Frontiers in Cellular Neuroscience最新文献

{"title":"Spinal astrocytes involved in the pathogenesis and treatment of neuropathic pain.","authors":"Xiangmiao Li, Yushan Huang, Jinzhu Bai","doi":"10.3389/fncel.2025.1547524","DOIUrl":"10.3389/fncel.2025.1547524","url":null,"abstract":"<p><p>Neuropathic pain is a common and severe type of chronic pain, and its pathogenesis has not been fully defined. Increasing evidence shows that spinal astrocytes play indispensable roles in the occurrence and development of neuropathic pain. Most studies have suggested that activated astrocytes can crosstalk with other glial cells and neurons through morphological and functional changes, exacerbating the development of pain. However, reactive astrocytes have a dual role. As a defense mechanism, reactive astrocytes have roles in increasing neuroprotection and stimulating neurogenesis. Studies have demonstrated a potentially beneficial role for astrocyte activation in neuropathic pain. In addition, the therapeutic mechanisms of multiple drugs and neuromodulatory techniques are thought to be related to astrocytes. This review highlights the recent advances and significance of spinal astrocytes, emphasizing the need for a better understanding of their roles in the pathogenesis and treatment of neuropathic pain.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1547524"},"PeriodicalIF":4.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585087","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: Glial cells in health and disease: impacts on neural circuits and plasticity.","authors":"Shirin Hosseini, Poonam Thakur, David L Cedeno, Masoud Fereidoni, Mahmoud Elahdadi Salmani","doi":"10.3389/fncel.2025.1569725","DOIUrl":"10.3389/fncel.2025.1569725","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1569725"},"PeriodicalIF":4.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572668","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 autophagy mitigates LPS-induced neuroinflammation by inhibiting microglial M1 polarization and neuronophagocytosis.","authors":"Jingjing Guo, Yun Li, Kun Ma, Guohai Su","doi":"10.3389/fncel.2025.1546848","DOIUrl":"10.3389/fncel.2025.1546848","url":null,"abstract":"<p><strong>Background: </strong>Autophagy, a regulator of inflammation, has been implicated in various central nervous system pathologies. Despite this, the role and mechanisms of autophagy in lipopolysaccharide (LPS)-induced neuroinflammation are not clear. This study investigated whether autophagy can play a neuroprotective role in LPS-induced neuroinflammation.</p><p><strong>Methods: </strong>Primary microglial cells and male C57BL/6 J mice were treated with LPS, autophagy inhibitors (3-methyladenine, 3-MA), or autophagy activators (rapamycin). Cell viability, NF-κB pathway activation, pro-inflammatory cytokine expression, M1 polarization, autophagy markers, and neuronal damage were evaluated via various techniques including CCK-8 assay, Western blot analysis, ELISA, immunohistochemistry, and histological staining.</p><p><strong>Results: </strong>LPS (1 μg/mL) effectively inhibited cell viability, stimulated the expression of IκB-α and NF-κB, and simultaneously suppressed autophagy protein expression. The pro-inflammatory cytokines IL-1β and IL-6 showed a significant increase. Contrary to the effect of 3-MA, the rapamycin treatment inhibited the polarization of microglia cells to the M1 type in the various groups of microglia cells after LPS stimulation. This was evidenced by decreased expression of cytokines IL-1β, IL-6, and CD86, and increased expression of Arg-1, IL-10, and CD206. <i>In vivo</i> experiments found that mice with injections of LPS and 3-MA in the lateral ventricle showed significantly increased expression of IκB-α and NF-κB in brain tissues, elevated levels of pro-inflammatory cytokines, decreased autophagy levels, and increased necrotic neurons. There was increased aggregation of microglia cells and increased neuronophagocytosis. Conversely, mice injected with rapamycin showed enhanced neuronal cell autophagy, decreased expression of pro-inflammatory cytokines and apoptosis, and reduced neuronophagocytosis.</p><p><strong>Conclusion: </strong>Enhancing autophagy can effectively mitigate LPS-induced neuroinflammation by inhibiting microglial M1 polarization and neuronophagocytosis, thereby protecting neuronal integrity. These findings suggest potential therapeutic strategies targeting autophagy in neuroinflammatory conditions.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1546848"},"PeriodicalIF":4.