Frontiers in Cellular Neuroscience最新文献

{"title":"Interplay between noise-induced sensorineural hearing loss and hypertension: pathophysiological mechanisms and therapeutic prospects.","authors":"Carola Y Förster, Sergey Shityakov, Stavros Stavrakis, Verena Scheper, Thomas Lenarz","doi":"10.3389/fncel.2025.1523149","DOIUrl":"https://doi.org/10.3389/fncel.2025.1523149","url":null,"abstract":"<p><p>More than 5% of the global population suffers from disabling hearing loss, primarily sensorineural hearing loss (SNHL). SNHL is often caused by factors such as vascular disorders, viral infections, ototoxic drugs, systemic inflammation, age-related labyrinthine membrane degeneration, and noise-induced hearing loss (NIHL). NIHL, in particular, leads to changes in blood-labyrinth-barrier (BLB) physiology, increased permeability, and various health issues, including cardiovascular disease, hypertension, diabetes, neurological disorders, and adverse reproductive outcomes. Recent advances in neuromodulation and vector-based approaches offer hope for overcoming biological barriers such as the BLB in the development of innovative treatments. Computational methods, including molecular docking, molecular dynamics simulations, QSAR/QSPR analysis with machine/deep learning algorithms, and network pharmacology, hold potential for identifying drug candidates and optimizing their interactions with BLB transporters, such as the glutamate transporter. This paper provides an overview of NIHL, focusing on its pathophysiology; its impact on membrane transporters, ion channels, and BLB structures; and associated symptoms, comorbidities, and emerging therapeutic approaches. Recent advancements in neuromodulation and vector-based strategies show great promise in overcoming biological barriers such as BLB, facilitating the development of innovative treatment options. The primary aim of this review is to examine NIHL in detail and explore its underlying mechanisms, physiological effects, and cutting-edge therapeutic strategies for its effective management and prevention.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1523149"},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062653","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":"CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.","authors":"Mohamad Sultan Khan, Nousheen Qureshi, Rehan Khan, Young-Ok Son, Tariq Maqbool","doi":"10.3389/fncel.2025.1578138","DOIUrl":"https://doi.org/10.3389/fncel.2025.1578138","url":null,"abstract":"<p><p>CRISPR/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing and modulation of gene function with an unparalleled precision and effectiveness. Among the various applications and prospects of this technology, the opportunities it offers in unraveling the molecular underpinnings of a myriad of central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, and developmental abnormalities, are unprecedented. In this review, we highlight the applications of CRISPR/Cas9-based therapeutics as a promising strategy for management of Alzheimer's disease and transformative impact of this technology on AD research. Further, we emphasize the role of CRISPR/Cas9 in generating accurate AD models for identification of novel therapeutic targets, besides the role of CRISPR-based therapies aimed at correcting AD-associated mutations and modulating the neurodegenerative processes. Furthermore, various delivery systems are reviewed and potential of the non-viral nanotechnology-based carriers for overcoming the critical limitations of effective delivery systems for CRISPR/Cas9 is discussed. Overall, this review highlights the promise and prospects of CRISPR/Cas9 technology for unraveling the intricate molecular processes underlying the development of AD, discusses its limitations, ethical concerns and several challenges including efficient delivery across the BBB, ensuring specificity, avoiding off-target effects. This article can be helpful in better understanding the applications of CRISPR/Cas9 based therapeutic approaches and the way forward utilizing enormous potential of this technology in targeted, gene-specific treatments that could change the trajectory of this debilitating and incurable illness.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1578138"},"PeriodicalIF":4.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977818","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":"Natural killer cells in multiple sclerosis: foe or friends?","authors":"Fatemeh Aghaee, Mohammadreza Abedinpour, Saeid Anvari, Alia Saberi, Amir Fallah, Arash Bakhshi","doi":"10.3389/fncel.2025.1500770","DOIUrl":"https://doi.org/10.3389/fncel.2025.1500770","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an immune-mediated disorder involving the central nervous system (CNS), in which demyelination is caused. The initiation and progression of MS is thought to depend largely on CD4⁺ T lymphocytes, yet new data has emphasized the involvement of the innate immune system in the MS disease responses. Generally, several types of immune cells play a part, with natural killer (NK) cells being essential. Different subsets of natural killer cells function differently within the course of an autoimmune disease, such as MS. There are mainly two types of natural killers in humans: immature CD56 ^{<i>bright</i>} CD16^- and mature CD56 ^<i>dim</i> CD16⁺ natural killers, together with their respective subtypes. Factors from natural killers expand the T cell population and control the process by which native CD4⁺ T cells differentiate into Th1 or Th2 lymphocytes, which affect autoimmune responses. Natural killer subsets CD56 ^{<i>bright</i>} and CD56 ^<i>dim</i> may have differing roles in MS development. The impact of these NK cell subsets is influenced by factors such as Granzymes, genetics, infections, TLR, and HSP. We reviewed and evaluated the relationship between natural killer cells and MS.