Frontiers in Cellular Neuroscience最新文献

{"title":"Editorial: Human brain organoids to model neurodegenerative diseases at the BOSS23 Brain Organoid Summer School.","authors":"Fabio Cavaliere, Dirk M Hermann, Chiara Magliaro","doi":"10.3389/fncel.2024.1501036","DOIUrl":"https://doi.org/10.3389/fncel.2024.1501036","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1501036"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675297","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":"The emerging role of disease-associated microglia in Parkinson's disease.","authors":"Ritika R Samant, David G Standaert, Ashley S Harms","doi":"10.3389/fncel.2024.1476461","DOIUrl":"10.3389/fncel.2024.1476461","url":null,"abstract":"<p><p>Disease-associated microglia (DAM) are a subset of microglia that appear at various stages of central nervous system neurodegenerative diseases. DAM were identified using single-cell RNA sequencing within Alzheimer's Disease (AD) where they were characterized by their unique localization near amyloid-β plaques and their phagocytic and lipid-metabolizing features. Unfortunately, activation and etiology of DAM are only understood within the context of AD where Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), a receptor for amyloid-β, appears to be the key regulator in microglial transition to a DAM state. Despite this reliance on TREM2 in AD, DAM appear across other neurodegenerative diseases in which TREM2 may not be a critical player. This begs the question of if DAM are truly the same across all neurodegenerative diseases or if there exists a heterogeneity to DAM across neurodegenerative pathologies. Investigation into this critical gap in the field regarding DAM etiology and activation, as well as DAM function, could be delineated utilizing models of Parkinson's disease (PD) to complement studies in models of AD. Though highly underexplored regarding DAM, PD with its pattern of protein aggregation-associated pathology like AD could serve as the spatiotemporal comparison against AD findings to ascertain the nature of DAM. The experimental vehicle that could guide the future of such investigation is the multi-omics model. With a compound approach focusing on exploring triggers for DAM at the chromatin or mRNA level and related protein output, it becomes possible to strongly characterize and firmly answer the question of what is a DAM.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1476461"},"PeriodicalIF":4.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675224","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":"Magnetic field in the extreme low frequency band protects neuronal and microglia cells from oxygen-glucose deprivation.","authors":"Paloma Mata, Stefano Calovi, Kami Pars Benli, Leyre Iglesias, María Isabel Hernández, Abraham Martín, Alberto Pérez-Samartín, Ander Ramos-Murguialday, María Domercq, Iñaki Ortego-Isasa","doi":"10.3389/fncel.2024.1455158","DOIUrl":"10.3389/fncel.2024.1455158","url":null,"abstract":"<p><p>Ischemic stroke consists of rapid neural death as a consequence of brain vessel obstruction, followed by damage to the neighboring tissue known as ischemic penumbra. The cerebral tissue in the core of the lesions becomes irreversibly damaged, however, the ischemic penumbra is potentially recoverable during the initial phases after the stroke. Therefore, there is real need for emerging therapeutic strategies to reduce ischemic damage and its spread to the penumbral region. For this reason, we tested the effect of Extreme Low Frequency Electromagnetic Stimulation (ELF-EMS) on <i>in vitro</i> primary neuronal and microglial cultures under oxygen-glucose deprivation (OGD) conditions. ELF-EMS under basal non-OGD conditions did not induce any effect in cell survival. However, ELF-EMS significantly reduced neuronal cell death in OGD conditions and reduced ischemic induced Ca²⁺ overload. Likewise, ELF-EMS modulated microglia activation and OGD-induced microglia cell death. Hence, this study suggests potential benefits in the application of ELF-EMS to limit ischemic irreversible damages under <i>in vitro</i> stroke conditions, encouraging <i>in vivo</i> preclinical validations of ELF-EMS as a potential therapeutic strategy for ischemic stroke.