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572670","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":"Neuron identity switches in response to the gradient gene expression pathway.","authors":"Gustavo Guzmán, Omar Paredes, Rebeca Romo-Vázquez, Hugo Vélez-Pérez, J Alejandro Morales","doi":"10.3389/fncel.2025.1536444","DOIUrl":"10.3389/fncel.2025.1536444","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1536444"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566657","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":"Rodent islet amyloid polypeptide (IAPP) selectively enhances GABA _<i>A</i> receptor-mediated neuronal inhibition in mouse ventral but not dorsal hippocampal dentate gyrus granule cells.","authors":"Olga Netsyk, Sergiy V Korol, Gunilla T Westermark, Bryndis Birnir, Zhe Jin","doi":"10.3389/fncel.2025.1531790","DOIUrl":"10.3389/fncel.2025.1531790","url":null,"abstract":"<p><p>Islet amyloid polypeptide (IAPP, amylin) is a peptide hormone that plays an important role in glucose homeostasis but has been implicated in the pathophysiology of type 2 diabetes and Alzheimer's disease. However, its effect on neurotransmission in the hippocampus remains poorly understood. Here, we investigated the impact of non-amyloidogenic rodent IAPP (rIAPP) on GABA _<i>A</i> receptor-mediated neuronal inhibition in mouse dorsal and ventral hippocampal dentate gyrus (DG) granule cells. Using whole-cell patch-clamp recordings, we showed that rIAPP selectively enhanced both GABA-activated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in ventral, but not dorsal, hippocampal DG granule cells. The effect of rIAPP on sIPSCs was completely abolished in the presence of the amylin receptor antagonist IAPP_8-37. Interestingly, GABA _<i>A</i> receptor-mediated tonic current density remained unchanged in either dorsal or ventral hippocampal DG granule cells during rIAPP application. This region-specific and inhibition type-specific effect of rIAPP is likely associated with differential modulation of presynaptic GABA release as well as postsynaptic GABA _<i>A</i> receptors in the ventral as compared to the dorsal hippocampus. Our results suggest that rodent IAPP acts as a neuromodulator in hippocampal subregions by altering the strength of GABA _<i>A</i> receptor-mediated inhibitory signaling.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1531790"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566660","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":"Multiscale brain modeling: bridging microscopic and macroscopic brain dynamics for clinical and technological applications.","authors":"Ondrej Krejcar, Hamidreza Namazi","doi":"10.3389/fncel.2025.1537462","DOIUrl":"10.3389/fncel.2025.1537462","url":null,"abstract":"<p><p>The brain's complex organization spans from molecular-level processes within neurons to large-scale networks, making it essential to understand this multiscale structure to uncover brain functions and address neurological disorders. Multiscale brain modeling has emerged as a transformative approach, integrating computational models, advanced imaging, and big data to bridge these levels of organization. This review explores the challenges and opportunities in linking microscopic phenomena to macroscopic brain functions, emphasizing the methodologies driving progress in the field. It also highlights the clinical potential of multiscale models, including their role in advancing artificial intelligence (AI) applications and improving healthcare technologies. By examining current research and proposing future directions for interdisciplinary collaboration, this work demonstrates how multiscale brain modeling can revolutionize both scientific understanding and clinical practice.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1537462"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566655","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":"Profiling gene alterations in striatonigral neurons associated with incubation of methamphetamine craving by cholera toxin subunit B-based fluorescence-activated cell sorting.","authors":"Rachel D Altshuler, Megan A M Burke, Kristine T Garcia, Kenneth Class, Raffaello Cimbro, Xuan Li","doi":"10.3389/fncel.2025.1542508","DOIUrl":"10.3389/fncel.2025.1542508","url":null,"abstract":"<p><strong>Introduction: </strong>In both rats and humans, methamphetamine (Meth) seeking progressively increases during abstinence, a behavioral phenomenon termed \"incubation of Meth craving\". We previously demonstrated a critical role of dorsal striatum (DS) in this incubation in rats. However, circuit-specific molecular mechanisms in DS underlying this incubation are largely unknown. Here we combined a newly developed fluorescence-activated sorting (FACS) protocol with fluorescence-conjugated cholera toxin subunit B-647 (CTb-647, a retrograde tracer) to examine gene alterations in the direct-pathway (striatonigral) medium spiny neurons (MSNs) associated with incubation of Meth craving.</p><p><strong>Methods: </strong>We injected CTb-647 bilaterally into substantia nigra before or after training rats to self-administer Meth or saline (control condition) for 10 days (6 h/d). On abstinence day 1 or day 28, we collected the DS tissue from both groups for subsequent FACS and examined gene expressions in CTb-positive (striatonigral MSNs) and CTb-negative (primarily non-striatonigral MSNs). Finally, we examined gene expressions in DS homogenates, to demonstrate cell-type specificity of gene alterations observed on abstinence day 28.</p><p><strong>Results: </strong>On abstinence day 1, we found mRNA expression of <i>Gabrb3</i> decreased only in CTb-positive (but not CTb-negative) neurons of Meth rats compared with saline rats, while mRNA expression of <i>Usp7</i> decreased in all sorted DS neurons. On abstinence day 28, we found increased mRNA expression for <i>Grm3, Opcml</i>, and <i>Usp9x</i> in all sorted DS neurons, but not DS homogenate.</p><p><strong>Discussion: </strong>Together, these data demonstrated that incubation of Meth craving was associated with time-dependent, circuit-specific, and cell type-specific gene alterations in DS involved in glutamatergic, GABAergic, opioidergic, and protein degradation signaling.