Frontiers in Cellular Neuroscience最新文献

{"title":"Genetic approaches to elucidating cortical and hippocampal GABAergic interneuron diversity","authors":"Robert Machold, Bernardo Rudy","doi":"10.3389/fncel.2024.1414955","DOIUrl":"https://doi.org/10.3389/fncel.2024.1414955","url":null,"abstract":"GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms of local inhibition to regulate neural circuit activity. Over the last few decades, the development of a palette of genetic tools along with the generation of single-cell transcriptomic data has begun to reveal the molecular basis of IN diversity, thereby providing deep insights into how different IN subtypes function in the forebrain. In this review, we outline the emerging picture of cortical and hippocampal IN speciation as defined by transcriptomics and developmental origin and summarize the genetic strategies that have been utilized to target specific IN subtypes, along with the technical considerations inherent to each approach. Collectively, these methods have greatly facilitated our understanding of how IN subtypes regulate forebrain circuitry via cell type and compartment-specific inhibition and thus have illuminated a path toward potential therapeutic interventions for a variety of neurocognitive disorders.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendrocyte precursor cell-derived exosomes combined with cell therapy promote clinical recovery by immunomodulation and gliosis attenuation","authors":"Sarah Ingrid Pinto Santos, Santiago José Ortiz-Peñuela, Alessandro de Paula Filho, Ana Laura Midori Rossi Tomiyama, Lilian de Oliveira Coser, Juliano Coelho da Silveira, Daniele dos Santos Martins, Adriano Polican Ciena, Alexandre Leite Rodrigues de Oliveira, Carlos Eduardo Ambrósio","doi":"10.3389/fncel.2024.1413843","DOIUrl":"https://doi.org/10.3389/fncel.2024.1413843","url":null,"abstract":"Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by autoimmune destruction of the myelin sheath, leading to irreversible and progressive functional deficits in patients. Pre-clinical studies involving the use of neural stem cells (NSCs) have already demonstrated their potential in neuronal regeneration and remyelination. However, the exclusive application of cell therapy has not proved sufficient to achieve satisfactory therapeutic levels. Recognizing these limitations, there is a need to combine cell therapy with other adjuvant protocols. In this context, extracellular vesicles (EVs) can contribute to intercellular communication, stimulating the production of proteins and lipids associated with remyelination and providing trophic support to axons. This study aimed to evaluate the therapeutic efficacy of the combination of NSCs and EVs derived from oligodendrocyte precursor cells (OPCs) in an animal model of multiple sclerosis. OPCs were differentiated from NSCs and had their identity confirmed by gene expression analysis and immunocytochemistry. Exosomes were isolated by differential ultracentrifugation and characterized by Western, transmission electron microscopy and nanoparticle tracking analysis. Experimental therapy of C57BL/6 mice induced with experimental autoimmune encephalomyelitis (EAE) were grouped in control, treated with NSCs, treated with OPC-derived EVs and treated with a combination of both. The treatments were evaluated clinically using scores and body weight, microscopically using immunohistochemistry and immunological profile by flow cytometry. The animals showed significant clinical improvement and weight gain with the treatments. However, only the treatments involving EVs led to immune modulation, changing the profile from Th1 to Th2 lymphocytes. Fifteen days after treatment revealed a reduction in reactive microgliosis and astrogliosis in the groups treated with EVs. However, there was no reduction in demyelination. The results indicate the potential therapeutic use of OPC-derived EVs to attenuate inflammation and promote recovery in EAE, especially when combined with cell therapy.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel histone deacetylase inhibitor W2A-16 improves the barrier integrity in brain vascular endothelial cells","authors":"Yasuteru Inoue, Yingxue Ren, Shuwen Zhang, Michael Bamkole, Naeyma N. Islam, Manikandan Selvaraj, Wenyan Lu, Thomas R. Caulfield, Yonghe Li, Takahisa Kanekiyo","doi":"10.3389/fncel.2024.1368018","DOIUrl":"https://doi.org/10.3389/fncel.2024.1368018","url":null,"abstract":"The maturation of brain microvascular endothelial cells leads to the formation of a tightly sealed monolayer, known as the blood–brain barrier (BBB). The BBB damage is associated with the pathogenesis of age-related neurodegenerative diseases including vascular cognitive impairment and Alzheimer’s disease. Growing knowledge in the field of epigenetics can enhance the understanding of molecular profile