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1455158"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647421","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":"Effects of the two-pore potassium channel subunit Task5 on neuronal function and signal processing in the auditory brainstem.","authors":"Mahshid Helia Saber, Michaela Kaiser, Lukas Rüttiger, Christoph Körber","doi":"10.3389/fncel.2024.1463816","DOIUrl":"10.3389/fncel.2024.1463816","url":null,"abstract":"<p><p>Processing of auditory signals critically depends on the neuron's ability to fire brief, precisely timed action potentials (APs) at high frequencies and high fidelity for prolonged times. This requires the expression of specialized sets of ion channels to quickly repolarize neurons, prevent aberrant AP firing and tightly regulate neuronal excitability. Although critically important, the regulation of neuronal excitability has received little attention in the auditory system. Neuronal excitability is determined to a large extent by the resting membrane potential (RMP), which in turn depends on the kind and number of ion channels open at rest; mostly potassium channels. A large part of this resting potassium conductance is carried by two-pore potassium channels (K2P channels). Among the K2P channels, the subunit Task5 is expressed almost exclusively in the auditory brainstem, suggesting a specialized role in auditory processing. However, since it failed to form functional ion channels in heterologous expression systems, it was classified \"non-functional\" for a long time and its role in the auditory system remained elusive. Here, we generated Task5 knock-out (KO) mice. The loss of Task5 resulted in changes in neuronal excitability in bushy cells of the ventral cochlear nucleus (VCN) and principal neurons of the medial nucleus of the trapezoid body (MNTB). Moreover, auditory brainstem responses (ABRs) to loud sounds were altered in Tasko5-KO mice. Thus, our study provides evidence that Task5 is indeed a functional K2P subunit and contributes to sound processing in the auditory brainstem.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1463816"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650504","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":"Local delivery of soluble fractalkine (CX3CL1) peptide restores ribbon synapses after noise-induced cochlear synaptopathy.","authors":"Vijayprakash Manickam, Sibaprasad Maity, Sree Varshini Murali, Dinesh Y Gawande, Andrew R Stothert, Lyudamila Batalkina, Astrid E Cardona, Tejbeer Kaur","doi":"10.3389/fncel.2024.1486740","DOIUrl":"10.3389/fncel.2024.1486740","url":null,"abstract":"<p><p>Cochlear ribbon synapses between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are vulnerable to rapid and primary damage and/or loss due to noise overexposure. Such damaged ribbon synapses can repair spontaneously in mouse and guinea pig. However, the mechanisms for synaptic repair are unclear. Previously, we have demonstrated a critical role for the fractalkine signaling axis (CX₃CL1-CX₃CR1) in synaptic repair, wherein noise-damaged ribbon synapses are spontaneously repaired in the presence of fractalkine receptor (CX₃CR1) expressed by cochlear macrophages. Here, we examined whether local administration of chemokine fractalkine ligand (CX₃CL1 or FKN) in the form of a peptide is effective in restoring synapses and hearing loss after noise-induced cochlear synaptopathy (NICS). Specifically, the efficacy of different isoforms of FKN was evaluated for restoration of loss of IHC ribbon synapses and hearing after NICS. A single transtympanic injection of soluble isoform of FKN (sFKN) peptide at 1 day after synaptopathic noise trauma for 2 hours at 93 decibel sound pressure level led to significant recovery of auditory brainstem response (ABR) thresholds, ABR peak I amplitudes and ribbon synapses in FKN knockout mice when compared to mice injected with membrane-bound FKN peptide (mFKN). Likewise, local treatment with sFKN peptide in FKN wild type mice restored synaptopathic noise-damaged ribbon synapses and ABR peak I amplitudes. Mechanistically, FKN regulates macrophage numbers in the damaged cochlea and in the absence of macrophages, sFKN failed to restore loss of synapses and hearing after NICS. Furthermore, sFKN treatment attenuated cochlear inflammation after NICS without altering the expression of CX₃CR1. Finally, injected sFKN peptide was detectable inside the cochlea for 24 h localized to the basilar membrane and spiral lamina near the sensory epithelium. These data provide a proof-of-principle that local delivery of an immune factor, sFKN is effective in restoring ribbon synapses and hearing loss after NICS in a macrophage-dependent manner and highlights the potential of sFKN as an immunotherapy for cochlear synaptopathy due to noise.