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1542508"},"PeriodicalIF":4.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515106","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":"Direct effects of prolonged TNF-α and IL-6 exposure on neural activity in human iPSC-derived neuron-astrocyte co-cultures.","authors":"Noah Goshi, Doris Lam, Chandrakumar Bogguri, Vivek Kurien George, Aimy Sebastian, Jose Cadena, Nicole F Leon, Nicholas R Hum, Dina R Weilhammer, Nicholas O Fischer, Heather A Enright","doi":"10.3389/fncel.2025.1512591","DOIUrl":"10.3389/fncel.2025.1512591","url":null,"abstract":"<p><p>Cognitive impairment is one of the many symptoms reported by individuals suffering from long-COVID and other post-viral infection disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A common factor among these conditions is a sustained immune response and increased levels of inflammatory cytokines. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are two such cytokines that are elevated in patients diagnosed with long-COVID and ME/CFS. In this study, we characterized the changes in neural functionality, secreted cytokine profiles, and gene expression in co-cultures of human iPSC-derived neurons and primary astrocytes in response to prolonged exposure to TNF-α and IL-6. We found that exposure to TNF-α produced both a concentration-independent and concentration-dependent response in neural activity. Burst duration was significantly reduced within a few days of exposure regardless of concentration (1 pg/mL - 100 ng/mL) but returned to baseline after 7 days. Treatment with low concentrations of TNF-α (e.g., 1 and 25 pg/mL) did not lead to changes in the secreted cytokine profile or gene expression but still resulted in significant changes to electrophysiological features such as interspike interval and burst duration. Conversely, treatment with high concentrations of TNF-α (e.g., 10 and 100 ng/mL) led to reduced spiking activity, which may be correlated to changes in neural health, gene expression, and increases in inflammatory cytokine secretion (e.g., IL-1β, IL-4, and CXCL-10) that were observed at higher TNF-α concentrations. Prolonged exposure to IL-6 led to changes in bursting features, with significant reduction in the number of spikes in bursts across a wide range of treatment concentrations (i.e., 1 pg/mL-10 ng/mL). In combination, the addition of IL-6 appears to counteract the changes to neural function induced by low concentrations of TNF-α, while at high concentrations of TNF-α the addition of IL-6 had little to no effect. Conversely, the changes to electrophysiological features induced by IL-6 were lost when the cultures were co-stimulated with TNF-α regardless of the concentration, suggesting that TNF-α may play a more pronounced role in altering neural function. These results indicate that increased concentrations of key inflammatory cytokines associated with long-COVID can directly impact neural function and may be a component of the cognitive impairment associated with long-COVID and other post-viral infection disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1512591"},"PeriodicalIF":4.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515163","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":"Glymphatic system: a self-purification circulation in brain.","authors":"Siying Chen, Huijing Wang, Lini Zhang, Yingying Xi, Yiying Lu, Kailin Yu, Yujie Zhu, Izmailova Regina, Yong Bi, Fang Tong","doi":"10.3389/fncel.2025.1528995","DOIUrl":"10.3389/fncel.2025.1528995","url":null,"abstract":"<p><p>The glymphatic system theory introduces a new perspective on fluid flow and homeostasis in the brain. Here, cerebrospinal fluid and interstitial fluid (CSF-ISF) moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) plays a crucial role in driving fluid within the PVS. The impairment to AQP4 is closely linked to the dysfunction of the glymphatic system. The function of the glymphatic system is less active during waking but enhanced during sleep. The efficiency of the glymphatic system decreases with aging. Damage to the glymphatic system will give rise to the development and progression of many brain diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and vascular dementia (VaD). Here, we reviewed previous research associated with the glymphatic system, including its concepts, principles, and influencing factors. We hypothesize that AQP4 could be a target for the prevention and treatment of certain brain diseases through the regulation on the glymphatic system.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1528995"},"PeriodicalIF":4.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514949","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: Cellular and molecular mechanisms that govern assembly, plasticity, and function of GABAergic inhibitory circuits in the mammalian brain.","authors":"Yasufumi Hayano, Goichi Miyoshi, Anirban Paul, Hiroki Taniguchi","doi":"10.3389/fncel.2025.1568845","DOIUrl":"10.3389/fncel.2025.1568845","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1568845"},"PeriodicalIF":4.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498941","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}