Neurochemistry international最新文献

{"title":"LC-MS/MS techniques for the analysis of steroid panel in human cerebrospinal fluid","authors":"Tereza Skodova ,&nbsp;Jana Vitku ,&nbsp;Ondrej Bradac ,&nbsp;Petr Skalicky ,&nbsp;Adela Bubenikova ,&nbsp;Radmila Kanceva ,&nbsp;Lucie Kolatorova","doi":"10.1016/j.neuint.2025.106080","DOIUrl":"10.1016/j.neuint.2025.106080","url":null,"abstract":"<div><div>The metabolic processes within the brain are reflected in the cerebrospinal fluid (CSF). It is in close contact with the nervous system, which is both target and source of multiple steroids. The aim of our study was to develop and validate robust, sensitive LC-MS/MS methods with and without derivatization step for the analysis of unconjugated steroids from all major steroid classes in CSF. The validation of the method without derivatization was performed for ten C19- steroids (dehydroepiandrosterone (DHEA), 7α-hydroxyDHEA, 7β-hydroxyDHEA, 7-ketoDHEA, testosterone, epitestosterone, dihydrotestosterone, 11-hydroxytestosterone, 11-ketotestosterone and androstenedione), ten C21- steroids (cortisol, 11-deoxycortisol, 21-deoxycortisol, cortisone, corticosterone, 11-deoxycorticosterone, pregnenolone, progesterone, 17-hydroxyprogesterone, aldosterone) and three C18- steroids (estrone, estradiol, estriol). The method with derivatization is validated for determination of eleven C19- steroids (testosterone, 11-ketodihydrotestosterone, 11-hydroxytestosterone, DHEA, 7α-hydroxyDHEA, 7β-hydroxyDHEA, 7-ketoDHEA, androstenedione, androsterone, epiandrosterone, 7β-hydroxyepiandrosterone) and six C21- steroids (cortisol, cortisone, corticosterone, pregnenolone, 17-hydroxypregnenolone, progesterone) in CSF. The method without derivatization is applicable for the determination of the majority of steroids in CSF, except for pregnenolone, 17-hydroxypregnenolone and DHEA, for which the derivatization method provides better sensitivity. When analyzing CSF samples of normal pressure hydrocephalus (NPH) patients, 11-ketodihydrotestosterone, epitestosterone, androsterone, epiandrosterone, 7β-hydroxyepiandrosterone, 7-ketoDHEA and 21-deoxycortisol were found to be below the LLOQ, suggesting that their presence is very limited. 17-hydroxypregnenolone, and 11-deoxycortisol were quantified for the first time, their CSF levels in NPH subjects are presented. We also observed significantly increased CSF levels of testosterone and 17-hydroxyprogesterone in men compared to women, both with NPH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106080"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370173","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":"Food restriction and amphetamine exposure synergistically enhance accumbal dopamine D1 receptor-mediated locomotor activity","authors":"Seohyeon Lee ,&nbsp;Hyung Shin Yoon ,&nbsp;Jeong-Hoon Kim","doi":"10.1016/j.neuint.2025.106081","DOIUrl":"10.1016/j.neuint.2025.106081","url":null,"abstract":"<div><div>Natural rewards such as food and drugs of abuse share the mesolimbic dopamine system, including the nucleus accumbens (NAcc), as a common neural pathway that influences appetite and addictive behavior. Ghrelin, an orexigenic hormone, acts synergistically with mesolimbic dopamine in this process. In the present study, we examined the effects of food restriction (FR) on plasma ghrelin levels and amphetamine (AMPH)-induced locomotor activity. Chronic FR (cFR) significantly enhanced AMPH-induced locomotor activity compared to normal feeding and acute FR (aFR), which was associated with increased plasma ghrelin and dopamine D1 receptor (D1R) expression levels in the NAcc. These effects were inhibited by either systemic or NAcc-specific administration of D1R or ghrelin receptor antagonists. Furthermore, rats under the aFR condition showed enhanced locomotor activity in response to intra-accumbal microinjection of the D1R agonist when pre-exposed to AMPH, whereas rats in the cFR condition showed these effects regardless of pre-exposures to either AMPH or saline. These results demonstrate that FR conditions interact with drugs of abuse via the accumbal ghrelin and D1R systems, thereby contributing to the expression of addictive behaviors. Notably, these findings suggest that dietary status should be considered during addiction treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106081"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399255","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":"Regional and cell type-specific activation of the unfolded protein response after kainate injection in mice","authors":"Ly Huong Nguyen ,&nbsp;Loc Dinh Nguyen ,&nbsp;Dat Xuan Dao ,&nbsp;Tsuyoshi Hattori ,&nbsp;Hiroshi Ishii ,&nbsp;Mika Takarada-Iemata ,&nbsp;Osamu Hori","doi":"10.1016/j.neuint.2025.106071","DOIUrl":"10.1016/j.neuint.2025.106071","url":null,"abstract":"<div><div>The unfolded protein response (UPR) is activated under different neuropathological conditions, such as brain ischemia, epilepsy, and neurodegeneration. We previously reported that a UPR transducer, activating transcription factor 6 (ATF6), and its downstream molecular chaperones in the endoplasmic reticulum (ER) have neuroprotective properties against excitotoxicity. In this study, we examined the temporal and spatial changes in the UPR activation after administration of an excitotoxic reagent, kainate (KA), into mice. RT-qPCR revealed enhanced expression of UPR genes, with peaks either on day 1 or day 3 after intrahippocampal KA injection. The status of the UPR was analyzed using ER stress-activated indicator (ERAI)-transgenic mice, in which the spliced form of XBP-1, downstream of the IRE1 branch of the UPR, can be monitored. ERAI-derived GFP signals were strongly observed in CA3 neurons and moderately observed in dentate gyrus neurons, but not in CA1 neurons, after KA injection. A small portion of the activated astrocytes was also positive for ERAI signals. Further studies revealed that ERAI signals were observed in both the soma and dendrites of neurons in regions with enhanced neuronal activity and resistance to KA toxicity. These results suggest that the UPR may be associated with the neuronal activity and survival after KA injection.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106071"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257016","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":"TREM2 deficiency aggravates neuroinflammatory response and cognitive impairment via disease-associated microglia in Parkinson's disease models","authors":"Zhang Piao ,&nbsp;Zhu Baoyu ,&nbsp;Feng Jiezhu ,&nbsp;Liang Xiaomei ,&nbsp;Huang Peiting ,&nbsp;He Chentao ,&nbsp;Deng Yiyu ,&nbsp;Lu Jiahong ,&nbsp;Wang Lijuan ,&nbsp;Zhang Yuhu","doi":"10.1016/j.neuint.2025.106068","DOIUrl":"10.1016/j.neuint.2025.106068","url":null,"abstract":"<div><div>This study explores whether Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) regulates the distinct disease-related microglia (DAM) phenotype and exerts a protective role in cognitive impairment in Parkinson's disease (PD). Adeno-associated virus carrying TREM2 shRNA (AAV-TREM2-shRNA) was injected into the bilateral hippocampus of the A53T α-Synuclein (α-Syn) transgenic PD mouse model; Additionally, lentivirus was transduced into BV2 microglial cells to knock out the expression of TREM2, which were subsequently stimulated with α-Syn preformed fibrils (PFF). Furthermore, cognitive status of mice, α-Syn aggregation, microglia status, expression of inflammatory factors, pro-inflammatory and anti-inflammatory DAM markers, MAPK and NF- κB pathway activation status and neuron apoptosis were evaluated. TREM2 deficiency induced cognitive impairment in A53T α-Syn PD mice by decreased performance in the novel objective recognition and Morris water maze tests. TREM2 knockdown resulted in synaptic loss, microglial activation, increased inflammatory factors, and MAPK and NF- κB pathway activation in the hippocampus of mice. In vitro, TREM2 deficiency exacerbated the inflammatory response of BV2 cells stimulated by α-Syn PFF by inhibiting anti-inflammatory DAM, and promoting neuronal apoptosis and Ser129-phosphorylation of α-Syn. TREM2 knockdown also promoted pro-inflammatory DAM activation and increased inflammatory factors expression via the ERK1/2 signaling pathway. Our findings suggest that TREM2 plays a protective role in cognitive impairment and promotes anti-inflammatory DAM activation via the ERK1/2 signaling pathway in PD mice, providing novel insight into the immunopathogenesis of cognitive impairments in