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1500770"},"PeriodicalIF":4.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961812","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":"An electrophysiologist's guide to dorsal horn excitability and pain.","authors":"Iván Rivera-Arconada, Mark L Baccei, José A López-García, Rita Bardoni","doi":"10.3389/fncel.2025.1548252","DOIUrl":"https://doi.org/10.3389/fncel.2025.1548252","url":null,"abstract":"<p><p>The dorsal horn of the spinal cord represents the first site in the central nervous system (CNS) where nociceptive signals are integrated. As a result, there has been a rapid growth in the number of studies investigating the ionic mechanisms regulating the excitability of dorsal horn neurons under normal and pathological conditions. We believe that it is time to look back and to critically examine what picture emerges from this wealth of studies. What are the actual types of neurons described in the literature based on electrophysiological criteria? Are these electrophysiologically-defined subpopulations strongly linked to specific morphological, functional, or molecular traits? Are these electrophysiological properties stable, or can they change during development or in response to peripheral injury? Here we provide an in-depth overview of both early and recent publications that explore the factors influencing dorsal horn neuronal excitability (including intrinsic membrane properties and synaptic transmission), how these factors vary across distinct subtypes of dorsal horn neurons, and how such factors are altered by peripheral nerve or tissue damage. The meta-research presented below leads to the conclusion that the dorsal horn is comprised of highly heterogeneous subpopulations in which the observed electrophysiological properties of a given neuron often fail to easily predict other properties such as biochemical phenotype or morphology. This highlights the need for future studies which can more fully interrogate the properties of dorsal horn neurons in a multi-modal manner.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1548252"},"PeriodicalIF":4.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995513","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":"Combined strategy of α 9-integrin transduction and AEIDGIEL peptide-functionalized fibrin gel biomaterials to promote mature DRG neurite growth.","authors":"Anda Cimpean, Lars Roll, Jacqueline Reinhard, Jessica C F Kwok, Andreas Faissner, Fred de Winter, James W Fawcett, Pavla Jendelová","doi":"10.3389/fncel.2025.1568004","DOIUrl":"https://doi.org/10.3389/fncel.2025.1568004","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord injury involves complex pathobiological mechanisms, necessitating a multidimensional approach for its cure. Previous studies have shown that α9-integrin expression and activation in mature dorsal root ganglion neurons enable the regeneration of injured axons within the spinal cord. However, tissue cavitation and fibrosis impede the regenerating axons from following their usual pathways, forcing them to seek alternative routes rich in tenascin-C, the primary ligand of the integrin. Fibrin gel, an FDA-approved and biocompatible material, can offer three-dimensional support for axonal extension through the cavitated area, thus preventing the formation of aberrant paths and connections that occur in the absence of a suitable scaffold.</p><p><strong>Methods: </strong>The aim of this study was to investigate how combining α9-integrin expression by adeno-associated virus with the use of a fibrin gel as an extracellular microenvironment affects the growth of mature DRG neurites <i>in vitro</i>. Additionally, we sought to functionalize fibrin with integrin ligand peptides, specifically AEIDGIEL, the active domain of tenascin-C, to ensure α9-integrin activation.</p><p><strong>Results: </strong>Our results indicate that fibrin gels are a suitable biomaterial for promoting neurite growth and that AEIDGIEL peptide effectively activates the integrin. Furthermore, we corroborate an autocrine signaling loop of α9-integrin and TN-C produced by neurons.</p><p><strong>Discussion: </strong>the proposed combination therapy of α9-integrin and fibrin gel biomaterials incorporating AEIDGIEL peptide shows promise for addressing the complex challenges of spinal cord injury and promoting effective neural regeneration, laying the foundation for further <i>in vivo</i> research.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1568004"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996270","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: Metabolic dysregulation in neurodegenerative diseases.","authors":"Maria Jimenez-Gonzalez","doi":"10.3389/fncel.2025.1591313","DOIUrl":"https://doi.org/10.3389/fncel.2025.1591313","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1591313"},"PeriodicalIF":4.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983572","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":"Corrigendum: Hypidone hydrochloride (YL-0919) produces a fast-onset reversal of the behavioral and synaptic deficits caused by chronic stress exposure.","authors":"Yuhua Ran, Zengliang Jin, Xiaofei Chen, Nan Zhao, Xinxin Fang, Liming Zhang, Youzhi Zhang, Yunfeng Li","doi":"10.3389/fncel.2025.1558690","DOIUrl":"https://doi.org/10.3389/fncel.2025.1558690","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2018.00395.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1558690"},"PeriodicalIF":4.