Neurochemical Research最新文献

{"title":"Mito-TEMPO Mitigates Fibromyalgia Induced by Reserpine in Rats: Orchestration Between SIRT1, Mitochondrial Dynamics, Endoplasmic Reticulum and miRNA-320.","authors":"Heba S Zaky, Nermin T El-Said, Amany S Aboutaleb, Albatoul Allam, Mona Mansour, Hebatalla I Ahmed, Somaia A Abdel-Sattar","doi":"10.1007/s11064-025-04424-9","DOIUrl":"https://doi.org/10.1007/s11064-025-04424-9","url":null,"abstract":"<p><p>Fibromyalgia (FM) is a chronic disorder that lacks both well-defined underlying causes and effective treatments. Mito-TEMPO (MIT) is a mitochondrial-specific antioxidant that has demonstrated benefits in many cancerous, renal, cardiovascular, and neurodegenerative disorders. However, the therapeutic effect of MIT on FM remains ambiguous. The objective of the current work is to illuminate the use of MIT for FM and its prospective mechanisms. Here, we used the FM rat model induced by three days of subcutaneous reserpine injection (1 mg/kg) and examined the role of MIT on SIRT1 activation and other implicated molecular pathways. Behavioral tests showed that MIT (0.7 mg/kg) can effectively alleviate the locomotor, nociceptive, and depressive-like behaviors in reserpinized rats, an effect that simultaneously reconciles the balance of monoamines in the rat brain. Western blot analysis showed that MIT up-regulates SIRT1 and improves the expression of mitochondrial dynamics proteins (DRP1 and OPA1) and the endoplasmic reticulum protein (CHOP). Furthermore, MIT treatment significantly enhanced the SOD and CAT activities and decreased the brain contents of NF-κB, TNF-α, and BAX, but significantly enriching the Bcl-2 content. Lastly, MIT treatment significantly reduced the genetic expression of miRNA-320 following RES treatment. All the measured parameters showed a significant correlation with SIRT1 expression. Our results suggest that MIT provides antioxidant, anti-apoptotic, and anti-inflammatory impacts on the FM rat model, with proposed mechanisms involved activating the SIRT1 pathway to regulate mitochondrial dynamics, endoplasmic reticulum stress, as well as miRNA-320. Thus, MIT has the potential to be an effectual drug candidate for FM treatment.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":"172"},"PeriodicalIF":3.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of NLRP3 Inflammasome Alleviates Postoperative Cognitive Impairment by Suppressing the HMGB-1/TLR4/NF-κB Pathway.","authors":"Gang Ma, Xin Jiang, Xiangkun Meng, Zhendong Liu, Xue Ma, Hao Wang","doi":"10.1007/s11064-025-04416-9","DOIUrl":"https://doi.org/10.1007/s11064-025-04416-9","url":null,"abstract":"<p><p>Perioperative neurocognitive disorders (PNDs), main complications of surgery and anesthesia in the elderly, are mainly associated with neuroinflammation and remain poorly understood. This study aimed to explore the function of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in the development of PNDs. Male C57BL/6 mice underwent right carotid artery exposure surgery, with or without treatment with adeno-associated virus vectors carrying NLRP3 (AAV-NLRP3), which was administered either intracerebroventricularly or via tail vein injection. Mouse brain tissue was collected 24 h postoperatively for biochemical assays. Another group of mice was subjected to the Morris water maze and novel object recognition tests to assess their learning and memory abilities. The results revealed that surgery and anesthesia increased NLRP3 protein expression level and programmed cell death in the hippocampus of mice, leading to impaired learning and memory, while AAV-NLRP3 treatment attenuated these effects. Additionally, inhibition of high-mobility group protein box 1 (HMGB-1) expression level alleviated surgery-induced upregulation of Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLRP3 in the hippocampus of mice. The NLRP3 inflammasome emerged critical for the occurrence of neuroinflammation and postoperative cognitive impairment, which could be alleviated by inhibiting NLRP3 inflammasome via the HMGB-1/TLR4/NF-κB pathway.