Frontiers in Cellular Neuroscience最新文献

{"title":"Pivotal roles of melanopsin containing retinal ganglion cells in pupillary light reflex in photopic conditions.","authors":"Jeremy Matthew Bohl, Abdul Rhman Hassan, Zachary J Sharpe, Megi Kola, Angela Shehu, Deborah Langrill Beaudoin, Tomomi Ichinose","doi":"10.3389/fncel.2025.1547066","DOIUrl":"10.3389/fncel.2025.1547066","url":null,"abstract":"<p><p>The pupillary light reflex (PLR) is crucial for protecting the retina from excess light. The intrinsically photosensitive retinal ganglion cells (ipRGCs) in the retina are neurons that are critical to generating the PLR, receiving rod/cone photoreceptor signals and directly sensing light through melanopsin. Previous studies have investigated the roles of photoreceptors and ipRGCs in PLR using genetically-modified mouse models. Herein, we acutely ablated photoreceptors using N-nitroso-N-methylurea (MNU) to examine the roles of ipRGCs in the PLR. We conducted PLR and multiple electrode array (MEA) recordings evoked by three levels of light stimuli before and 5 days after MNU intraperitoneal (i.p..) injection using C57BL6/J wildtype (WT) mice. We also conducted these measurements using the rod & cone dysfunctional mice (Gnat1^-/- & Cnga3^-/-:dKO) to compare the results to published studies in which mutant mice were used to show the role of photoreceptors and ipRGCs in PLR. PLR pupil constriction increased as the light stimulus intensified in WT mice. In MNU mice, PLR was not induced by the low light stimulus, suggesting that photoreceptors induced the PLR at this light intensity. By contrast, the high light stimulus fully induced PLR, similar to the response in WT mice. In dKO mice, no PLR was evoked by the low-light stimulus and a slow-onset PLR was evoked by the high-light stimulus, consistent with previous reports. <i>Ex vivo</i> MEA recording in the MNU tissue revealed a population of ipRGCs with a fast onset and peak time, suggesting that they drove the fast PLR response. These results suggest that ipRGCs primarily contribute to the PLR at a high light intensity, which does not agree with the previous results shown by mutant mouse models. Our results indicate that the melanopsin response in ipRGCs generate fast and robust PLR when induced by high light.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1547066"},"PeriodicalIF":4.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482662","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":"miRNA in blood-brain barrier repair: role of extracellular vesicles in stroke recovery.","authors":"Vojtech Sprincl, Nataliya Romanyuk","doi":"10.3389/fncel.2025.1503193","DOIUrl":"10.3389/fncel.2025.1503193","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of mortality and long-term disability globally. One of its aspects is the breakdown of the blood-brain barrier (BBB). The disruption of BBB's integrity during stroke exacerbates neurological damage and hampers therapeutic intervention. Recent advances in regenerative medicine suggest that mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) show promise for restoring BBB integrity. This review explores the potential of MSC-derived EVs in mediating neuroprotective and reparative effects on the BBB after ischemic stroke. We highlight the molecular cargo of MSC-derived EVs, including miRNAs, and their role in enhancing angiogenesis, promoting the BBB and neural repair, and mitigating apoptosis. Furthermore, we discuss the challenges associated with the clinical translation of MSC-derived EV therapies and the possibilities of further enhancing EVs' innate protective qualities. Our findings underscore the need for further research to optimize the therapeutic potential of EVs and establish their efficacy and safety in clinical settings.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1503193"},"PeriodicalIF":4.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482661","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":"Integrated bioinformatics analysis of the effects of chronic pain on patients with spinal cord injury.","authors":"Jinlong Zhang, Longju Qi, Yuyu Sun, Shiyuan Chen, Jinyi Liu, Jiaxi Chen, Fangsu Yan, Wenqi Wang, Qinghua Wang, Liang Chen","doi":"10.3389/fncel.2025.1457740","DOIUrl":"10.3389/fncel.2025.1457740","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) poses a substantial challenge in contemporary medicine, significantly impacting patients and society. Emerging research highlights a strong association between SCI and chronic pain, yet the molecular mechanisms remain poorly understood. To address this, we conducted bioinformatics and systems biology analyses to identify molecular biomarkers and pathways that link SCI to chronic pain. This study aims to elucidate these mechanisms and identify potential therapeutic targets.