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972432","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":"Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms.","authors":"Ya Liu, Xiao-Qian Wang, Peng Zhang, Abbas Haghparast, Wen-Bin He, Jian-Jun Zhang","doi":"10.3389/fncel.2025.1566001","DOIUrl":"https://doi.org/10.3389/fncel.2025.1566001","url":null,"abstract":"<p><p>Drug abuse can damage the central nervous system and lead to substance use disorder (SUD). SUD is influenced by both genetic and environmental factors. Genes determine an individual's susceptibility to drug, while the dysregulation of epigenome drives the abnormal transcription processes, promoting the development of SUD. One of the most widely studied epigenetic mechanisms is DNA methylation, which can be inherited stably. In ontogeny, DNA methylation pattern is dynamic. DNA dysmethylation is prevalent in drug-related psychiatric disorders, resulting in local hypermethylation and transcriptional silencing of related genes. In this review, we summarize the role and regulatory mechanisms of DNA methylation in cocaine, opioids, and methamphetamine in terms of drug exposure, addiction memory, withdrawal relapse, intergenerational inheritance, and focus on cell-specific aspects of the studies with a view to suggesting possible therapeutic regimens for targeting methylation in both human and animal research.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1566001"},"PeriodicalIF":4.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999581","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":"A vascular endothelial cell, neuron, and microglia tri-culture model to study hypertension-related depression.","authors":"Hongxia Zhao, Lingge Huang, Jian Liu, Min Feng, Yeqian Liu, Hong Li, Shan Gong, Chunming Chen, Shuiqing Zeng, Weiqiong Ren","doi":"10.3389/fncel.2025.1553309","DOIUrl":"https://doi.org/10.3389/fncel.2025.1553309","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Hypertension-related Depression (HD) is a complex mental disorder that exerts a significant negative impact on patients' quality of life. Previous studies have demonstrated that damages to vascular endothelial and hippocampus are the primary pathological features in HD rats. Under hypertensive conditions, inflammatory cytokines in peripheral blood vessels can induce central nervous system inflammation through penetration of a damaged blood-brain barrier, peripheral immune cells, and neural pathways, damaging the brain and triggering HD. Therefore, interactions between vascular endothelial cells, neurons, and glial cells are critical for the understanding of HD. However, &lt;i&gt;in vivo&lt;/i&gt; animal models are often limited by the complexity of intrinsic systems, high inter-individual variability, and stringent ethical regulations. A reliable model that could be easily manipulated is needed for investigating the mechanisms involved in communication between vascular endothelial cells, neurons, and glial cells in HD. We therefore aimed to create a composite tri-culture model consisting of rat aortic endothelial cells (RAECs), neurons, and microglia to study HD. First, RAECs were stimulated with lipopolysaccharide to mimic endothelial injury under hypertensive conditions. Vascular endothelial function and inflammatory levels were assessed using fluorescent probes and enzyme-linked immunosorbent assays. RAECs treated with 1 μg/ml LPS for 24 h had reduced levels of nitric oxide, increased levels of endothelin-1 and inflammatory mediators. These findings are consistent with the endothelial dysfunction and inflammatory responses observed in spontaneously hypertensive rats, which suggests that the lipopolysaccharide-induced RAECs model effectively mimics key pathological features of hypertension-related endothelial injury. Subsequently, the supernatants from lipopolysaccharide-induced RAECs were combined with 200 μM corticosterone and transferred to neuron-microglia co-cultures to simulate damages to hippocampal neuron under HD conditions. To evaluate the features of cells, neuronal viability was measured by CCK-8 and live-dead assays. Nissl staining was used to assess neuronal Nissl bodies, while the levels of inflammatory factors and monoamine neurotransmitters in the culture supernatants were evaluated by enzyme-linked immunosorbent assays. Reactive oxygen species in neurons were visualized by a fluorescent probe, apoptosis was detected using TUNEL assays, and immunofluorescence was used to assess microglial phenotypes and the levels of TLR4 and NF-κB. It was found that neurons in the tri-culture model had reduced viability, higher levels of apoptosis, fewer Nissl bodies, increased inflammation, and reduced levels of monoamine neurotransmitters. Additionally, the number of M1 microglia was increased, along with elevated levels of TLR4 and NF-κB proteins. These findings were similar to damages of hippocampal neuron, abnormal levels of monoamine neurotran","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1553309"},"PeriodicalIF":4.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062634","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":"Ca²⁺ waves in astrocytes: computational modeling and experimental data.","authors":"Rosa Musotto, Ulderico Wanderlingh, Giovanni Pioggia","doi":"10.3389/fncel.2025.1536096","DOIUrl":"https://doi.org/10.3389/fncel.2025.1536096","url":null,"abstract":"<p><p>This paper examines different computational models for Calcium wave propagation in astrocytes. Through a comparative analysis of models by Goldbeter, De Young-Keizer, Atri, Li-Rinzel, and De Pittà and of experimental data, the study highlights the model contributions for the understanding of Calcium dynamics. Tracing the evolution from simple to complex models, this work emphasizes the importance of integrating experimental data in order to further refine these models. The results allow to improve our understanding of the physiological functions of astrocytes, suggesting the importance of more accurate astrocyte models.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1536096"},"PeriodicalIF":4.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975981","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}