Frontiers in Cellular Neuroscience最新文献

{"title":"Stress-responsive nucleus accumbens dopamine D2 receptor-expressing neurons modulate cocaine-induced behavioral sensitization.","authors":"Byeong Jun Kang, Bokyeong Kim, Minji Kim, Yoonsoo Choi, Eum-Ji Kim, Ja Wook Koo, Ja-Hyun Baik","doi":"10.3389/fncel.2026.1919290","DOIUrl":"10.3389/fncel.2026.1919290","url":null,"abstract":"<p><p>Although both stress and cocaine induce robust plasticity within the nucleus accumbens core (NAcc), how these distinct experiences interact at the cellular level to shape behavior remains unclear. Here, we investigated the role of NAcc dopamine D2 receptor-expressing medium spiny neurons (D2R-MSNs) in integrating stress- and drug-induced signals. D2R-MSNs showed distinct activity responses, with increased activity during restraint stress and reduced activity following repeated cocaine exposure. Using the Cre-dependent Robust Activity Marking (cRAM) system, we found that cocaine exposure suppressed the activity of the subpopulation of D2R-MSNs previously recruited by stress. Optogenetic reactivation of these stress-tagged D2R-MSNs during withdrawal attenuated the expression of cocaine-induced behavioral sensitization. Transcriptomic profiling of stress-responsive D2R-MSNs identified cholecystokinin (<i>Cck</i>) as a candidate associated with this neuronal manipulation. Subsequent experiments showed that cocaine exposure increased CCK expression in NAcc D2R-MSNs, whereas conditional Cck knockdown reduced the expression of behavioral sensitization. Together, these findings suggest that stress-responsive D2R-MSNs contribute to the regulation of cocaine-induced behavioral sensitization and that CCK signaling within NAcc D2R-MSNs may be involved in this process.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1919290"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826810","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":"Unmasking a neurotoxic duo: a comprehensive overview of fentanyl-xylazine crosstalk in kinase pathways.","authors":"Sally N Pauss, Zachary A Kipp, Cassandra D Gipson, Terry D Hinds","doi":"10.3389/fncel.2026.1851956","DOIUrl":"10.3389/fncel.2026.1851956","url":null,"abstract":"<p><strong>Introduction: </strong>Fentanyl is the main cause of the US overdose crisis, responsible for over half of overdose deaths, totaling around 75,000 lives each year. The contamination of the illegal drug supply with xylazine has been linked to an increase in overdose fatalities. Adding xylazine to fentanyl causes additional health issues, including tissue necrosis, more severe withdrawal symptoms, and higher overdose lethality, while also potentially reducing the effectiveness of naloxone. Therefore, understanding the molecular signaling events when fentanyl is combined with xylazine is crucial.</p><p><strong>Methods: </strong>In these experiments, we treated the human neuronal cell line SH-SY5Y with fentanyl and xylazine and conducted detailed analyses using the PamGene PamStation to measure kinase activities across over 500 pathways, thereby stratifying and identifying affected signaling pathways.</p><p><strong>Results: </strong>Our results show that fentanyl and xylazine impact kinase activity differently when either is used alone, and often, xylazine diminishes the kinase activity changes caused by fentanyl alone. We also found that the combination of these drugs uniquely increases the phosphorylation of diverse substrates compared with each drug alone.</p><p><strong>Discussion: </strong>These are the first kinome analyses performed on human cells with fentanyl and xylazine, which may uncover new therapeutic targets to counteract their harmful combined effects.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1851956"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826837","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: 15 years of Frontiers in Cellular Neuroscience: exploring astrocyte heterogeneity: regional functions and impacts on diseases.","authors":"Carmen Falcone, Francesco Petrelli","doi":"10.3389/fncel.2026.1951315","DOIUrl":"https://doi.org/10.3389/fncel.2026.1951315","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1951315"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818055","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":"Correction: 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.","authors":"Shan Jiang, Eric J Sydney, Avery M Runyan, Rossana Serpe, Malavika Srikanth, Helen Y Figueroa, Mu Yang, Natura Myeku","doi":"10.3389/fncel.2026.1945844","DOIUrl":"https://doi.org/10.3389/fncel.2026.1945844","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2024.1338502.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1945844"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818079","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>GRIA3</i>: proposal for a neuroimmune role linking infection, stress, chronic disorders and the activity of kynurenic acid.","authors":"Trevor W Stone, Felix I L Clanchy, Richard O Williams","doi":"10.3389/fncel.2026.1885761","DOIUrl":"10.3389/fncel.2026.1885761","url":null,"abstract":"<p><p>Glutamate receptors in the CNS sensitive to the analog AMPA regulate neuronal excitability and synaptic plasticity. AMPA receptors are usually hetero-tetramers and the human <i>GRIA3</i> gene and GluA3 protein product have been implicated in various CNS abnormalities including epilepsy, multiple sclerosis, schizophrenia, and cognitive disorders. Although not generally found in the immune system, <i>GRIA3</i> has recently been demonstrated in a highly specialized group of immune system cells-plasmacytoid dendritic cells (pDCs). These are among the first cells to be activated by infecting viruses and they express <i>GRIA3</i> in the absence of other AMPA receptor subunits, suggesting a possible role for the subunit in those neuroimmune disorders. The potential for molecular interactions between pDCs and neurons or glia is discussed, with the implications for linking viral infections, pDC activation, and chronic diseases. With growing evidence that the tryptophan metabolite kynurenic acid-an AMPA antagonist-is involved with a similar range of disorders, its role in those links is also discussed.