of the BBB and has great potential for the development of novel therapeutic strategies or targets to repair a disrupted BBB. Histone deacetylases (HDACs) inhibitors are epigenetic regulators that can induce acetylation of histones and induce open chromatin conformation, promoting gene expression by enhancing the binding of DNA with transcription factors. We investigated how HDAC inhibition influences the barrier integrity using immortalized human endothelial cells (HCMEC/D3) and the human induced pluripotent stem cell (iPSC)-derived brain vascular endothelial cells. The endothelial cells were treated with or without a novel compound named W2A-16. W2A-16 not only activates Wnt/β-catenin signaling but also functions as a class I HDAC inhibitor. We demonstrated that the administration with W2A-16 sustained barrier properties of the monolayer of endothelial cells, as evidenced by increased trans-endothelial electrical resistance (TEER). The BBB-related genes and protein expression were also increased compared with non-treated controls. Analysis of transcript profiles through RNA-sequencing in hCMEC/D3 cells indicated that W2A-16 potentially enhances BBB integrity by influencing genes associated with the regulation of the extracellular microenvironment. These findings collectively propose that the HDAC inhibition by W2A-16 plays a facilitating role in the formation of the BBB. Pharmacological approaches to inhibit HDAC may be a potential therapeutic strategy to boost and/or restore BBB integrity.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABAA receptors and neuroligin 2 synergize to promote synaptic adhesion and inhibitory synaptogenesis","authors":"Yusheng Sui, Martin Mortensen, Banghao Yuan, Martin W. Nicholson, Trevor G. Smart, Jasmina N. Jovanovic","doi":"10.3389/fncel.2024.1423471","DOIUrl":"https://doi.org/10.3389/fncel.2024.1423471","url":null,"abstract":"GABA<jats:sub>A</jats:sub> receptors (γ-aminobutyric acid-gated receptors type A; GABA<jats:sub>A</jats:sub>Rs), the major structural and functional postsynaptic components of inhibitory synapses in the mammalian brain, belong to a family of GABA-gated Cl<jats:sup>−</jats:sup>/HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup> ion channels. They are assembled as heteropentamers from a family of subunits including: α (1–6), β(1–3), γ(1–3), δ, ε, π, θ and ρ(1–3). GABA<jats:sub>A</jats:sub>Rs together with the postsynaptic adhesion protein Neuroligin 2 (NL2) and many other pre- and post-synaptic proteins guide the initiation and functional maturation of inhibitory GABAergic synapses. This study examined how GABA<jats:sub>A</jats:sub>Rs and NL2 interact with each other to initiate the formation of synapses. Two functionally distinct GABA<jats:sub>A</jats:sub>R subtypes, the synaptic type α2β2γ2-GABA<jats:sub>A</jats:sub>Rs versus extrasynaptic type α4β3δ-GABA<jats:sub>A</jats:sub>Rs were expressed in HEK293 cells alone or together with NL2 and co-cultured with striatal GABAergic medium spiny neurons to enable innervation of HEK293 cells by GABAergic axons. When expressed alone, only the synaptic α2β2γ2-GABA<jats:sub>A</jats:sub>Rs induced innervation of HEK293 cells. However, when GABA<jats:sub>A</jats:sub>Rs were co-expressed with NL2, the effect on synapse formation exceeded the individual effects of these proteins indicating a synergistic interaction, with α2β2γ2-GABA<jats:sub>A</jats:sub>R/NL2 showing a significantly greater synaptogenic activity than α4β3δ-GABA<jats:sub>A</jats:sub>R/NL2 or NL2 alone. To investigate the molecular basis of this interaction, different combinations of GABA<jats:sub>A</jats:sub>R subunits and NL2 were co-expressed, and the degree of innervation and synaptic activity assessed, revealing a key role of the γ2 subunit. In biochemical assays, the interaction between NL2 and α2β2γ2-GABA<jats:sub>A</jats:sub>R was established and mapped to the large intracellular domain of the γ2 subunit.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological activity pattern of mouse hippocampal CA1 and dentate gyrus under isoflurane anesthesia","authors":"Rui Wang, Linzhong Zhang, Xia Wang, Wen Li, Tingliang Jian, Pengcheng Yin, Xinzhi Wang, Qianwei Chen, Xiaowei Chen, Han Qin","doi":"10.3389/fncel.2024.1392498","DOIUrl":"https://doi.org/10.3389/fncel.2024.1392498","url":null,"abstract":"General anesthesia can impact a patient’s memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial cells in the mammalian olfactory bulb","authors":"Dan Zhao, Meigeng Hu, Shaolin Liu","doi":"10.3389/fncel.2024.1426094","DOIUrl":"https://doi.org/10.3389/fncel.2024.1426094","url":null,"abstract":"The mammalian olfactory bulb (OB), an essential part of the olfactory system, plays a critical role in odor detection and neural processing. Historically, research has predominantly focused on the neuronal components of the