Brain Research Bulletin最新文献

{"title":"Therapeutic time window of sodium of Danshensu on cerebral ischemia and its mechanism of inhibiting oxidative stress and ferroptosis through Nrf2 pathway","authors":"Chao Guo ,&nbsp;Zhongying Ma ,&nbsp;Xingru Tao ,&nbsp;Kai Gao,&nbsp;Wei Zhang,&nbsp;Aidong Wen,&nbsp;Yi Ding,&nbsp;Jingwen Wang","doi":"10.1016/j.brainresbull.2025.111396","DOIUrl":"10.1016/j.brainresbull.2025.111396","url":null,"abstract":"<div><h3>Background</h3><div>Sodium of Danshensu (SDSS), extract of <em>salvia miltiorrhiza root</em>, has been shown to have neuroprotective effects on ischemic stroke (IS) in our previous studies. However, its therapeutic time window and mechanism of action remain unclear. Ferroptosis exerts a crucial feature in the development and progression of IS. Nuclear factor-E2-related factor 2 (Nrf2) can positively regulate the transcription of Recombinant Solute Carrier Family 7, member 11 (SLC7A11) and glutathione peroxidase (GPX4) genes that combat lipid peroxidation in ferroptosis.</div></div><div><h3>Purpose</h3><div>The current study aimed to assess therapeutic time window of SDSS and the pharmacological mechanism involved in Nrf2-mediated oxidative stress and ferroptosis.</div></div><div><h3>Methods</h3><div>Mice with transient middle cerebral artery occlusion (MCAO) and HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) were induced to simulate IS. Mice were administered SDSS at 1, 3, 6 or 9 h after MCAO to determine the therapeutic time window of SDSS. MicroRNA-seq was conducted to analyze differentially expressed genes in both the MCAO and the SDSS treatment group. The interaction between SDSS and Nrf2 was also investigated using molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR) experiments. Furthermore, the neuroprotection of SDSS was investigated in Nrf2-deficient mice to assess the activation mechanism of the Nrf2/GPX4 axis by SDSS. The biomarkers (Fe^2 + content, ROS, MDA, GSH, GSH/GSSG), mitochondrial structure, these proteins (Nrf2, SLC7A11, GPX4, FTH1, HO-1, ACSL4 and TFRC) expression were detected by commercial kits, transmission electron microscope (TEM) and Western blotting, respectively.</div></div><div><h3>Results</h3><div>The therapeutic time window of SDSS should be within 6 hours after MCAO, beyond which SDSS cannot play a therapeutic role. SDSS played a neuroprotective affection in mice and HT22 cells by restraining ROS, MDA and Fe²⁺ content, elevating GSH level and GSH/GSSG ratio. At the molecular mechanism, SDSS can bind to Nrf2, improve Nrf2 activity and nuclear expression, further enhance SLC7A11, GPX4, FTH1, HO-1 expression and reduce ACSL4 and TFRC expression. However, the neuroprotective effects of SDSS and its effect on ferroptosis-related proteins were partially reversed in Nrf2-deficient mice.</div></div><div><h3>Conclusion</h3><div>The therapeutic time window of SDSS for ischemic stroke is relatively wide. The administration of SDSS can potentially mitigate brain damage through the inhibition of oxidative damage and ferroptosis, which is partly regulated by the Nrf2/GPX4 axis. Therefore, SDSS is a promising candidate for the treatment of ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111396"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116115","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":"Characteristic of motor-related cortical network during stimulating at the affected or bilateral limbs of stroke patients by acupuncture","authors":"Ziwen Yuan ,&nbsp;Fei Mao ,&nbsp;Zimo Liu ,&nbsp;Shubo Xing ,&nbsp;Liu Yang ,&nbsp;Wenping Wu ,&nbsp;Weiwei Xu ,&nbsp;Jingyuan Deng ,&nbsp;Gang Wang","doi":"10.1016/j.brainresbull.2025.111393","DOIUrl":"10.1016/j.brainresbull.2025.111393","url":null,"abstract":"<div><h3>Background</h3><div>The compensatory pattern between the two hemispheres after stroke has been the focus of research. Some evidence suggests bilateral stimulation more effectively engages networks across both hemispheres compared to the affected side only.</div></div><div><h3>Objectives</h3><div>To explore whether the stimulating at bilateral limbs of stroke patients by acupuncture may better engage compensatory reorganization between the hemispheres compared to stimulating at the hemiplegic limb.