Frontiers in Cellular Neuroscience最新文献

{"title":"CaMKII modulates memory destabilization by regulating the interaction of theta and gamma oscillations.","authors":"Janine I Rossato, Maria Carolina Gonzalez, Johseph P G Souza, Andressa Radiske, Gênedy Apolinario, Ana Luizi Baracho, Martín Cammarota","doi":"10.3389/fncel.2025.1620588","DOIUrl":"10.3389/fncel.2025.1620588","url":null,"abstract":"<p><p>Object recognition memory (ORM) allows animals to distinguish between novel and familiar items. When reactivated during recall in the presence of a novel object, a consolidated ORM can be destabilized and linked to that generated by the novel object through reconsolidation. The CA1 region of the dorsal hippocampus contributes to ORM destabilization and reconsolidation, with mechanisms involving theta/gamma cross-frequency coupling (hPAC) and synaptic plasticity modulation. Ca²+/calmodulin-dependent protein kinase II (CaMKII) is vital for hippocampus-dependent memory processing and has been associated with theta activity-dependent plasticity in dorsal CA1. However, the specific role of hippocampal CaMKII in the lasting storage of reactivated ORM remains unclear, and its potential impact on memory-related oscillatory activity has not been previously investigated. To explore these questions, we employed a combination of behavioral, electrophysiological, and pharmacological approaches at various stages of ORM processing, and found that CaMKII is not necessary for ORM recall or reconsolidation but does regulate novelty-induced ORM destabilization by modulating hPAC.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1620588"},"PeriodicalIF":4.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014350","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":"Buffering brain aging: education moderates language impairment in Parkinson's disease.","authors":"Minchul Kim, Kwangsun Yoo","doi":"10.3389/fncel.2025.1606451","DOIUrl":"10.3389/fncel.2025.1606451","url":null,"abstract":"<p><strong>Background: </strong>Cognitive reserve (CR) refers to the discrepancy between brain pathology and observed cognitive decline. While education is a key indicator of CR, its role as a potential moderator in the relationships between brain morphology and cognitive impairments in Parkinson's disease (PD) remains unclear. This study examined whether education affects the relationship between brain age and cognitive impairments in patients with PD.</p><p><strong>Methods: </strong>Data from 58 patients with PD were analyzed using a secondary dataset from the OpenNeuro database. Participants aged ≥55 years were on stable medications and underwent standardized neuropsychological assessments. Brain age predictions were generated from T1-weighted magnetic resonance imaging (MRI) using the brainageR package, and the brain age difference (BAD) was calculated after correction for regression dilution. The moderation effect of education on the relationship between BAD and cognition was assessed using Hayes' PROCESS macro. The primary outcome was cognitive performance across six domains: attention, executive function, language, learning and memory, visuospatial ability, and global cognition.</p><p><strong>Results: </strong>Among the six domains, a significant moderation effect of education was found only for language ability (β = 0.01, <i>p</i> = 0.013, <i>R</i> ² = 0.20). The relationship between BAD and language was steeper at lower education levels. No statistically significant moderation was found in the remaining five domains.</p><p><strong>Conclusion: </strong>Having more years of education is associated with buffering the effects of accelerated brain aging on language ability in PD.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1606451"},"PeriodicalIF":4.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12405238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000184","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":"Neuroprotective effects of saikosaponin-A in ethanol-induced glia-mediated neuroinflammation, oxidative stress via RAGE/TLR4/NFkB signaling.","authors":"Waqar Ali, Kyonghwan Choe, Min Hwa Kang, Jawad Ali, Hyun Young Park, Abubakar Atiq, Sareer Ahmad, Tae Ju Park, Myeong Ok Kim","doi":"10.3389/fncel.2025.1625362","DOIUrl":"10.3389/fncel.2025.1625362","url":null,"abstract":"<p><p>Chronic use of ethanol leads to psychological and physiological dependence followed by neurodegeneration via glia-mediated neuroinflammation, and oxidative stress. The current study is aimed at the neuroprotective effects of saikosaponin-A against ethanol-induced neurodegeneration. Here, saikosaponin-A 10 mg/kg i.p., for 7 days was used against the ethanol (5 g/kg i.p., for 6 weeks) induced neuroinflammation via RAGE/TLR4 signaling in mouse neurodegenerative model. The immunoblotting and immunofluorescences microscopy results showed that, ethanol activates the glial cells at the level of mice brain. The relative expression of Toll like receptor (TLR4), receptor for advance glycation end product (RAGE), ionized calcium binding adaptor molecules 1 (Iba-1), glial fibrillary acidic protein (GFAP) was upregulated in ethanol-treated mice group. However, expression level of inflammatory biomarkers were downregulated in ethanol + SSA co-treated group. Similarly, our finding revealed that SSA significantly reduced the protein expression level of Phospo c-Jun N-Terminal Kinase (p-JNK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and downstream signaling targets in ethanol + SSA co-treated group. SSA also regulates the elevated ethanol-induced oxidative stress via NRF2 and HO-1 proteins. Finally, we analyzed the synaptic and behavioral alteration that was reversed in SSA treated group. Taken together, we concluded that SSA exhibits anti-inflammatory and antioxidant effects against ethanol-induced neurodegeneration.