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1885761"},"PeriodicalIF":4.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812470","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":"Mitochondrial dysfunction in intracerebral hemorrhage: molecular mechanisms and pathological consequences.","authors":"Tong Chen, Xu Gao, Yuhao Chang, Bin Wang, Zhouying Shi, Haiyue Xu, Yue Yuan, Fan Li, Ping Li","doi":"10.3389/fncel.2026.1913984","DOIUrl":"https://doi.org/10.3389/fncel.2026.1913984","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) carries high rates of disability and mortality, with a poor prognosis largely attributable to secondary brain injury (SBI). Mitochondria, a central hub for cellular redox regulation and energy metabolism, are not only affected by SBI but can also, once dysfunctional, initiate and exacerbate SBI. In this review, we classify post-ICH mitochondrial dysfunction into three major categories: excessive accumulation of mitochondrial reactive oxygen species, dysregulation of energy metabolism, and dysregulation of mitochondrial quantity and quality control. We delineate the molecular mechanisms and pathological consequences of each. Furthermore, given the extensive crosstalk between mitochondrial dysfunction and diverse forms of cell death in ICH (e.g., apoptosis, necrosis, necroptosis, ferroptosis, and pyroptosis), we discuss their mechanistic links. Overall, this review proposes a mitochondria-centered framework and emphasizes crosstalk between different types of dysfunction, thereby advancing our understanding of SBI pathophysiology after ICH and providing a systematic perspective on therapeutic strategies aimed at restoring mitochondrial homeostasis.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1913984"},"PeriodicalIF":4.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790246","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 identification of white matter fibers in the hematoma of intracerebral hemorrhage patients.","authors":"Jianan Wu, Cheng Zhang, Xian Yu, Huaijun Chen, Haopu Lin, Qizhen He, Chenjun Sun, Guangyu Ying, Feng Cai, Jiaming Xu, Jingsen Chen, Chi Gu, Gao Chen, Jingyin Chen","doi":"10.3389/fncel.2026.1816722","DOIUrl":"https://doi.org/10.3389/fncel.2026.1816722","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) carries high mortality, and survivors often have severe neurological deficits. Although surgical clot evacuation is widely used, clinical trials have not demonstrated a clear benefit. White matter is essential for neural network function and may be vulnerable during hematoma evacuation, but whether white matter fibers exist within human ICH hematomas remains unknown. This study aimed to determine the presence and characteristics of intra-hematomal white matter fibers and their relationship with immune cell infiltration.</p><p><strong>Methods: </strong>We collected hematoma specimens from patients with spontaneous supratentorial ICH undergoing surgical evacuation within 24 h of onset. Histological and immunohistochemical staining, including hematoxylin-eosin and myelin basic protein (MBP), was performed to identify white matter fibers. Lymphatic vessel hyaluronan receptor-1 (LYVE-1) staining was used to evaluate macrophage infiltration around identified fibers.</p><p><strong>Results: </strong>Myelin-containing structures were consistently observed within the hematoma core on both hematoxylin-eosin and MBP staining. These structures appeared fragmented and structurally fragile. LYVE-1-positive cells were found clustered around intra-hematomal myelin-containing structures, potentially indicating active immune cell infiltration in these regions.</p><p><strong>Conclusion: </strong>This study provides the first direct histological evidence that white matter fibers persist within human ICH hematomas. This finding provides an anatomical basis for future studies exploring the biological and potential clinical significance of intra-hematomal white matter-associated structures.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1816722"},"PeriodicalIF":4.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790290","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":"Characterization of TRPV2-associated pathology in Parkinson's disease and therapeutic modulation using Tranilast.","authors":"Apeksha Chunchuwar, Bhupesh Vaidya, Shyam Sunder Sharma","doi":"10.3389/fncel.2026.1896592","DOIUrl":"https://doi.org/10.3389/fncel.2026.1896592","url":null,"abstract":"<p><strong>Introduction: </strong>Transient Receptor Potential (TRP) channels have gained worldwide attention for their expression and distribution in multiple human organs. Among these TRPs, Transient Receptor Potential Vanilloid (TRPV) channels play diverse physiological roles in the brain, and changes in their expression contribute to central nervous system (CNS) diseases. In a previous druggable-genome α-synuclein modifier screen, a member of the TRPV family, TRPV2, emerged as a Tier 3 ion-channel candidate, meeting directionality and conflict-score criteria, though with limited shRNA-level support. However, based on this preliminary data and the known role of TRPV2 in Ca²⁺ entry and cellular stress responses, we decided to investigate its role in detail using experimental PD models.