</p><p><strong>Methods: </strong>Through analysis of the GSE151371 and GSE177034 databases, we identified differentially expressed genes (DEGs) linked to SCI and chronic pain. This analysis uncovered shared pathways, proteins, transcription factor networks, hub genes, and potential therapeutic drugs. Regression analysis on the hub genes facilitated the development of a prognostic risk model. Additionally, we conducted an in-depth examination of immune infiltration in SCI to elucidate its correlation with chronic pain.</p><p><strong>Results: </strong>Analyzing 101 DEGs associated with SCI and chronic pain, we constructed a protein interaction network and identified 15 hub genes. Using bioinformatics tools, we further identified 4 potential candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed a strong correlation between SCI and chronic pain, particularly related to inflammation. Additionally, we examined the relationship between SCI and immune cell infiltration, discovering a significant link between SCI and T cell activation. This is notable as activated T cells can cause persistent inflammation and chronic pain. Lastly, we analyzed the hub genes to explore the transcription factor network, potential therapeutic drugs, and ceRNA networks.</p><p><strong>Conclusion: </strong>The analysis of 15 hub genes as significant biological markers for SCI and chronic pain has led to the identification of several potential drugs for treatment.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1457740"},"PeriodicalIF":4.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457445","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: New insights into intracellular pathways and therapeutic targets in CNS diseases.","authors":"Lisa Gherardini","doi":"10.3389/fncel.2025.1559821","DOIUrl":"10.3389/fncel.2025.1559821","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1559821"},"PeriodicalIF":4.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448745","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":"Tight junction proteins in glial tumors development and progression.","authors":"Jakub Moskal, Slawomir Michalak","doi":"10.3389/fncel.2025.1541885","DOIUrl":"10.3389/fncel.2025.1541885","url":null,"abstract":"<p><p>Tight junctions form a paracellular barrier in epithelial and endothelial cells, and they regulate the diffusion of fluids, molecules, and the penetration of cells across tissue compartments. Tight junctions are composed of a group of integral membrane proteins, which include the claudin family, tight junction-associated Marvel protein family, junctional adhesion molecule family, and proteins that anchor the cytoskeleton, such as <i>zonula occludens</i> proteins and the cingulin family. Several factors, such as neurotransmitters or cytokines, and processes like ischemia/hypoxia, inflammation, tumorigenesis, phosphorylation/dephosphorylation, ubiquitination, and palmitoylation, regulate tight junction proteins. Claudins are involved in tumorigenesis processes that lead to glioma formation. In gliomas, there is a noticeable dysregulation of claudins, occludin, and <i>zonula occludens-1</i> abundance, and their dislocation has been observed. The weakening of intercellular adhesion and cell detachment is responsible for glioma infiltration into surrounding tissues. Furthermore, the paracellular permeability of the blood-brain barrier, formed with the involvement of tight junction proteins, influences the development of peritumoral edema - and, simultaneously, the rate of drug delivery to the glial tumor. Understanding the junctional and paracellular environments in brain tumors is crucial to predicting glial tumor progression and the feasibility of chemotherapeutic drug delivery. This knowledge may also illuminate differences between high and low-grade gliomas.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1541885"},"PeriodicalIF":4.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440451","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":"<i>N</i> ¹-methylnicotinamide promotes age-related cochlear damage via the overexpression of SIRT1.","authors":"Toru Miwa, Akihito Tarui, Teppei Kouga, Yasunori Asai, Hideaki Ogita, Taro Fujikawa, Nobuhiro Hakuba","doi":"10.3389/fncel.2025.1542164","DOIUrl":"10.3389/fncel.2025.1542164","url":null,"abstract":"<p><p>Age-related hearing loss (ARHL) is a complex condition with genetic, aging, and environmental influences. Sirtuins, particularly SIRT1, are NAD-dependent protein deacetylases critical to aging and stress responses. SIRT1 is modulated by nicotinamide N-methyltransferase (NNMT) and its product, N¹-methylnicotinamide (MNAM), which influence ARHL progression. While SIRT1 is protective under certain conditions, its overexpression may paradoxically exacerbate hearing loss. This study examines MNAM supplementation's impact on SIRT1 expression and ARHL in low-fat diet (LFD)-fed B6 and CBA mice. Mice were divided into LFD and LFD + MNAM groups and evaluated for auditory function, cochlear morphology, metabolic profiles, and SIRT1 expression at 3, 6, and 12 months of age. MNAM supplementation accelerated ARHL in both strains, with B6 mice showing more pronounced and earlier disease progression. Auditory brainstem response (ABR) thresholds were significantly elevated, and distortion-product otoacoustic emissions (DPOAE) indicated outer hair cell dysfunction. Cochlear histology revealed reduced hair cell and spiral ganglion cell counts, as well as decreased Na⁺/K⁺-ATPase α1 expression and endocochlear potential. MNAM increased SIRT1 protein levels in the cochlea without altering Sirt1 mRNA, suggesting post-transcriptional regulation. Metabolomic analysis revealed disrupted mitochondrial and oxidative pathways, including fatty acid oxidation and gluconeogenesis. Tricarboxylic acid (TCA) cycle dysregulation was evident, particularly in B6 mice, with elevated pyruvate, fumarate, and lactate levels. Despite similar metabolic trends in CBA mice, their slower aging profiles mitigated ARHL progression. These results suggest that while moderate SIRT1 expression protects against ARHL, overexpression disrupts metabolic homeostasis, accelerating cochlear aging and dysfunction. The dual role of SIRT1 emphasizes the need for precise modulation of its expression for effective therapeutic interventions. Future research should explore mechanisms underlying SIRT1-induced cochlear damage and strategies to maintain balanced SIRT1 expression. This study highlights MNAM's detrimental effects on ARHL, underscoring its significance for developing targeted approaches to delay ARHL onset and preserve auditory function.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1542164"},"PeriodicalIF":4.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432736","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":"Enhancing sleep quality in synucleinopathies through physical exercise.","authors":"Jacopo Canonichesi, Laura Bellingacci, Francesco Rivelli, Alessandro Tozzi","doi":"10.3389/fncel.2025.1515922","DOIUrl":"10.3389/fncel.2025.1515922","url":null,"abstract":"<p><p>During sleep, several crucial processes for brain homeostasis occur, including the rearrangement of synaptic connections, which is essential for memory formation and updating. Sleep also facilitates the removal of neurotoxic waste products, the accumulation of which plays a key role in neurodegeneration. Various neural components and environmental factors regulate and influence the physiological transition between wakefulness and sleep. Disruptions in this complex system form the basis of sleep disorders, as commonly observed in synucleinopathies. Synucleinopathies are neurodegenerative disorders characterized by abnormal build-up of <i>α</i>-synuclein protein aggregates in the brain. This accumulation in different brain regions leads to a spectrum of clinical manifestations, including hypokinesia, cognitive impairment, psychiatric symptoms, and neurovegetative disturbances. Sleep disorders are highly prevalent in individuals with synucleinopathies, and they not only affect the overall well-being of patients but also directly contribute to disease severity and progression. Therefore, it is crucial to develop effective therapeutic strategies to improve sleep quality in these patients. Adequate sleep is vital for brain health, and the role of synucleinopathies in disrupting sleep patterns must be taken into account. In this context, it is essential to explore the role of physical exercise as a potential non-pharmacological intervention to manage sleep disorders in individuals with synucleinopathies. The current evidence on the efficacy of exercise programs to enhance sleep quality in this patient population is discussed.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1515922"},"PeriodicalIF":4.