</div></div><div><h3>Methods</h3><div>Conscious patients with hemiplegia were screened. Brain activity was assessed by the functional near-infrared spectroscopy(fNIRS) in three states: no treatment, acupuncture on the affected side, and then acupuncture on both sides. Brain activation and directed functional connectivity(FC) was analyzed between the two acupuncture strategies.</div></div><div><h3>Results</h3><div>Acupuncture of bilateral limbs resulted in stronger activation in the primary motor cortex(M1) of the ipsilesional hemisphere than acupuncture of the affected side only. And no significantly enhanced activation of the contralesional hemisphere was observed after acupuncture on the healthy limb. Besides, the FCs from the ipsilesional premotor cortex to the contralesional sensory-related area were significantly enhanced, and the FCs from the sensory area to motor area within the ipsilesional hemisphere were also significantly enhanced. Additionally, FCs from contralesional M1 to ipsilesional motor area were attenuated.</div></div><div><h3>Conclusion</h3><div>Stimulating at bilateral limbs by acupuncture could lead to greater brain network remodeling in the motor-related areas compared to stimulating solely at the affected side, and not through more stimulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111393"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105534","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":"Electroacupuncture alleviates the relapse of behaviors associated with pain sensory memory and pain-related aversive memory by activating MORs and inhibiting GABAergic neurons in the insular cortex","authors":"Mengdi Xie ,&nbsp;Yuxin Hu ,&nbsp;Miaoling Ji ,&nbsp;Zui Shen,&nbsp;Xiangnan Yao,&nbsp;Haiju Sun,&nbsp;Xixiao Zhu,&nbsp;Yiping Xie,&nbsp;Shuting Zhou,&nbsp;Chi Xu,&nbsp;Xiaofen He,&nbsp;Boyi Liu,&nbsp;Jianqiao Fang,&nbsp;Xiaomei Shao","doi":"10.1016/j.brainresbull.2025.111394","DOIUrl":"10.1016/j.brainresbull.2025.111394","url":null,"abstract":"<div><div>Pain memory, which includes sensory and emotional memory, is one of the main causes of pain complications and prolongation. Recent research has identified the insular cortex (IC) as a critical brain region involved in the integration of information pertaining to pain, emotion, reward, cognition and memory. GABAergic neuronal activity in the IC has been demonstrated to be strongly correlated with the manifestation of pain-related aversive behavior. Electroacupuncture (EA) relieves pain-related aversive memory by activating μ opioid receptors (MORs) in the IC. The results of this study demonstrate that activating MORs in the IC may inhibit GABAergic neuron activity and thus alleviate the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The relapse of such behaviors was found to be alleviated by EA in model mice; however, antagonism of MORs in the IC reversed the therapeutic effect of EA. In consideration of these findings, we suggest that EA may affect GABAergic neuron activity through activation of MORs in the IC thereby alleviating the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The study provides novel insights into the mechanisms by which EA chronic pain and behaviors associated with chronic pain-related aversive memory.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111394"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118795","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":"An experimental study on the optimal timing of modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats","authors":"Qianqian Wang ,&nbsp;Jiahui Hu ,&nbsp;Yueqin Tian ,&nbsp;Chao Li ,&nbsp;Nenggui Xu ,&nbsp;Hongmei Wen ,&nbsp;Zulin Dou ,&nbsp;Qiuping Ye","doi":"10.1016/j.brainresbull.2025.111390","DOIUrl":"10.1016/j.brainresbull.2025.111390","url":null,"abstract":"<div><div>As a novel neuroregulatory technique, modified pharyngeal electrical stimulation (mPES) has demonstrated clinical potential in improving swallowing function. However, there is a notable lack of animal studies exploring this approach. While our previous research validated the optimal parameters for post-stroke dysphagia (PSD) in rats, it did not establish the ideal timing for initiating treatment. This study aimed to identify the optimal time for mPES treatment in the rehabilitation of PSD. Seventy-four Sprague-Dawley (SD) rats were