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":"173"},"PeriodicalIF":3.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Mechanism of Dihydromyricetin in Alleviating Depressive-Like Behavior in Rats Based on Network Pharmacology","authors":"Xue Li,&nbsp;Miaoqi Chen,&nbsp;Decheng Wei,&nbsp;Pengsheng Wei,&nbsp;Yanzong Jiang,&nbsp;Jiaqi Chen,&nbsp;Xiaomeng duan,&nbsp;Zitong Wang,&nbsp;Yuchuan Zhang,&nbsp;Dafeng Bai,&nbsp;Hui Jia,&nbsp;Ge Jin","doi":"10.1007/s11064-025-04419-6","DOIUrl":"10.1007/s11064-025-04419-6","url":null,"abstract":"<div><p>Depression is a chronic and recurrent neuropsychiatric disorder with complex pathophysiology. Dihydromyricetin (DMY), a bioactive flavonoid compound isolated from Ampelopsis grossedentata (commonly known as rattan tea), has demonstrated multiple pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antimicrobial activities. In the present study, a well-established rodent model of depression was generated through chronic unpredictable mild stress (CUMS) paradigm combined with social isolation. Following eight weeks of DMY intervention, comprehensive behavioral assessments were conducted to validate both the successful establishment of the depression model and the therapeutic efficacy of DMY treatment. We employed network pharmacology approaches to systematically predict potential antidepressant targets of DMY. Further mechanistic investigations were performed to elucidate the underlying molecular pathways, providing novel perspectives for developing innovative antidepressant therapeutics.Integrating network pharmacology prediction with molecular biology validation, our findings revealed that DMY exerts significant antidepressant-like effects through suppression of the advanced glycosylation end products (AGEs)-RAGE signaling pathway, activation of the nuclear factor E2-related factor 2 (NRF2)-mediated antioxidant defense system, and upregulation of synaptic plasticity-related proteins including postsynaptic density protein 95 (PSD95) and synaptophysin (SYP). These results suggest that DMY may represent a promising natural therapeutic candidate for depression treatment.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ubiquitination and Degradation of SH2B3 Mediated by MEF2A/WWP2 Axis Restores Microglial Homeostasis to Alleviate Cerebral Microvascular Endothelial Cell Injury in Ischemic Stroke","authors":"Si-xian Lin,&nbsp;Chenglong Shi,&nbsp;Lei Zhao,&nbsp;Lei Xian,&nbsp;Wenwu Yang,&nbsp;Zhenyu Wang,&nbsp;Longjie Qin,&nbsp;Xiao-li Min,&nbsp;Jiasheng Yu","doi":"10.1007/s11064-025-04406-x","DOIUrl":"10.1007/s11064-025-04406-x","url":null,"abstract":"<div><p>Ischemic stroke (IS) is a severe disease. The altered activation states of microglia play important roles in IS. In present study, a total of 125 C57BL/6 mice was used (<i>N</i> = 6 per group). Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) were performed for in vivo and in vitro model construction. The infarct size was detected using TTC staining. The nerve injury was evaluated by a neurological deficit score. OGD-treated brain microvascular endothelial cells (BMECs) were co-cultured with BV2 cells. Cell viability was determined by CCK-8 assay, and the apoptosis rate was identified by flow cytometry analysis. Transendothelial electronic resistance (TEER) of the cells was measured by TEER measurement. Molecular interactions were analyzed using dual-luciferase reporter gene, ChIP, and Co-IP assays. All in vitro experiments were conducted with three replicates, and each experiment was performed in triplicate. We found that Src Homology 2B Adaptor Protein 3 (SH2B3) was overexpressed