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432738","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 spatial buildup of nonlinear compression in the cochlea.","authors":"Kostas Kondylidis, Anna Vavakou, Marcel van der Heijden","doi":"10.3389/fncel.2024.1450115","DOIUrl":"10.3389/fncel.2024.1450115","url":null,"abstract":"<p><p>In the mammalian cochlea, the transduction from vibrations to inner hair cell receptor currents is preceded by a stage of mechanical pre-processing that involves a rapid, strongly nonlinear compression. The mechanisms by which the cochlea realizes this dynamic compression are still poorly understood. Previous work by our group suggested that compression does not occur locally, but is realized by a cascade of weakly nonlinear elements along the cochlear partition. The resulting progressive accumulation of nonlinearity was termed the spatial buildup of compression. Here we studied mechanical compression in the basal turn of the sensitive gerbil cochlea using optical coherence tomography. We recorded vibrations at multiple positions along the length of the cochlear partition. Such longitudinal studies were virtually impossible with previous techniques. Using a tailored two-tone stimulus we quantified the spatial profile of compression. We found that the amount of compression grew gradually in an intensity-dependent fashion along our measurement stretch, as we moved apically toward the place of maximum vibration. This gradual buildup of compression was not mirrored by a gradual reduction beyond the peak. In fact the amount of compression accumulated even beyond the peak. This asymmetric pattern supports the view that mechanical compression is realized in a cascaded, distributed fashion which hinges on the traveling wave nature of cochlear vibrations.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1450115"},"PeriodicalIF":4.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406580","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 role of neurotrophic factors in retinal ganglion cell resiliency.","authors":"Alan K Abraham, Michael Telias","doi":"10.3389/fncel.2025.1536452","DOIUrl":"10.3389/fncel.2025.1536452","url":null,"abstract":"<p><p>Many retinal diseases are characterized by direct or indirect retinal ganglion cell (RGC) neurodegeneration. In glaucoma and optic nerve neuropathies, RGCs are the primary affected cells, whereas in photoreceptor dystrophies, RGC loss is secondary to the death of rods and cones. The death of RGCs in either case will irreversibly cause loss of vision, as RGCs are the sole output neurons of the retina. RGC neurodegeneration affects certain neurons preferentially, resulting in subpopulations of resilient and susceptible cells. Neurotrophins (NTs) are known to mediate neuronal survival through the downstream activation of various anti-apoptotic pathways. In this review, we summarize the current methods of RGC identification and quantification in animal models of direct or indirect neurodegeneration, and describe the advantages and disadvantages associated with these techniques. Using these techniques, multiple studies have uncovered the potential role of NTs in protecting RGCs during direct neurodegeneration, with BDNF and NGF delivery promoting RGC survival in models of experimental glaucoma. Many fewer studies have addressed similar questions in retinal diseases where RGC loss is secondary to photoreceptor degeneration, yielding conflicting results. Our analysis suggests that these seemingly contradictory results can be explained by the varying onset and geographic distribution of photoreceptor death.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1536452"},"PeriodicalIF":4.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406646","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":"Long-term live-cell imaging of GFAP+ astroglia and laminin+ vessels in organotypic mouse brain slices using microcontact printing.","authors":"Christian Humpel","doi":"10.3389/fncel.2025.1540150","DOIUrl":"10.3389/fncel.2025.1540150","url":null,"abstract":"<p><p>Organotypic brain slices are three-dimensional, 150-μm-thick sections derived from postnatal day 10 mice that can be cultured for several weeks <i>in vitro</i>. However, these slices pose challenges for live-cell imaging due to their thickness, particularly without access to expensive two-photon microscopy. In this study, we present an innovative method to label and visualize specific brain cell populations in living slices. Using microcontact printing, antibodies are applied directly onto the slices in a controlled 400-μm-diameter pattern. Astrocytes are labeled with glial fibrillary acidic protein (GFAP), and vessels are labeled with laminin. Subsequently, slices are incubated with secondary fluorescent antibodies (green fluorescent Alexa-488 or red fluorescent Alexa-546) and visualized using an inverted fluorescence microscope. This approach offers a cost-effective and detailed visualization technique for astroglia and vessels in living brain slices, enabling investigation to be conducted over several weeks.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1540150"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398622","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}