</p><p><strong>Methods: </strong>In the present investigation, 6-hydroxydopamine (6-OHDA) was used <i>in vivo</i> (Sprague Dawley rats) and <i>in vitro</i> (SH-SY5Y cells) to induce Parkinson's disease (PD), and its effect on TRPV2 expression was investigated. The study further involved measuring behavioral parameters using the rotarod, open field, apomorphine, and cylinder tests.</p><p><strong>Results: </strong>6-OHDA administration induced excessive reactive oxygen species (ROS) production and increased expression of TRPV2 channels. This is also accompanied by increased intracellular calcium influx and reduces cell viability. However, Tranilast, a TRPV2 antagonist, exhibited promising neuroprotective effects in the 6-OHDA PD model by restoring tyrosine hydroxylase levels, reducing oxidative stress, and improving motor function. Also, it diminished the intracellular Ca²⁺ influx and reduced ROS levels in the 6-OHDA-treated SH-SY5Y cells.</p><p><strong>Conclusion: </strong>Overall, our results suggest that TRPV2 levels are elevated in PD, and targeting TRPV2 could be a potential therapeutic approach in the future.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1896592"},"PeriodicalIF":4.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790318","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":"Adolescent stress exposure: behavioral consequences and molecular mechanisms in corticolimbic networks.","authors":"Evelin M Cotella, Rachel D Moloney, Parinaz Mahbod, Susan Martelle, Rachel L Morano, Benjamin A Packard, James P Herman","doi":"10.3389/fncel.2026.1876565","DOIUrl":"10.3389/fncel.2026.1876565","url":null,"abstract":"<p><strong>Introduction: </strong>Adolescence is a sensitive developmental period during which chronic stress can induce lasting adaptations in corticolimbic circuits involved in stress regulation, cognition, and emotional behavior. We examined the long-term behavioral, endocrine, and molecular consequences of adolescent chronic variable stress (CVS) in male and female rats, focusing on the infralimbic cortex (IL) and basolateral amygdala (BLA).</p><p><strong>Methods: </strong>Sprague Dawley rats of both sexes were exposed to CVS during late adolescence and evaluated in adulthood after an extensive recovery period. Behavioral testing included cued fear conditioning and extinction recall, delayed spatial win-shift, novel object recognition, Morris water maze, three-chamber social behavior, and passive avoidance. HPA-axis reactivity to acute restraint was assessed. Targeted qPCR was used to measure stress-related gene expression in the IL and BLA immediately after stress or after a 5-week recovery period.</p><p><strong>Results: </strong>Adolescent CVS did not cause generalized cognitive impairment, but instead produced selective, sex-specific effects. Females had reduced HPA responses to acute stress and mild deficits in delayed spatial win-shift performance, together with long-term IL changes in genes related to adrenergic signaling, plasticity, and GABA clearance. Males showed enhanced Morris water maze probe retention, weaker novel object discrimination, altered passive avoidance with marked inter-individual variability, and enhanced social preference. At the molecular level, males exhibited long-term upregulation of Fkbp5 in IL and downregulation of PACAP, α1D adrenergic receptor, and proenkephalin in BLA, whereas females showed delayed PACAP upregulation in BLA.</p><p><strong>Discussion: </strong>Adolescent CVS induces persistent, sex- and region-specific recalibration of corticolimbic function, supporting distinct patterns of vulnerability and resilience, rather than uniform stress pathology.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1876565"},"PeriodicalIF":4.4,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790309","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 rhythms of neuronal and astrocytic glutamate transporters in the suprachiasmatic nucleus of mice.","authors":"Hussein Haidar, Amira A H Ali, Charlotte von Gall, Federica Tundo-Lavalle","doi":"10.3389/fncel.2026.1875844","DOIUrl":"https://doi.org/10.3389/fncel.2026.1875844","url":null,"abstract":"<p><p>Retinal ganglion cells release glutamate at their synapses, transmitting visual signals via the optic nerve to brain regions involved in vision and light-dependent functions. Glutamatergic input to the circadian pacemaker, the suprachiasmatic nucleus (SCN), is essential for photoentrainment of circadian rhythms. Glutamate transporters are crucial for efficient transmission in the tripartite synapse formed by presynaptic terminals, postsynaptic neurons and astrocytes. However, it remains unclear whether this glutamatergic synapse is modulated by rhythmic environmental lighting conditions. In this study, neuronal (VGLUT1 and VGLUT2) and astrocytic (GLAST) glutamate transporters of 8-12 weeks old male C57Bl/6 J mice were analyzed in the SCN of mice exposed to different lighting paradigms: a standard 12:12-h light-dark cycle (LD), constant darkness (DD) and constant light (LL), using immunofluorescence and confocal laser microscopy. Under LD, all three transporters exhibited time-of-day-dependent rhythms: VGLUT1 and GLAST peaked during the light phase, while VGLUT2 peaked during the dark phase. This suggests that VGLUT1 and GLAST are more strongly coupled and that VGLUT2 is a complementary system, so that the strength or efficiency of the light information can be modulated depending on the time of day. Furthermore, the rhythms of neuronal glutamate transporters persisted under DD and LL, indicating robust circadian control. Our study thus supports the hypothesis that the circadian system may regulate its own input.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1875844"},"PeriodicalIF":4.4,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790314","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}