in the cerebral cortex tissues of MCAO treated mice (<i>P</i> &lt; 0.01), and BMECs co-cultured with BV-2 cells under OGD conditions (<i>P</i> &lt; 0.01). SH2B3 knockdown or Myocyte Enhancer Factor 2 A (MEF2A) overexpression reduced infarct size and improved neurological function in MCAO mice. SH2B3 knockdown enhanced OGD-treated cell viability (<i>P</i> &lt; 0.05), inhibited cell apoptosis (<i>P</i> &lt; 0.05) in BMECs, and ameliorated BBB (<i>P</i> &lt; 0.01). Moreover, SH2B3 knockdown changed the activation status of microglia. MEF2A promoted the transcriptional activation of WW Domain Containing E3 Ubiquitin Protein Ligase 2 (WWP2) and WWP2 promoted the ubiquitination and degradation of SH2B3. SH2B3 overexpression reversed the effects of MEF2A overexpression on microglia states, BMECs injury and BBB function. In summary, MEF2A promoted the ubiquitination-mediated degradation of SH2B3 via transcription up-regulating WWP2, then changed the activation status of microglia, thus ameliorating BMEC injury, and finally ameliorating IS injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroplasticity After Hypoxic-Ischemic Brain Injury in Neonatal Pigs Based on Time-Dependent Behavior of 1H-MRS-Tau Protein and Synaptic Associated Proteins and Synaptic Structure Analysis","authors":"Sijia Zhao,&nbsp;Yang Zheng","doi":"10.1007/s11064-025-04421-y","DOIUrl":"10.1007/s11064-025-04421-y","url":null,"abstract":"<div><p>This study investigated the effects of hypoxic-ischemic (HI) injury on neonatal neuroplasticity using the following approaches: Magnetic Resonance Spectroscopy (¹H-MRS) imaging to analyze dynamic changes in tau protein levels, immunofluorescence staining to evaluate synaptophysin (SYP), neurocan (Neu), and tau protein, and utilizing transmission electron microscopy (TEM) to examine synaptic ultrastructure at multiple time points. A total of 59 healthy neonatal pigs were included, with 10 in the control group and 43 in the HI model group. The results demonstrated that SYP immunostaining intensity peaked at 6–12 h after HI before declining. Neu expression exhibited an initial decrease, followed by a transient increase and subsequent reduction, reaching its lowest level at 6–12 h after HI. Tau protein levels increased initially after HI, peaked at 24–48 h after HI, and subsequently decreased. SYP was negatively correlated with Neu with a correlation coefficient of -0.877. SYP was not correlated with Tau, neither was Neu with Tau. Compared with the control group, the number of synaptic vesicles decreased, and Post-Synaptic Density (PSD) thickness increased 6–12 h after HI. At 12–24 h after HI, the number of synaptic vesicles increased, and PSD thickness slightly decreased. At 24–48 h after HI, the vesicle number decreased, PSD became thinner, interrupting continuity, mitochondria swelled, and mitochondrial cristae blurred and disappeared. The findings suggest that the expression of Tau, SYP, and Neu is linked to alterations in synaptic and myelin structures, reflecting varying aspects of neural plasticity following HI injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04421-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117747","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":"Plumbagin Alleviates Social Behavior Deficits in a Valproic Acid Model of Autism by Reducing Glial Activation and Oxidative Stress in the Cerebellum","authors":"Nasrin Nosratiyan,&nbsp;Olia Hamzeh,&nbsp;Maryam Ghasemi-Kasman","doi":"10.1007/s11064-025-04425-8","DOIUrl":"10.1007/s11064-025-04425-8","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects multiple brain regions, including the cerebellum. It is characterized by behavioral alterations that significantly impact various aspects of patients’ lives. The present study was conducted to examine the anti-inflammatory, antioxidant, and neuromodulatory