Frontiers in Cellular Neuroscience最新文献

{"title":"The effects of locus coeruleus ablation on mouse brain volume and microstructure evaluated by high-field MRI.","authors":"Rasmus West Knopper, Christian Stald Skoven, Simon Fristed Eskildsen, Leif Østergaard, Brian Hansen","doi":"10.3389/fncel.2024.1498133","DOIUrl":"10.3389/fncel.2024.1498133","url":null,"abstract":"<p><p>The locus coeruleus (LC) produces most of the brain's noradrenaline (NA). Among its many roles, NA is often said to be neuroprotective and important for brain upkeep. For this reason, loss of LC integrity is thought to impact brain volume and microstructure as well as plasticity broadly. LC dysfunction is also a suspected driver in the development of neurodegenerative diseases. Nevertheless, the impact of LC dysfunction on the gross structure and microstructure of normal brains is not well-studied. We employed high-field ex vivo magnetic resonance imaging (MRI) to investigate brain volumetrics and microstructure in control (CON) mice and mice with LC ablation (LCA) at two ages, representing the developing brain and the fully matured brain. These whole-brain methods are known to be capable of detecting subtle morphological changes and brain microstructural remodeling. We found mice behavior consistent with histologically confirmed LC ablation. However, MRI showed no difference between CON and LCA groups with regard to brain size, relative regional volumes, or regional microstructural indices. Our findings suggest that LC-NA is not needed for postnatal brain maturation and growth in mice. Nor is it required for maintenance in the normal adult mouse brain, as no atrophy or microstructural aberration is detected after weeks of LC dysfunction. This adds clarity to the often-encountered notion that LC-NA is important for brain \"trophic support\" as it shows that such effects are likely most relevant to mechanisms related to brain plasticity and neuroprotection in the (pre)diseased brain.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1498133"},"PeriodicalIF":4.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893232","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":"Müller cells and retinal angiogenesis: critical regulators in health and disease.","authors":"Alan E Medina-Arellano, Jesús Silvestre Albert-Garay, Tania Medina-Sánchez, Karla Hernández Fonseca, Matilde Ruiz-Cruz, Lenin Ochoa-de la Paz","doi":"10.3389/fncel.2024.1513686","DOIUrl":"10.3389/fncel.2024.1513686","url":null,"abstract":"<p><p>Müller cells are the most abundant glial cells in the mammalian retina. Their morphology and metabolism enable them to be in close contact and interact biochemically and physically with almost all retinal cell types, including neurons, pericytes, endothelial cells, and other glial cells, influencing their physiology by releasing bioactive molecules. Studies indicate that Müller glial cells are the primary source of angiogenic growth factor secretion in the neuroretina. Because of this, over the past decade, it has been postulated that Müller glial cells play a significant role in maintaining retinal vascular homeostasis, with potential implications in vasoproliferative retinopathies. This review aims to summarize the current understanding of the mechanisms by which Müller glial cells influence retinal angiogenesis in health and disease, with a particular emphasis on three of the retinopathies with the most significant impact on visual health worldwide: diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1513686"},"PeriodicalIF":4.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884804","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 impact of COVID-19 on accelerating of immunosenescence and brain aging.","authors":"Ludmila Müller, Svetlana Di Benedetto","doi":"10.3389/fncel.2024.1471192","DOIUrl":"10.3389/fncel.2024.1471192","url":null,"abstract":"<p><p>The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1471192"},"PeriodicalIF":4.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885012","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":"Fractionated alpha and mixed beam radiation promote stronger pro-inflammatory effects compared to acute exposure and trigger phagocytosis.","authors":"Mostafa Karimi Roshan, Sergey Belikov, Melissa Ix, Nicoletta Protti, Claudia Balducci, Richard Dodel, J Alexander Ross, Lovisa Lundholm","doi":"10.3389/fncel.2024.1440559","DOIUrl":"10.3389/fncel.2024.1440559","url":null,"abstract":"<p><strong>Introduction and methods: </strong>Aiming to evaluate safety aspects of a recently proposed approach to target Alzheimer's disease, we mimicked a complex boron neutron capture therapy field using a mixed beam consisting of high- and low-linear energy transfer (LET) radiation, ²⁴¹Am alpha particles (α) and/or X-ray radiation respectively, in human microglial (HMC3) cells.