PD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106068"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231095","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 epigenetic mechanism of sleep disorders related cognitive impairment","authors":"Meimei Guo ,&nbsp;Yuhan Liu ,&nbsp;Jiabin Zhou ,&nbsp;Yu Lei","doi":"10.1016/j.neuint.2025.106079","DOIUrl":"10.1016/j.neuint.2025.106079","url":null,"abstract":"<div><div>Sleep deprivation is a prevalent social problem affecting millions worldwide and can induce epigenetic alterations in the brain, impacting neuronal synaptic plasticity and cognitive function. The epigenetic alteration in clock genes significantly contribute to impaired learning and memory, though the precise mechanisms remain elusive. This review examines the prevalence of sleep loss and its impact on the cognitive function and circadian clock genes. We then discuss the intricate relationship between circadian clock genes and epigenetic alterations, and how these epigenetic changes may serve as potential targets for treating sleep disorders and memory impairment. Moving forward, further exploration of the cognitive impairment caused by sleep deprivation via epigenetic mechanism is essential to deepen our understanding of this complex interplay.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106079"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425146","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":"Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer's disease","authors":"Kanako Fujii ,&nbsp;Toshihide Takeuchi ,&nbsp;Yuzo Fujino ,&nbsp;Noriko Tanaka ,&nbsp;Nao Fujino ,&nbsp;Akiko Takeda ,&nbsp;Eiko N. Minakawa ,&nbsp;Yoshitaka Nagai","doi":"10.1016/j.neuint.2025.106082","DOIUrl":"10.1016/j.neuint.2025.106082","url":null,"abstract":"<div><div>Although amyloid β (Aβ)-targeting antibody therapies for Alzheimer's disease (AD) have recently been developed, their clinical efficacy remains limited, and issues such as high cost and adverse effects have been raised. Therefore, there is an urgent need for the establishment of safe and cost-effective therapeutic approaches that inhibit Aβ aggregation or prevent its accumulation in the brain. In this study, we report that arginine, a clinically approved and safe chemical chaperone, suppresses Aβ aggregation both <em>in vitro</em> and <em>in vivo</em>. We demonstrated using an <em>in vitro</em> assay that arginine inhibits the aggregation formation of the Aβ42 peptide in a concentration-dependent manner. In a <em>Drosophila</em> model of AD expressing the Aβ42 peptide with an Arctic mutation E22G, the oral administration of arginine dose-dependently reduced Aβ42 accumulation and rescued Aβ42-mediated toxicity. In an <em>App</em>^{<em>NL-G-F</em>} knockin mouse model harboring human APP familial mutations, the oral administration of arginine suppressed Aβ plaque deposition and reduced the level of insoluble Aβ42 in the brain. The arginine-treated <em>App</em>^{<em>NL-G-F</em>} knockin mice also showed the improvement of behavioral abnormalities and the reduced expression of the neuroinflammation-associated cytokine genes. These results indicate that the oral administration of arginine not only reduced Aβ deposition, but also ameliorated Aβ-mediated neurological phenotypes in animal models of AD. These findings identify arginine as a safe and cost-effective drug candidate that suppresses Aβ aggregation, and highlight its repositioning potential for rapid clinical translation for AD treatment. Arginine is also potentially applicable to a wide range of neurodegenerative diseases caused by protein misfolding and aggregation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106082"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145425090","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":"Transcription factor EB inhibition in response to genotoxic stress promotes apoptosis of glioblastoma cells","authors":"Seung-Ho Park ,&nbsp;Minseok Jeong ,&nbsp;Min-Jeong Kong,&nbsp;Kyung-Chul Choi","doi":"10.1016/j.neuint.2025.106087","DOIUrl":"10.1016/j.neuint.2025.106087","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM), one of the most malignant brain cancers, responds poorly to chemotherapy and surgery. Transcription factor EB (TFEB) is markedly overexpressed in GBM cells. We investigated whether TFEB contributes to