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1486740"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617641","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":"Piezo1: the key regulators in central nervous system diseases.","authors":"Yi Xu, Yuheng Wang, Yanling Yang, Xiaowei Fang, Lidong Wu, Jialing Hu, Jin Li, Shuchong Mei","doi":"10.3389/fncel.2024.1441806","DOIUrl":"10.3389/fncel.2024.1441806","url":null,"abstract":"<p><p>The occurrence and development of central nervous system (CNS) diseases is a multi-factor and multi-gene pathological process, and their diagnosis and treatment have always posed a serious challenge in the medical field. Therefore, exploring the relevant factors in the pathogenesis of CNS and improving the diagnosis and treatment rates has become an urgent problem. Piezo1 is a recently discovered mechanosensitive ion channel that opens in response to mechanical stimuli. A number of previous studies have shown that the Piezo channel family plays a crucial role in CNS physiology and pathology, especially in diseases related to CNS development and mechanical stimulation. This article comprehensively describes the biological properties of Piezo1, focuses on the potential association between Piezo1 and CNS disorders, and explores the pharmacological roles of Piezo1 agonists and inhibitors in treating CNS disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1441806"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617818","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 nociceptive-nociplastic spectrum of myofascial orofacial pain: insights from neuronal ion channel studies.","authors":"Nontawat Chuinsiri, Watcharaphol Tiskratok, Teekayu Plangkoon Jorns","doi":"10.3389/fncel.2024.1500427","DOIUrl":"10.3389/fncel.2024.1500427","url":null,"abstract":"<p><p>Myofascial orofacial pain, traditionally viewed as a nociceptive pain condition, also exhibits characteristics consistent with nociplastic pain-pain arising from altered nociception without clear evidence of tissue damage. Evidence supporting myofascial orofacial pain as nociplastic pain includes clinical observations of central sensitisation in patients, even in the absence of visible inflammation. Sensitisation is characterised by heightened responsiveness of nociceptive neurons to normal stimuli or activation by normally subthreshold stimuli, either in the peripheral or central nervous system. It is linked to maladaptive neuroplastic changes, including increased functional potentiation and altered expression of neuronal ion channels, receptors and neurotransmitters. This mini-review presents insights from existing evidence regarding altered nociception and its relation to changes in the expression of neuronal ion channels in myofascial orofacial pain. Increased expression of transient receptor potential (TRP) vanilloid 1 channels (TRPV1), TRPV4, TRP ankyrin 1 channels (TRPA1), Piezo2 channels, P2X3 purinergic receptors, N-Methyl-D-Aspartate (NMDA) receptors and voltage-gated calcium channels in the trigeminal ganglion of rodents has been observed in association with myofascial orofacial pain. This evidence highlights the role of neuronal ion channels in the pathophysiology of myofascial orofacial pain and supports the involvement of nociplastic mechanisms.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1500427"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617618","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":"Circadian rhythm disruption: a potential trigger in Parkinson's disease pathogenesis.","authors":"Ke Xu, Yu Zhang, Yue Shi, Yake Zhang, Chengguang Zhang, Tianjiao Wang, Peizhu Lv, Yan Bai, Shun Wang","doi":"10.3389/fncel.2024.1464595","DOIUrl":"10.3389/fncel.2024.1464595","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), abnormal accumulation of α-synuclein (α-syn), and activation of microglia leading to neuroinflammation. Disturbances in circadian rhythm play a significant role in PD, with most non-motor symptoms associated with disruptions in circadian rhythm. These disturbances can be observed years before motor symptoms appear and are marked by the emergence of non-motor symptoms related to PD, such as rapid eye movement sleep behavior disorder (RBD), restless leg syndrome (RLS), excessive daytime sleepiness (EDS), depression and anxiety, changes in blood pressure, gastrointestinal dysfunction, and urinary problems. Circadian rhythm disruption precedes the onset of motor symptoms and contributes to the progression of PD. In brief, this article outlines the role of circadian rhythm disruption in triggering PD at cellular and molecular levels, as well as its clinical manifestations. It also explores how circadian rhythm research can contribute to preventing the onset and progression of PD from current and future perspectives.