</p><p><strong>Results: </strong>Acute exposure to 2 Gy X-rays induced the strongest response in the formation of γH2AX foci 30 min post irradiation, while α- and mixed beam-induced damage (α:X-ray = 3:1) sustained longer. Fractionation of the same total dose (0.4 Gy daily) induced a similar number of γH2AX foci as after acute radiation, however, α- or mixed irradiation caused a higher expression of DNA damage response genes CDKN1A and MDM2 24 h after the last fraction, as well as a stronger decrease in cell viability and clonogenic survival compared to acute exposure. Phosphorylation of STING, followed by phosphorylation of NF-κB subunit p65, was rapidly induced (1 or 3 h, respectively) after the last fraction by all radiation qualities. This led to IL-1β secretion into the medium, strongly elevated expression of pro-inflammatory cytokine genes and enhanced phagocytosis after fractionated exposure to α- and mixed beam-irradiation compared to their acute counterparts 24 h post-irradiation. Nevertheless, all inflammatory changes were returning to basal levels or below 10-14 days post irradiation.</p><p><strong>Discussion: </strong>In conclusion, we demonstrate strong transient pro-inflammatory induction by daily high-LET radiation in a microglia model, triggering phagocytosis which may aid in clearing amyloid beta, but importantly, from a safety perspective, without long-term alterations.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1440559"},"PeriodicalIF":4.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881698","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: Extracellular vesicles: emerging roles in the aged and neurodegenerative brain.","authors":"Foteini Vasilopoulou, Jennifer Pocock, Gal Bitan, Dirk M Hermann","doi":"10.3389/fncel.2024.1522499","DOIUrl":"10.3389/fncel.2024.1522499","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1522499"},"PeriodicalIF":4.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881785","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 Aβ₄₂:Aβ₄₀ ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction.","authors":"Annika Haessler, Stefanie Gier, Nathalie Jung, Maike Windbergs","doi":"10.3389/fncel.2024.1516093","DOIUrl":"10.3389/fncel.2024.1516093","url":null,"abstract":"<p><p>The pathophysiological role of Aβ₄₂ oligomers in the onset of Alzheimer's disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ₄₂ and Aβ₄₀, which is more abundant but less aggregation-prone. This study investigates Aβ₄₂:Aβ₄₀ oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood-brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of Aβ₄₀ on Aβ₄₂ fibrillation, suggesting an inhibitory effect on aggregation. Mixed oligomers, especially with low proportions of Aβ₄₂, were equally detrimental as pure Aβ₄₂ oligomers regarding cell viability, functionality, and metabolism. They also differentially affected lipid droplet metabolism in BBB-associated microglia, indicating distinct pathophysiological responses. Our findings demonstrate the overarching significance of the Aβ₄₂:Aβ₄₀ ratio in Aβ oligomers, challenging the traditional focus on Aβ₄₂ in AD research.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1516093"},"PeriodicalIF":4.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881703","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: Mechanisms of neurodegeneration in amyotrophic lateral sclerosis and related disorders.","authors":"Danyllo Oliveira, Agnes Lumi Nishimura","doi":"10.3389/fncel.2024.1531449","DOIUrl":"https://doi.org/10.3389/fncel.2024.1531449","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1531449"},"PeriodicalIF":4.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863858","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":"Aging promotes an increase in mitochondrial fragmentation in astrocytes.","authors":"Ana Paula Bergamo Araujo, Gabriele Vargas, Lívia de Sá Hayashide, Isadora Matias, Cherley Borba Vieira Andrade, Jorge José de Carvalho, Flávia Carvalho Alcantara Gomes, Luan Pereira Diniz","doi":"10.3389/fncel.2024.1496163","DOIUrl":"10.3389/fncel.2024.1496163","url":null,"abstract":"<p><strong>Introduction: </strong>Brain aging involves a complex interplay of cellular and molecular changes, including metabolic alterations and the accumulation of senescent cells. These changes frequently manifest as dysregulation in glucose metabolism and mitochondrial function, leading to reduced energy production, increased oxidative stress, and mitochondrial dysfunction-key contributors to age-related neurodegenerative diseases.</p><p><strong>Methods: </strong>We conducted experiments on two models: young (3-4 months) and aged (over 18 months) mice, as well as cultures of senescent and control mouse astrocytes. Mitochondrial content and biogenesis were analyzed in astrocytes and neurons from aged and young animals. Cultured senescent astrocytes were examined for mitochondrial membrane potential and fragmentation. Quantitative PCR (qPCR) and immunocytochemistry were used to measure fusion- and fission-related protein levels. Additionally, transmission electron microscopy provided morphological data on mitochondria.</p><p><strong>Results: </strong>Astrocytes and neurons from aged animals showed a significant reduction in mitochondrial content and a decrease in mitochondrial biogenesis. Senescent astrocytes in culture exhibited lower mitochondrial membrane potential and increased mitochondrial fragmentation. qPCR and immunocytochemistry analyses revealed a 68% increase in fusion-related proteins (mitofusin 1 and 2) and a 10-fold rise in DRP1, a key regulator of mitochondrial fission. Transmission electron microscopy showed reduced perimeter, area, and length-to-diameter ratio of mitochondria in astrocytes from aged mice, supported by elevated DRP1 phosphorylation in astrocytes of the cerebral cortex.