resistance to genotoxic stress and whether its inhibition promotes apoptosis of GBM cells and glioma stem cells (GSCs). Specifically, we examined whether combined treatment with etoposide and SAHA overcomes TFEB-mediated resistance and enhances apoptotic cell death. We examined the effects of etoposide, a topoisomerase II inhibitor, and SAHA, a histone deacetylase inhibitor, on TFEB expression and apoptotic signaling in human GBM cells and GSCs. To assess TFEB-mediated drug resistance, we measured cell viability, proliferation, and tumorsphere formation following single or combined treatments. Apoptotic signaling was analyzed by western blotting, MTT assays, and tumorsphere formation assays. Functional roles of TFEB were further investigated using overexpression and shRNA knockdown approaches. Treatment with etoposide induced apoptosis and reduced TFEB expression in GBM cells. Co-treatment with etoposide and SAHA synergistically increased cleaved PARP and phosphorylated H2AX levels, indicating enhanced apoptotic activity. In TFEB-overexpressing and knockdown GBM cells, apoptosis sensitivity varied according to TFEB expression levels. In GSCs, combination treatment significantly suppressed cell proliferation and tumorsphere formation, accompanied by reduced TFEB expression and oligomerization, and increased apoptosis. Our findings suggest that TFEB promotes the chemoresistance of GBM tumors and GSCs by suppressing apoptosis. Co-treatment with etoposide and SAHA inhibits TFEB activity and enhances apoptotic cell death, representing a promising therapeutic strategy for treating malignant brain tumors.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106087"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538119","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":"Psychotropic and neurodegenerative drugs modulate platelet activity via the PAF pathway","authors":"Savvato Kosidou ,&nbsp;Zisis Zannas ,&nbsp;Anna Ofrydopoulou ,&nbsp;Dimitra A. Lambropoulou ,&nbsp;Alexandros Tsoupras","doi":"10.1016/j.neuint.2025.106073","DOIUrl":"10.1016/j.neuint.2025.106073","url":null,"abstract":"<div><div>Mild psychiatric conditions such as anxiety and depression, as well as severe disorders like schizophrenia and neurodegenerative diseases, are increasingly recognized as systemic inflammatory conditions. Platelets possess both hemostatic and immunomodulatory roles in these situations, with sharing key molecular pathways with the central nervous system, offering thus a valuable peripheral model for evaluating psychotropic drug effects. Platelet-activating factor (PAF), a potent thrombo-inflammatory mediator, has emerged as a potential link between the two systems, yet its involvement in drug responses remains understudied. This study systematically investigates the effects of psychotropic drugs (i.e. antidepressants, antipsychotics and anxiolytics), and neuroprotective (anti-Alzheimer's/Anti-Parkinson's) drugs on platelet aggregation, focusing on PAF-pathway in comparison to a control platelet agonist, ADP. Using ex vivo light transmission aggregometry, we determined IC₅₀ values for each drug and analyzed the impact of selected drug combinations, in which the NSAID diclofenac was also included. Results revealed that most of the compounds assessed inhibited more effectively the PAF-induced aggregation of platelets compared to their effect on the ADP-pathway, with perphenazine showing the greatest anti-PAF potency. Several drug combinations, notably those including alprazolam and diclofenac, demonstrated significant synergistic effects. These findings suggest that commonly prescribed psychotropic drugs and medications for neurodegenerative disorders can influence platelet activity, mostly through the PAF-pathway, and that their interactions with NSAIDs may amplify their efficacy. Nevertheless, some drugs and their combinations induced lysis of platelets at much higher concentrations than their IC50 values, which stems safety concerns for their use.