural or binaural cues. Finally, we highlight the similarities and differences with other brain areas that face challenges comparable to those of the auditory system.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1568506"},"PeriodicalIF":4.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208147","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":"Astrocyte regulation of behavioral outputs: the versatile roles of calcium.","authors":"Gillian Imrie, Isabella Farhy-Tselnicker","doi":"10.3389/fncel.2025.1606265","DOIUrl":"10.3389/fncel.2025.1606265","url":null,"abstract":"<p><p>Behavior arises from coordinated brain-wide neural and glial networks, enabling organisms to perceive, interpret, and respond to stimuli. Astrocytes play an important role in shaping behavioral output, yet the underlying molecular mechanisms are not fully understood. Astrocytes respond to intrinsic and extrinsic cues with calcium (Ca²⁺) fluctuations, which are highly heterogeneous across spatio-temporal scales, contexts, and brain regions. This heterogeneity allows astrocytes to exert dynamic regulatory effects on neuronal function but has made it challenging to understand the precise mechanisms and pathways linking astrocytic Ca²⁺ to specific behavioral outcomes, and the functional relevance of these signals remains unclear. Here, we review recent literature uncovering roles for astrocytic Ca²⁺ signaling in a wide array of behaviors, including cognitive, homeostatic, and affective focusing on its physiological roles, and potential pathological implications. We specifically highlight how different types of astrocytic Ca²⁺ signals are linked to distinct behavioral outcomes and discuss limitations and unanswered questions that remain to be addressed.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1606265"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181488","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}