randomly assigned to six groups: a model group, a sham group, and four mPES groups (with treatment initiated at 24 h, 72 h, 5 days, and 7 days post-modeling). All treatment groups received mPES therapy for three consecutive days. Following the intervention, swallowing function was re-evaluated using videofluoroscopic swallowing studies (VFSS), and western blotting analysis was conducted to assess the excitability of sensorimotor cortex. Compared to the model group, all mPES groups exhibited improvements in swallowing function. Among them, the group receiving treatment 72 h post-modeling demonstrated the most significant enhancements (<em>P &lt; 0.05</em>). In addition, The expressions of N-methyl-D-aspartic acid receptor (NMDAR1) and Vesicular glutamate transporter 2 (Vglut2) were higher in the 72-hour group compared to the 7 day group (<em>P &lt; 0.05</em>). This study concluded that mPES treatment was effective when initiated at any of the tested time points-24 h, 72 h, 5 days, or 7 days post-modeling. However, initiating treatment 72-hour post-modeling yielded the greatest improvement in swallowing function in PSD rats.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111390"},"PeriodicalIF":3.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109703","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":"Potential risk factors of susceptibility to recurrent depression","authors":"Shuzhuo Wang ,&nbsp;Lei Guo ,&nbsp;Chuang Wang","doi":"10.1016/j.brainresbull.2025.111374","DOIUrl":"10.1016/j.brainresbull.2025.111374","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in the BicC family RNA binding protein 1 (BICC1). However, the potential risk factors that regulate BICC1 and affect susceptibility to recurrent depression remain unclear.</div></div><div><h3>Methods</h3><div>Herein, we firstly tested the heat shock protein 90 (HSP90), hypoxia-inducible factor 1-alpha (HIF1α), and BICC1 in the serum of the patients that were in first-episode or recurrent depression, as well as their controls. Then, through re-exposure to chronic unpredictable mild stress (CUMS) in mice, an animal model of recurrent depression was assessed. And the expression of HSP90, HIF1α, and BICC1 in the prefrontal cortex (PFC) were analyzed.</div></div><div><h3>Results</h3><div>We found that HSP90, HIF1α, and BICC1 were significantly increased in the serum of depressed patients, especially in those with recurrent depression, indicating that these molecules may serve as specific pathogenetic risk factors for depression, especially depression recurrence. In addition, the recurrent depression mice model was found to be accompanied by a significant increase in expression of HSP90, HIF1α and BICC1 in the PFC.</div></div><div><h3>Conclusions</h3><div>The current study identified HSP90, HIF1α, and BICC1 as novel potential risk factors that affect susceptibility to recurrent depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111374"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101428","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":"Myricetin alleviates learning and memory deficits in trimethyltin Alzheimer’s phenotype via attenuating hippocampal endoplasmic reticulum stress and regulating inflammation and oxidative stress","authors":"Zahra Asgari ,&nbsp;Saeid Iranzadeh ,&nbsp;Mehrdad Roghani","doi":"10.1016/j.brainresbull.2025.111382","DOIUrl":"10.1016/j.brainresbull.2025.111382","url":null,"abstract":"<div><div>Trimethyltin hydrochloride (TMT) induces hippocampal neurodegeneration and learning and memory impairments, providing a useful experimental model for Alzheimer's disease (AD) research. This study aimed to explore the neuroprotective effects of myricetin, a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, against TMT-induced hippocampal damage and elucidate some of its underlying molecular mechanisms. Male NMRI mice (n = 32) were divided into four experimental groups: control, control + myricetin, TMT, and TMT + myricetin. Neurodegeneration was induced by intraperitoneal TMT injection (2.8 mg/kg), followed by daily oral administration of myricetin (25 mg/kg) for 21 days. Learning and memory-related function was assessed using passive avoidance, novel object recognition, and Y-maze tests. After behavioral tasks, hippocampal levels of oxidative