</p><p><strong>Discussion: </strong>Our findings provide novel evidence of increased mitochondrial fragmentation in astrocytes from aged animals. This study sheds light on mechanisms of astrocytic metabolic dysfunction and mitochondrial dysregulation in brain aging, highlighting mitochondrial fragmentation as a potential target for therapeutic interventions in age-related neurodegenerative diseases.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1496163"},"PeriodicalIF":4.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863857","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":"Neuronal activity inhibits mitochondrial transport only in synaptically connected segments of the axon.","authors":"Tom Venneman, Pieter Vanden Berghe","doi":"10.3389/fncel.2024.1509283","DOIUrl":"10.3389/fncel.2024.1509283","url":null,"abstract":"<p><p>Due to their large scale and uniquely branched architecture, neurons critically rely on active transport of mitochondria in order to match energy production and calcium buffering to local demand. Consequently, defective mitochondrial trafficking is implicated in various neurological and neurodegenerative diseases. A key signal regulating mitochondrial transport is intracellular calcium. Elevated Ca²⁺ levels have been demonstrated to inhibit mitochondrial transport in many cell types, including neurons. However, it is currently unclear to what extent calcium-signaling regulates axonal mitochondrial transport during realistic neuronal activity patterns. We created a robust pipeline to quantify with high spatial resolution, absolute Ca²⁺ concentrations. This allows us to monitor Ca²⁺ dynamics with pixel precision in the axon and other neuronal compartments. We found that axonal calcium levels scale with firing frequency in the range of 0.1-1 μM, whereas KCl-induced depolarization generated levels almost a magnitude higher. As expected, prolonged KCl-induced depolarization did inhibit axonal mitochondrial transport in primary hippocampal neurons. However, physiologically relevant neuronal activity patterns only inhibited mitochondrial transport in axonal segments which made connections to a target neuron. In \"non-connecting\" axonal segments, we were unable to trigger this inhibitory mechanism using realistic firing patterns. Thus, we confirm that neuronal activity can indeed regulate axonal mitochondrial transport, and reveal a spatial pattern to this regulation which went previously undetected. Together, these findings indicate a potent, but localized role for activity-related calcium fluctuations in the regulation of axonal mitochondrial transport.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1509283"},"PeriodicalIF":4.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853684","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":"MorphoGlia, an interactive method to identify and map microglia morphologies, demonstrates differences in hippocampal subregions of an Alzheimer's disease mouse model.","authors":"Juan Pablo Maya-Arteaga, Humberto Martínez-Orozco, Sofía Diaz-Cintra","doi":"10.3389/fncel.2024.1505048","DOIUrl":"10.3389/fncel.2024.1505048","url":null,"abstract":"<p><p>Microglia are dynamic central nervous system cells crucial for maintaining homeostasis and responding to neuroinflammation, as evidenced by their varied morphologies. Existing morphology analysis often fails to detect subtle variations within the full spectrum of microglial morphologies due to their reliance on predefined categories. Here, we present MorphoGlia, an interactive, user-friendly pipeline that objectively characterizes microglial morphologies. MorphoGlia employs a machine learning ensemble to select relevant morphological features of microglia cells, perform dimensionality reduction, cluster these features, and subsequently map the clustered cells back onto the tissue, providing a spatial context for the identified microglial morphologies. We applied this pipeline to compare the responses between saline solution (SS) and scopolamine (SCOP) groups in a SCOP-induced mouse model of Alzheimer's disease, with a specific focus on the hippocampal subregions CA1 and Hilus. Next, we assessed microglial morphologies across four groups: SS-CA1, SCOP-CA1, SS-Hilus, and SCOP-Hilus. The results demonstrated that MorphoGlia effectively differentiated between SS and SCOP-treated groups, identifying distinct clusters of microglial morphologies commonly associated with pro-inflammatory states in the SCOP groups. Additionally, MorphoGlia enabled spatial mapping of these clusters, identifying the most affected hippocampal layers. This study highlights MorphoGlia's capability to provide unbiased analysis and clustering of microglial morphological states, making it a valuable tool for exploring microglial heterogeneity and its implications for central nervous system pathologies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1505048"},"PeriodicalIF":4.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853682","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}