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1625362"},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991825","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":"Attention-deficit hyperactivity disorder in spontaneously hypertensive rat strain SHR/NCrl is associated with specific expression of uncoupling proteins, glucose transporter 1 and BACE1.","authors":"Tsunehisa Sato, Rolf Schreckenberg, Klaus-Dieter Schlüter","doi":"10.3389/fncel.2025.1612751","DOIUrl":"10.3389/fncel.2025.1612751","url":null,"abstract":"<p><p>Attention-deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder worldwide. To improve treatment strategies against ADHD a better understanding of underlying pathophysiology is required. Spontaneously hypertensive rats (SHR) from the strain SHR/NCrl are a suitable rodent model of ADHD. Here we compared the gene expression in the brains of SHR/NCrl strain to that of other genetically related hypertensive and normotensive rat strains that do not show an ADHD phenotype. In addition, the impact of physical activity on genes that display such differences was also addressed because high physical activity is one non-pharmacological option to cure ADHD symptoms. RNA was isolated from the medulla oblongata, the olfactory bulb, and the cortex. Gene expression was analyzed by qRT-PCR. The cortical expression of GLUT1 was also analyzed by Western Blot. Physical activity was improved by free access to running wheels for six months. Female rats were used in this study and sacrificed at the age of 7.5 months. The results show that gene expression in SHR/NCrl differs from other SHR strains in the olfactory bulb, medulla oblongata, and the cortex. Main differences were obtained for <i>SLC25A14</i>, coding for the protein UCP5, <i>SLC2A1</i>, coding for the protein glucose transporter (GLUT) 1 in the cortex and <i>CCL2</i> and for <i>BACE1</i> in the medulla oblongata. The expressions of <i>SLC25A14</i> and <i>BACE1</i> in the medulla oblongata were normalized in physical active rats. Our study further underlines the usefulness of the SHR/NCrl strain as an ADHD animal model when combined with proper controls. Furthermore, this study identifies genes that are specifically down-regulated in the medulla oblongata of SHR/NCrl and that are affected by activity status.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1612751"},"PeriodicalIF":4.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991847","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":"SFXN2 contributes mitochondrial dysfunction-induced apoptosis as a substrate of Parkin.","authors":"Shishi Luo, Yechuan He, Yaohui He, Danling Wang","doi":"10.3389/fncel.2025.1623747","DOIUrl":"10.3389/fncel.2025.1623747","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondria, situated at the center of intricate signaling networks, play crucial roles in maintaining health and driving disease progression. SFXN2, a recently identified member of the mitochondrial transporter family, is localized to the outer mitochondrial membrane and regulates several critical mitochondrial functions, including iron metabolism, heme biosynthesis, bioenergetics, and redox homeostasis. New evidence also suggests a connection between SFXN2 and mitochondrial dysfunction related human diseases such as Parkinson's disease (PD). Despite growing insights into SFXN2's roles across various mitochondrial functions, its regulation under mitochondrial dysfunction and the resulting biological consequences remains unclear.</p><p><strong>Methods: </strong>The expression levels of SFXN2 protein were analyzed by Western blotting WB. The interaction between SFXN2 and Parkin was examined using co-immunoprecipitation and immunofluorescence assays. Furthermore, the effect of Parkin on SFXN2 ubiquitination was assessed via ubiquitination assay. Finally, RNA sequencing and flow cytometry were employed to investigate that SFXN2 regulates the apoptotic pathway.</p><p><strong>Results: </strong>In this study, we identify SFXN2 as a key regulator of mitochondrial homeostasis, demonstrating that its level is tightly regulated via Parkin-mediated ubiquitination and proteasomal degradation. Under conditions of mitochondrial damage, Parkin enhances the degradation of SFXN2, and the reduction of SFXN2 contributes to apoptotic cell death. Functional studies across multiple cell lines, including HEK293, SH-SY5Y, and N2a cells, reveal that the reduction of SFXN2 exacerbates mitochondrial damage-induced apoptosis, whereas overexpression of SFXN2 exhibits an anti apoptotic effect.</p><p><strong>Discussion: </strong>Our findings offer new insights into the regulation of SFXN2 in mitochondrial dysfunction through Parkin mediated ubiquitin proteasome system activity, underscoring SFXN2's potential implications in nerodegenerative diseases, particularly PD.