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106073"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297908","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":"Histone lactylation is associated with METTL3-dependent LCN2 m6A modification and astrocyte activation after intracerebral hemorrhage","authors":"Ling Gao ,&nbsp;Xiaobin Zheng ,&nbsp;Cong Tan ,&nbsp;Li Peng ,&nbsp;Chuang Wang ,&nbsp;Zhongtao Zheng ,&nbsp;Jiangli Han ,&nbsp;Jian Wang ,&nbsp;Zhao Yang ,&nbsp;Weiming Chen","doi":"10.1016/j.neuint.2025.106069","DOIUrl":"10.1016/j.neuint.2025.106069","url":null,"abstract":"<div><h3>Background</h3><div>Intracerebral hemorrhage (ICH) is a major cause of secondary brain injury (SBI), which results in severe neurological deficits and poor clinical outcomes. Elevated serum lactate levels have been associated with unfavorable outcome in ICH patients. However, the role of lactate in ICH-induced SBI remain poorly understood.</div></div><div><h3>Method</h3><div>An autologous blood injection mouse model of ICH and lactate-treated C8D1A cells were employed as the <em>in vivo</em> and <em>in vitro</em> models, respectively. The establishment of ICH model was validated by behavior tests, and brain injury was assessed by H&amp;E and Nissel staining. qRT-PCR, Western blot and IHC analysis were used to detect the expression of key molecules. Immunofluorescent (IF) staining was employed to evaluate astrocyte activation. Pro-inflammatory cytokine release was monitored by ELISA assay. The interaction between H3K18la and METTL3 was assessed by ChIP assay, and the association between METTL3 and LCN2 mRNA was assessed by RNA immunoprecipitation (RIP) assay.</div></div><div><h3>Results</h3><div>The levels of lactate, METTL3 and LCN2 are elevated in ICH model in mice. The inhibition of lactate decreased METTL3 expression and alleviated ICH-induced SBI. Mechanistically, histone H3K18 lactylation was associated with the upregulated levels of METTL3 and m⁶A in mouse brains. METTL3 regulated the m⁶A modification of LCN2 and upregulated its expression. In ICH mice, silencing of LCN2 inhibited A1 astrocyte activation. Histone lactylation-modulated LCN2 m⁶A modification is involved in astrocyte activation and the regulation of SBI in ICH mice.</div></div><div><h3>Conclusion</h3><div>These results suggested a mechanism whereby histone lactylation is implicated in the activation of A1 astrocytes through METTL3-mediated LCN2 m⁶A modification.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106069"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249159","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":"Neuronal FSTL4 negatively regulates BDNF-mediated neuron-glioma interaction","authors":"Yan Sun ,&nbsp;Mi Xiao ,&nbsp;Xunhui Wang ,&nbsp;Yanchun Xu ,&nbsp;Anbin Chen ,&nbsp;Bin Li ,&nbsp;Baohui Feng ,&nbsp;Bangbao Tao","doi":"10.1016/j.neuint.2025.106072","DOIUrl":"10.1016/j.neuint.2025.106072","url":null,"abstract":"<div><div>Gliomas exploit various molecular pathways to promote their survival, proliferation, and invasion. Recent studies reveal the complex neuron-glioma interaction and BDNF plays a major role in this interaction. However, it's unclear whether and how the BDNF-mediated cross-talk between neurons and gliomas is regulated. FSTL4 is reported to negatively regulate BDNF maturation. Here, we hypothesized that neuronal FSTL4 may negatively regulate BDNF-mediated neuron-glioma cross-talk. By using a combination of approaches like chemogenetic activation of primary neurons and CRISPR knockout/activation of endogenous FSTL4, we show that activated primary neurons support the proliferation of co-cultured glioma cells and neuronal BDNF secretion mediates this neuron-glioma interaction via activating TrkB in glioma cells. In addition, this process is negatively regulated by neuronal FSTL4 as its CRISPR KO in primary neurons further supports the proliferation of co-cultured glioma cells. Importantly, CRISPR activation of endogenous FSTL4 expression in primary neurons results in impaired ability to support co-cultured glioma cells, highlighting the therapeutic potential of activating endogenous FSTL4 for glioma treatment. Taken together, our study shows that the FSTL4/BDNF/TrkB axis plays an essential role in fine-tuning the neuron-glioma interaction and targeting this interplay with CRISPR tools may help to develop novel therapeutic strategies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"191 ","pages":"Article 106072"},"PeriodicalIF":4.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285368","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}