stress parameters (glutathione (GSH), superoxide dismutase (SOD), catalase, malondialdehyde (MDA)), inflammatory markers (tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10)), and endoplasmic reticulum stress pathway proteins (GRP78, PERK, IRE1α, and CHOP) were evaluated. Histological examinations included Nissl staining to quantify neuronal degeneration in CA1 and dentate gyrus regions, as well as glial fibrillary acidic protein (GFAP) immunohistochemistry. Myricetin treatment attenuated TMT-induced learning and memory impairments and neuronal loss in the CA1 and dentate gyrus subfields. It significantly enhanced hippocampal levels of GSH, SOD and catalase activities, and IL-10 while reducing levels of MDA, TNF-α, and GFAP immunoreactivity. Moreover, myricetin alleviated the TMT-induced elevation of GRP78, PERK, IRE1α, and CHOP. These findings suggest that myricetin holds promise as a therapeutic candidate for AD and other neurodegenerative disorders by counteracting oxidative stress, suppressing neuroinflammation, and modulating endoplasmic reticulum stress pathways.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111382"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092826","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":"Incorporation of graphene oxide into collagenous biomaterials attenuates scar-forming phenotype transition of reactive astrocytes in vitro","authors":"Kest Verstappen ,&nbsp;Alexey Klymov ,&nbsp;Paula A.A.P. Marques ,&nbsp;Sander C.G. Leeuwenburgh ,&nbsp;X. Frank Walboomers","doi":"10.1016/j.brainresbull.2025.111380","DOIUrl":"10.1016/j.brainresbull.2025.111380","url":null,"abstract":"<div><div>The integrin-mediated interaction between collagen type I and reactive astrocytes was recently shown to induce a detrimental, scar-forming phenotype transformation following spinal cord injury (SCI), which severely limits the therapeutic potential of commonly used collagen-based biomaterials. Graphene oxide (GO) is a promising candidate to disrupt the collagen-integrin interaction, since it is capable of altering the surface topography of biomaterials applied as SCI treatment. Moreover, free GO contributes towards potassium and glutamate transport, which is often implicated following SCI. However, it remains unclear whether both the integrin-mediated binding and astrocytic transport of potassium and glutamate are affected by GO, when inserted into collagenous biomaterials. Therefore, in the current study GO was incorporated into collagen-based hydrogels in an attempt to prevent the scar-forming phenotype transition and promote the expression of astrocytic potassium channels and glutamate transporters. Primary astrocytes were cultured either on top of or embedded within GO-enriched collagen type I or adipose tissue-derived extracellular matrix (ECM) gels. The impact of GO incorporation on integrin β1-mediated binding, astrocyte phenotype and potassium and glutamate transport was assessed by gene expression analysis and immunofluorescence studies. Upon GO incorporation into ECM gels, expression of integrin β1 and N-cadherin was significantly decreased. Moreover, GO decreased proteoglycan-associated gene expression by four-fold. Finally, GO incorporation led to a decrease in expression of both potassium channels and glutamate transporters. In conclusion, the incorporation of GO into collagen-based materials attenuated the transition of reactive astrocytes into a scar-forming phenotype.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111380"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092825","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":"Retraction notice to “Brain endothelial CD200 signaling protects brain against ischemic damage” [Brain Res. Bull. 207 (2024) 110864]","authors":"Afzal Misrani,&nbsp;Conelius Ngwa,&nbsp;Abdullah Al Mamun,&nbsp;Romana Sharmeen,&nbsp;Kanaka Valli Manyam,&nbsp;Rodney M. Ritzel,&nbsp;Louise McCullough,&nbsp;Fudong Liu","doi":"10.1016/j.brainresbull.2025.111384","DOIUrl":"10.1016/j.brainresbull.2025.111384","url":null,"abstract":"","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111384"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092828","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":"Interpreting the rich dialogue between astrocytes and neurons: An overview in Rett syndrome","authors":"Francesca M. Postogna,&nbsp;Ottavia M. Roggero,&nbsp;Fabio Biella,&nbsp;Angelisa Frasca","doi":"10.1016/j.brainresbull.2025.111386","DOIUrl":"10.1016/j.brainresbull.2025.111386","url":null,"abstract":"<div><div>Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females, with an incidence of 1 in 10,000 live births. It is caused mainly by <em>de novo</em> mutations in the X-linked <em>MECP2</em> gene, which encodes methyl-CpG binding protein 2 (<em>Mecp2</em>), a key epigenetic regulator. <em>MECP2</em> mutations have profound impacts on neurons, which exhibit morphological, synaptic and functional impairments. However, more recent evidence highlights a crucial role of astrocytes in RTT pathogenesis. Indeed, RTT astrocytes exhibit structural and functional impairments, failing to support neuronal growth and function through non-cell autonomous mechanisms. Studies reveal that <em>MECP2</em> deficient astrocytes secrete abnormal factors that impair neuronal growth and synaptic function. Furthermore, they show dysregulated calcium signalling, disrupted glutamate and potassium homeostasis, and increased inflammatory responses, all of which contribute to neuronal dysfunction. Understanding these neuron-astrocyte interactions may offer novel therapeutic targets for RTT. In the review we aim at presenting the current knowledge of astrocyte-neuron crosstalk in RTT, describing the different mechanisms highlighted so far through which <em>MECP2</em> mutant astrocytes impair neurons. Finally, we discuss existing and prospective methodological approaches for investigating cell-to-cell communication in RTT.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"227 ","pages":"Article 111386"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069595","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":"MicroRNA-669f-5p targeting deoxycytidinephosphate deaminase contributes to sevoflurane-induced cognitive impairments in aged mice via the TLR2/4–MyD88–NF-κB pathway","authors":"Yuanping Zhong ,&nbsp;Chao Zhang ,&nbsp;Yuan Li ,&nbsp;Dongqin Chen ,&nbsp;Chunchun Tang ,&nbsp;Xue Zheng ,&nbsp;Zhaoqiong Zhu","doi":"10.1016/j.brainresbull.2025.111381","DOIUrl":"10.1016/j.brainresbull.2025.111381","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a common complication associated with sevoflurane anaesthesia in the aged population. MicroRNAs have been implicated in sevoflurane-induced cognitive deficits; however, the role and underlying mechanism of microRNA (miR)-669f-5p remain unclear.</div></div><div><h3>Methods</h3><div>Eighteen-month-old mice and mouse hippocampal neurons (HT22) were exposed to sevoflurane. Cognitive function was assessed using the Morris water maze test. Neuroapoptosis and cellular proliferation were evaluated by terminal-deoxynucleotidyl transferase-mediated nick end-labelling staining and Cell Counting Kit-8 assays, respectively. The downstream molecular mechanisms of miR-669f-5p were investigated using bioinformatics analysis, western blotting, quantitative real-time polymerase chain reaction, immunofluorescence and dual-luciferase reporter assays.</div></div><div><h3>Results</h3><div>Bioinformatics analysis of the Gene Expression Omnibus database revealed upregulation of miR-669f-5p in hippocampal tissue from mice with POCD. Inhibition of miR-669f-5p substantially improved sevoflurane-induced cognitive impairment in aged mice. Deoxycytidinephosphate deaminase (Dctd) was identified as a direct target of miR-669f-5p. Overexpression of Dctd reversed the effects of miR-669f-5p mimics on apoptosis and proliferation in HT22 cells and suppressed activation of the TLR2/4–MyD88–NF-κB signalling pathway. Moreover, Dctd overexpression ameliorated sevoflurane-induced cognitive impairment in aged mice.</div></div><div><h3>Conclusion</h3><div>MicroRNA-669f-5p contributes to sevoflurane-induced cognitive impairment in aged mice by targeting Dctd and activating the TLR2/4–MyD88–NF-κB pathway. These findings provide new insights into potential therapeutic strategies for anaesthesia-related POCD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"228 ","pages":"Article 111381"},"PeriodicalIF":3.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085982","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}