activities of plumbagin (PLB) in a valproic acid (VPA)-induced autism model. Pregnant rats received an intraperitoneal (i.p.) injection of VPA (600 mg/kg) on day 12.5 of pregnancy. After birth, offspring were orally administered different doses of PLB (0.25, 0.5, and 1 mg/kg) from days 7 to 35. Social interaction and preference were assessed via a three-chamber social assay. Hematoxylin‒eosin (H&amp;E) staining was performed to observe histopathological changes in the cerebellum. Moreover, astrocyte and microglial activation were evaluated by immunostaining. The gene expression levels of <i>Nrf2</i>, <i>HO-1</i>, <i>BDNF</i>, <i>SIRT1</i>, <i>IL-6</i>, <i>IL-1β</i>, <i>TNF-α</i>, and <i>TGF-β1</i> were evaluated via quantitative real-time PCR (qRT‒PCR). These findings revealed that PLB treatment significantly alleviates social impairments. PLB ameliorated the loss of Purkinje cells and the number of activated astrocytes and microglia in the cerebellum. PLB administration also upregulated the gene expression of <i>Nrf2</i>, <i>HO-1</i>, <i>BDNF</i>, <i>SIRT1</i>, and <i>TGF-β1</i> and downregulated the <i>IL-6</i> expression level. Overall, it seems that PLB diminishes autism-related damage in the cerebellum through neuromodulatory activities and attenuation of oxidative stress and inflammation. </p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA Promotes Functional Recovery After Spinal Cord Injury by Inhibiting Neuron and Oligodendrocyte Ferroptosis Through the GPX4/ACSL4 Axis","authors":"Luchun Xu,&nbsp;Guozheng Jiang,&nbsp;Shuyin Tan,&nbsp;Yukun Ma,&nbsp;Jiawei Song,&nbsp;Yushan Gao,&nbsp;Guanlong Wang,&nbsp;Jiaojiao Fan,&nbsp;Yongdong Yang,&nbsp;Xing Yu","doi":"10.1007/s11064-025-04414-x","DOIUrl":"10.1007/s11064-025-04414-x","url":null,"abstract":"<div><p>Spinal cord injury (SCI) induces severe functional impairments and involves intricate secondary injury mechanisms. Tanshinone IIA (TIIA), a key bioactive component of <i>Salvia miltiorrhiza</i>, exhibits neuroprotective potential, yet its role in ferroptosis regulation post-SCI remains undefined. This study explored the protective effects and underlying mechanisms of TIIA in SCI. In a rat SCI model, TIIA markedly enhanced hind limb motor function and preserved histopathological integrity while mitigating mitochondrial damage, ferroptosis, and oxidative stress. TIIA attenuated ferroptosis by reducing reactive oxygen species (ROS), malondialdehyde (MDA), and acyl-CoA synthetase long-chain family member 4 (ACSL4) while elevating glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase 4 (GPX4) levels. Mechanistically, TIIA suppressed ferroptosis through modulation of the GPX4/ACSL4 axis. The ferroptosis inducer RSL3 abrogated these protective effects, further validating this mechanism. These findings highlight the therapeutic potential of TIIA in SCI by targeting the GPX4/ACSL4 pathway to attenuate ferroptosis and promote functional recovery.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases","authors":"Kai Gao,&nbsp;Albert Cheung-Hoi Yu","doi":"10.1007/s11064-025-04418-7","DOIUrl":"10.1007/s11064-025-04418-7","url":null,"abstract":"<div><p>Astrocytes support neurons by maintaining health, regulating the environment, and aiding synaptic transmission, while glutamate is vital for excitatory signaling in learning and memory. The “glutamate-glutamine cycle,” verified by Hertz and Schousboe, illustrates the interaction between neurons and astrocytes in glutamate regulation. Recent studies show astrocytes not only manage glutamate levels but also influence synaptic activity through gliotransmission and contribute to brain energy via glutamate metabolism. Dysregulation of this signaling is linked to neurological disorders like epilepsy and Alzheimer’s. This mini-review will explore research progress on astrocytes and glutamate, highlighting glutamate’s role in brain function and disease.