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1623747"},"PeriodicalIF":4.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948737","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":"Underestimation of mitochondrial respiratory capacity in gray matter voxels of the human brain map due to limited OXPHOS and TCA cycle in astrocytes.","authors":"Christos Chinopoulos","doi":"10.3389/fncel.2025.1661231","DOIUrl":"10.3389/fncel.2025.1661231","url":null,"abstract":"<p><p>Considering that the aerobic energetic landscape of the brain is shaped by its mitochondria, Mosharov et al. generated an atlas of mitochondrial content and enzymatic OXPHOS activities at a resolution comparable to MRI by physically voxelizing frozen human brain tissue. However, astrocytes in the adult human brain lack expression of several TCA cycle and OXPHOS enzymes. Therefore, their formula expressing mitochondrial respiratory capacity (MRC) -defined as tissue respiratory capacity normalized to mitochondrial density- underestimates actual values by a factor proportional to the square root of the fraction of respiration-capable cells (primarily neurons) in gray matter voxels.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1661231"},"PeriodicalIF":4.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948794","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":"Potential impacts of acupuncture on motor function recovery after ischemic stroke: insights from basic and clinical studies.","authors":"Jia-Ling He, Liang-Xiao Ma, Jing-Si Wen, Yu-Xin Zhuang, Xu Qian, Ling-Hui Ma, Jing-Yun Xiu, Xiu-Yan Wang, Meng-Yu Chen","doi":"10.3389/fncel.2025.1623535","DOIUrl":"10.3389/fncel.2025.1623535","url":null,"abstract":"<p><p>Ischemic stroke is one of the leading causes of death and long-term disability worldwide. A significant proportion of stroke survivors experience persistent motor impairments, which severely affect their quality of life and cause heavy social and economic burdens. Acupuncture has increasingly gained attention due to its remarkable efficacy in promoting motor function recovery after stroke, and it has been progressively endorsed as a post-stroke treatment option by clinical guidelines of numerous countries, despite its underlying mechanism is not yet fully understood. This review systematically evaluates existing basic and clinical studies to explore the potential mechanisms of acupuncture's effects on motor function recovery after ischemic stroke and the optimal clinical strategies. Emerging evidence demonstrates that acupuncture-mediated post-stroke motor recovery is primarily attributed to its roles in restoring energy metabolism, inhibiting neuroinflammation, preventing neuronal apoptosis, promoting neuronal repair and regeneration, and regulating neuronal excitability. Additionally, individualized acupuncture modality involving syndrome-based selection of acupoints and stimulating methods is crucial for better rehabilitation outcome. Our findings elucidate the multidimensional impacts of acupuncture on motor function restoration following ischemic stroke, furnishing robust evidence and theoretical foundation for its clinical application.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1623535"},"PeriodicalIF":4.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948718","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":"NMDAR inhibitor preconditioned mesenchymal stromal cell-derived extracellular vesicles enhance post-stroke recovery by targeting excitotoxicity and neuronal regeneration.","authors":"XiaoLu Zhang, HuanNa Tian, HaiMei Bo, Li Zhong","doi":"10.3389/fncel.2025.1608615","DOIUrl":"10.3389/fncel.2025.1608615","url":null,"abstract":"<p><strong>Background: </strong>Stroke is a leading global cause of disability and mortality, with ischemic stroke triggering NMDAR overactivation and excitotoxic neuronal injury. Extracellular vesicles (EVs) derived from stem cells under specific microenvironmental conditions show therapeutic potential for stroke recovery.</p><p><strong>Materials and methods: </strong>Photothrombotic stroke was induced in male ICR mice, followed by intravenous administration of EVs from memantine-preconditioned human umbilical cord mesenchymal stem cells (HUC-MSCs; M-EV). Behavioral outcomes were assessed using modified neurological severity scores (mNSS) and Morris water maze tests. Tissue damage was evaluated via TTC staining, Evans blue extravasation, and immunofluorescence. PCR-array analysis identified neuronal regeneration pathways. In vitro, oxygen-glucose deprivation (OGD)-challenged HT22 hippocampal neurons were co-cultured with M-EV to assess viability, migration, and apoptosis.</p><p><strong>Results: </strong>M-EV outperformed conventional EVs in functional recovery, with miR-139-5p and miR-133b identified as key miRNAs enriched in M-EV, mediating neuroprotective effects. M-EV treatment activated neuronal regeneration pathways and reduced infarct volume. In OGD models, M-EV enhanced HT22 neuron viability, promoted migration, and suppressed apoptosis.</p><p><strong>Conclusion: </strong>Memantine-preconditioned EVs (M-EVs) exhibit superior neurorestorative capacity via miRNA-mediated mechanisms, offering a promising translational approach for stroke therapy. The study highlights the potential of microenvironment-tailored EVs in neural repair.