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1464595"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617608","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":"Deficiency of NLRP3 protects cerebral pericytes and attenuates Alzheimer's pathology in tau-transgenic mice.","authors":"Wenqiang Quan, Yann Decker, Qinghua Luo, Axel Chemla, Hsin-Fang Chang, Dong Li, Klaus Fassbender, Yang Liu","doi":"10.3389/fncel.2024.1471005","DOIUrl":"10.3389/fncel.2024.1471005","url":null,"abstract":"<p><strong>Introduction: </strong>Activation of NLRP3-containing inflammasome, which is responsible for IL-1β maturation, has been shown to contribute to Alzheimer's disease (AD)-associated pathogenesis in both APP- and tau-transgenic mice. However, effects of NLRP3 on pericytes and subsequent cerebrovascular pathology in AD remain unknown.</p><p><strong>Methods: </strong>NLRP3-deficient and wild-type AD animal models were generated by crossing human P301S tau-transgenic mice and <i>Nlrp3</i> knockout mice. AD-associated neuroinflammation, tauopathy, vasculature and pericyte coverage in the brain were investigated using immunohistological and molecular biological methods. To investigate how NLRP3 regulates pericyte activation and survival, pericytes from the brains of <i>Nlrp3</i> knockout and wild-type mice were cultured, treated with IL-1β and H₂O₂ at different concentrations and analyzed by confocal microscopy and flow cytometry after staining with fluorescently labelled phalloidin, annexin-V and PDGFRβ antibody.</p><p><strong>Results: </strong>Deficiency of NLRP3 (1) reduced Iba-1, GFAP and AT8 antibody-immunoreactive phosphorylated tau-positive cells, without significantly altering transcription of inflammatory genes, (2) preserved cerebral vasculature and pericyte coverage and up-regulated <i>Osteopontin</i> gene transcription, and (3) improved cognitive function in tau-transgenic mice. In cell culture, NLRP3 deficiency prevented pericyte apoptosis. Treatment with IL-1β or H₂O₂ increased the expression of PDGFRβ in NLRP3-deficient pericytes, but decreased it in NLRP3 wild-type pericytes in a dose-dependent manner.</p><p><strong>Discussion: </strong>Inhibition of NLRP3 can promote pericyte survival, improve cerebrovascular function, and attenuate AD pathology in the brain of tau-transgenic mice. Our study supports NLRP3 as a novel therapeutic target for Alzheimer's patients.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1471005"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617626","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":"Application of an <i>in vitro</i> neuroinflammation model to evaluate the efficacy of magnesium-lithium alloys.","authors":"Krathika Bhat, Heike Helmholz, Regine Willumeit-Römer","doi":"10.3389/fncel.2024.1485427","DOIUrl":"10.3389/fncel.2024.1485427","url":null,"abstract":"<p><p>Mg-Li alloys can be promising candidates as bioresorbable Li-releasing implants for bipolar disorder and other neurodegenerative disorders. In order to compare the therapeutic efficacy of conventional Li salts and Li delivered through Mg-Li alloy extracts, we tested an <i>in vitro</i> model based on the neuroinflammation hypothesis of mood disorders (peripheral inflammation inducing neuroinflammation) wherein, a coculture of microglia and astrocytes was treated with conditioned medium from pro-inflammatory macrophages. Two alloys, Mg-1.6Li and Mg-9.5Li, were tested in the form of material extracts and well-known outcomes of Li treatment such as GSK3β phosphorylation (indirect flow cytometry) and influence on inflammation-related gene expression (qPCR) were compared against Li salts. This is the first study demonstrating that Li can increase the phosphorylation of GSK3β in glial cells in the presence of excess Mg. Furthermore, Mg-Li alloys were more effective than Li salts in downregulating <i>IL6</i> and upregulating the neurotrophin <i>GDNF</i>. Mg had no antagonistic effects toward Li-driven downregulation of astrogliosis markers. Overall, the results provide evidence to support further studies employing Mg-Li alloys for neurological applications.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1485427"},"PeriodicalIF":4.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617602","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}