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling Epilepsy Associated Alzheimer’s Disease Through Mitochondrial Complex-I Inhibition: Neurochemical and Therapeutic Perspectives","authors":"Arvinder Kaur,&nbsp;Rajesh Kumar Goel","doi":"10.1007/s11064-025-04413-y","DOIUrl":"10.1007/s11064-025-04413-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is comorbid condition in epilepsy. Mitochondrial dysfunction serves as a common disease mechanism. This study aimed to develop a new mouse of epilepsy-associated AD by inhibiting mitochondrial complex-I and exploring neurochemistry to identify therapeutic targets. Swiss albino mice were divided into naïve, corneal kindled (CK), and rotenone corneal kindled (RCK) groups. CK underwent epileptogenesis by using 6 Hz corneal kindling model (15 mA, 20 V, 6-Hz, 3 s for 15 days), while RCK underwent both epileptogenesis and mitochondrial dysfunction via rotenone administration (2.5 mg/kg, i.p daily). RCK mice exhibited generalised tonic-clonic seizures, cognitive deficits, oxidative stress, and Aβ/tau deposition. Neurochemical analysis showed increased glutamate, kynurenine, and reduced GABA, taurine, monoamines, antioxidants, and acetylcholinesterase activity. The RCK model replicates construct and face validity of both epilepsy and AD, may serve as a new model to investigate shared disease mechanisms and associated altered neurotransmitter as therapeutic approach.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Ecto-5’-Nucleotidase/CD73 Expression and Malignancy Parameters in Early- and Late- Passage C6 Glioma Cells","authors":"Fabiana M. Manica,&nbsp;Luis Felipe I. Campesato,&nbsp;Juliete Nathali Scholl,&nbsp;Elizandra Braganhol,&nbsp;Leticia S. Bergamin,&nbsp;Maria Isabel A. Edelweiss,&nbsp;Guido Lenz,&nbsp;Jean Sevigny,&nbsp;Fabrício Figueiró,&nbsp;Ana Maria O. Battastini","doi":"10.1007/s11064-025-04409-8","DOIUrl":"10.1007/s11064-025-04409-8","url":null,"abstract":"<div><p>Glioblastoma (GB) is a highly aggressive tumor characterized by its proliferative and invasive behavior. Ecto-5’-nucleotidase (e5NT/CD73), an enzyme that hydrolyzes extracellular AMP to adenosine, plays a pivotal role in cellular processes and has been involved in tumor progression, with its upregulation observed in several cancers. C6 glioma cells, widely used in GB research, exhibit changes in morphology and biochemical properties, depending on their passage number. This study investigates malignancy-related parameters in early-passage (EPC6) and late-passage (LPC6) C6 cells, highlighting the e5NT/CD73 expression and activity. The results presented here demonstrate that the LPC6 cells showed reduced CD73 expression and lower e5NT/CD73 AMPase activity compared to the EPC6 cells. Despite a higher proliferation rate in the LPC6 cells after two days of growth, Ki67 expression analysis revealed comparable proliferation between the two cell types at 5 and 10 days. Notably, the EPC6 cells showed enhanced proliferation in response to exogenous AMP, whereas the LPC6 cells did not. Furthermore, the EPC6 cells exhibited decreased adhesion but greater colony formation than the LPC6 cells. The LPC6 cells showed a significant reduction in migration, likely due to the loss of e5NT/CD73 migratory function. In the in vivo results, all the rats injected with EPC6 cells developed tumors displaying all the histopathological features of GB, whereas the LPC6 cells formed smaller tumors. Confirming the role performed by e5NT/CD73 in glioma progression, protein silencing significantly reduced tumor growth in vivo. These findings underscore the critical role of purinergic signalling in GB progression and emphasize the need for careful monitoring of passage number and e5NT/CD73 in in vitro experiments.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}