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1608615"},"PeriodicalIF":4.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948703","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":"Cell-type specific repertoire of responses to natural scenes in primate retinal ganglion cells.","authors":"Alexandra Kling, Nora Brackbill, Colleen Rhoades, Alex Gogliettino, Alexander Sher, Alan Litke, E J Chichilnisky","doi":"10.3389/fncel.2025.1600167","DOIUrl":"10.3389/fncel.2025.1600167","url":null,"abstract":"<p><p>At least 20 distinct retinal ganglion cell (RGC) types have been identified morphologically in the primate retina, but our understanding of the distinctive visual messages they send to various targets in the brain remains limited, particularly for naturalistic stimuli. Here, we use large-scale multi-electrode recordings to examine how multiple functionally distinct RGC types in the macaque retina respond to flashed natural images. Responses to white noise visual stimulation were used to functionally identify 936 RGCs of 12 types in three recordings. Each cell type was confirmed by the mosaic organization of receptive fields, and seven cell types were cross-identified between recordings. Responses to thousands of natural images were used to examine the average firing rate kinetics in each RGC type as well as the repertoire of distinct firing patterns that each type produced. The average response across images was highly stereotyped for cells of each type and distinct for cells of different types. The responses to natural images more clearly distinguished certain cell types than did the response to white noise stimulation. Moreover, the full repertoires of firing patterns produced by different cell types, assessed by their latency and duration, were largely distinct in most cases and in some cases non-overlapping. Together these data provide an overview of the diversity of RGC signals transmitted from the primate retina to the brain in natural viewing conditions.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1600167"},"PeriodicalIF":4.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948766","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":"Decreased neuronal and increased endothelial fractalkine expression are associated with neuroinflammation in Parkinson's disease and related disorders.","authors":"Yaping Chu, Ashley S Harms, Ashley Boehringer, Jeffrey H Kordower","doi":"10.3389/fncel.2025.1557645","DOIUrl":"10.3389/fncel.2025.1557645","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic neuroinflammation is a persistent feature of individuals with Parkinson's disease (PD). Dopaminergic neurodegeneration is partially associated with neuroinflammation. Neuron-to-microglia communication via fractalkine (CX3CL1) and its receptor plays a significant role in neuroinflammation. The relationship between fractalkine signaling and neuroinflammatory activities has been studied in animal models of PD, but its role is unclear in human PD. The current study aimed to elucidate the neuron-microglia communication between neuronal and endothelial fractalkine ligand expression, microglial activity, and CD4⁺ T cell infiltration during PD development.</p><p><strong>Methods: </strong>Brain sections were obtained from age-matched control subjects with no motor deficits (control, <i>n</i> = 8), mild motor deficits with nigral Lewy bodies (MMD-LB, <i>n</i> = 8) without a clinical diagnosis of PD, individuals with a clinical diagnosis of sporadic PD (<i>n</i> = 13), and progressive supranuclear palsy patients (PSP, <i>n</i> = 9). We performed quantitative stereological analyses and optical metrology of fractalkine expression in neurons and endothelial cells, and immunoreactivities of microglial and CD4⁺ T cells within the substantia nigra of PD cases. These data were compared with findings seen in age-matched controls as well as MMD-LB and PSP.</p><p><strong>Results: </strong>In PD, MMD-LB, and PSP postmortem brains, fractalkine expression in remaining nigral neurons was significantly reduced but markedly increased in blood vessel endothelial cells. The density of microglia and CD4⁺ T cells in the substantia nigra was significantly higher in these disorders when compared to controls. The decline in neuronal fractalkine expression was inversely correlated with increases in microglial numbers in the substantia nigra, while higher levels of fractalkine in endothelial cells were positively correlated with CD4⁺ cells infiltrating the injured substantia nigra across groups. Both PD and PSP groups displayed a similar pattern of neuroinflammatory changes.</p><p><strong>Discussion: </strong>The downregulation of neuronal fractalkine expression caused by protein inclusions, such as abnormal alpha-synuclein or tau, is linked to microglia activation. When activated, microglia release cytokines that further stimulate endothelial cells to express fractalkine. This process recruits peripheral T cells, which infiltrate the injured brain. These findings indicate that the varying levels of neuronal and endothelial fractalkine expression in the substantia nigra contribute to neuroinflammatory activity in both synucleinopathy and tauopathy.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1557645"},"PeriodicalIF":4.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948700","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}