OB, often overlooking the vital contributions of glial cells. Recent advancements, however, underscore the significant roles that glial cells play within this intricate neural structure. This review discus the diverse functions and dynamics of glial cells in the mammalian OB, mainly focused on astrocytes, microglia, oligodendrocytes, olfactory ensheathing cells, and radial glia cells. Each type of glial contributes uniquely to the OB's functionality, influencing everything from synaptic modulation and neuronal survival to immune defense and axonal guidance. The review features their roles in maintaining neural health, their involvement in neurodegenerative diseases, and their potential in therapeutic applications for neuroregeneration. By providing a comprehensive overview of glial cell types, their mechanisms, and interactions within the OB, this article aims to enhance our understanding of the olfactory system's complexity and the pivotal roles glial cells play in both health and disease.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers | Peptain-1 blocks ischemia/reperfusion-induced retinal capillary degeneration in mice","authors":"Mi-Hyun Nam, Armaan Dhillon, Rooban B. Nahomi, Noelle L. Carrillo, Clarinda S. Hougen, Ram H. Nagaraj","doi":"10.3389/fncel.2024.1441924","DOIUrl":"https://doi.org/10.3389/fncel.2024.1441924","url":null,"abstract":"IntroductionNeurovascular degeneration results in vascular dysfunction, leakage, ischemia, and structural changes that can lead to significant visual impairment. We previously showed the protective effects of peptain-1, a 20 amino acid peptide derived from the αB-crystallin core domain, on retinal ganglion cells in two animal models of glaucoma. Here, we evaluated the ability of peptain-1 to block apoptosis of human retinal endothelial cells (HRECs) in vitro and retinal capillary degeneration in mice subjected to retinal ischemia/reperfusion (I/R) injury.MethodsHRECs were treated with either peptain-1 or scrambled peptides (200 μg/mL) for 3 h and a combination of proinflammatory cytokines (IFN-γ 20 ng/mL + TNF-α 20 ng/mL+ IL-1β 20 ng/mL) for additional 48 h. Apoptosis was measured with cleaved caspase-3 formation via western blot, and by TUNEL assay. C57BL/6J mice (12 weeks old) were subjected to I/R injury by elevating the intraocular pressure to 120 mmHg for 60 min, followed by reperfusion. Peptain-1 or scrambled peptide (0.5 μg) was intravitreally injected immediately after I/R injury and 7 days later. One microliter of PBS was injected as vehicle control, and animals were euthanized on day 14 post-I/R injury. Retinal capillary degeneration was assessed after enzyme digestion followed by periodic acid–Schiff staining.ResultsOur data showed that peptain-1 entered HRECs and blocked proinflammatory cytokine-mediated apoptosis. Intravitreally administered peptain-1 was distributed throughout the retinal vessels after 4 h. I/R injury caused retinal capillary degeneration. Unlike scrambled peptide, peptain-1 protected capillaries against I/R injury. Additionally, peptain-1 inhibited microglial activation and reduced proinflammatory cytokine levels in the retina following I/R injury.DiscussionOur study suggests that peptain-1 could be used as a therapeutic agent to prevent capillary degeneration and neuroinflammation in retinal ischemia.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141869046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of corneal nerve regeneration after axotomy in a compartmentalized microfluidic chip model with automated 3D high resolution live-imaging","authors":"N. Bonneau, A. Potey, Frédéric Blond, Camille Guerin, C. Baudouin, J. Peyrin, F. Brignole-Baudouin, A. Réaux-Le Goazigo","doi":"10.3389/fncel.2024.1417653","DOIUrl":"https://doi.org/10.3389/fncel.2024.1417653","url":null,"abstract":"Damage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings.To overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live–imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy.Physical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72 h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72 h of exposure (versus 34% regrowth without any compound).Combining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Space and neural cell: the impact of space environment on neurological function and their molecular mechanistic insights","authors":"Zixuan Chen, Zongjian Liu, Di Wu, Yulin Deng","doi":"10.3389/fncel.2024.1454014","DOIUrl":"https://doi.org/10.3389/fncel.2024.1454014","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia as potential key regulators in viral-induced neuroinflammation","authors":"F. Ismail, Timo Jendrik Faustmann, P. Faustmann, Franco Corvace","doi":"10.3389/fncel.2024.1426079","DOIUrl":"https://doi.org/10.3389/fncel.2024.1426079","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}