Brain Research Bulletin最新文献

{"title":"Reversal of auditory cortical hyperexcitability and restoration of synaptic plasticity balance by GluN1-mediated photobiomodulation in noise-induced tinnitus","authors":"Zhixin Zhang ,&nbsp;Xinmiao Xue ,&nbsp;Dongdong He ,&nbsp;Peng Liu ,&nbsp;Chi Zhang ,&nbsp;Yvke Jiang ,&nbsp;Shuhan Lv ,&nbsp;Li Wang ,&nbsp;Hanwen Zhou ,&nbsp;Weidong Shen ,&nbsp;Shiming Yang ,&nbsp;Fangyuan Wang","doi":"10.1016/j.brainresbull.2025.111685","DOIUrl":"10.1016/j.brainresbull.2025.111685","url":null,"abstract":"<div><div>Glutamate receptors regulate neuronal excitability and drive synaptic plasticity in the auditory cortex (AC), with aberrant activation or dysfunction contributing to tinnitus pathogenesis. Photobiomodulation (PBM) exerts sustained modulatory effects on neural activity and behavioral responses across species, including humans. However, its therapeutic potential and mechanisms in noise-induced tinnitus remain unexplored. Here, we developed a noninvasive low-irradiance PBM device to target the AC of animal models, investigating near-infrared light mechanisms for reversing cortical hyperexcitability and restoring synaptic plasticity. In noise-exposed tinnitus models without significant neuronal loss, we observed abnormally elevated GluN1 activation and increased synaptic structural complexity compared to non-tinnitus or sham-exposed controls. Tinnitus models were subjected to PBM interventions with varying parameters (irradiance power: 20/40/80 mW/cm²; exposure duration: 300/600 s). Therapeutic efficacy was validated through auditory brainstem response (ABR), gap-prepulse inhibition of acoustic startle (GPIAS), and prepulse inhibition (PPI) behavioral assays. Fluorescence microscopy of brain sections quantified c-Fos/GluN1 co-localization to image activated NMDARs, while Nissl staining assessed PBM safety across parameters. Phosphoproteomic profiling explored mechanistic pathways, with neuronal morphological changes visualized via Golgi staining and transmission electron microscopy. To confirm GluN1’s pivotal role in auditory cognition, we engineered transgenic mice with GluN1 overexpression or knockdown. GluN1-overexpressing mice exhibited tinnitus-like behaviors at specific frequencies, whereas GluN1-deficient tinnitus models showed aberrant behaviors due to impaired auditory cognition. Our findings delineate noise-induced tinnitus mechanisms and PBM-mediated regulation of neuronal excitability and structural plasticity, establishing an irradiance-duration optimization framework for clinical translation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111685"},"PeriodicalIF":3.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773670","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":"Peripheral CD200R signaling: A critical regulator of post-stroke inflammation in aged mice","authors":"Conelius Ngwa,&nbsp;Afzal Misrani,&nbsp;Yan Xu,&nbsp;Jingjing Wang,&nbsp;Rodney Ritzel,&nbsp;Fudong Liu","doi":"10.1016/j.brainresbull.2025.111686","DOIUrl":"10.1016/j.brainresbull.2025.111686","url":null,"abstract":"<div><div>The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16–19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then subjected to a 45-min transient middle cerebral artery occlusion (MCAO). At three days post-stroke, flow cytometry, ELISA, and immunohistochemistry (IHC) were used to assess immune responses. Infarct volumes and neurobehavioral deficits were also evaluated. We found that T cell infiltration into the brain was significantly greater in KO-to-GFP (central CD200R signaling) compared to GFP-to-KO (peripheral CD200R signaling) mice. KO-to-GFP mice also exhibited significantly higher levels of pro-inflammatory cytokines IL-1β and TNF-α in the ischemic brain than GFP-to-KO chimeras. Correspondingly, KO-to-GFP mice showed significantly larger brain infarct volumes and worse neurobehavior deficits compared to GFP-to-KO chimeras. Together, these findings indicate that the peripheral (not the central) CD200R signaling plays a critical role in controlling post-stroke immune responses and delineating ischemic injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111686"},"PeriodicalIF":3.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762302","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":"Effects of repetitive transcranial magnetic stimulation on apoptosis and MAPK/PI3K-AKT signaling pathways in rats with spinal cord injury","authors":"Qingqin Xu ,&nbsp;Junhong Su ,&nbsp;Qian Lei ,&nbsp;Jinxiu Liu ,&nbsp;Jing Wang ,&nbsp;Mengyu Yang ,&nbsp;Juan Song ,&nbsp;Hemu Chen ,&nbsp;Jianwei Lu","doi":"10.1016/j.brainresbull.2025.111687","DOIUrl":"10.1016/j.brainresbull.2025.111687","url":null,"abstract":"<div><h3>Background</h3><div>Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive neuromodulation technique, but its mechanisms in spinal cord injury (SCI) remain unclear. This study investigated the effects and potential mechanisms of rTMS on motor recovery in SCI rats.</div></div><div><h3>Methods</h3><div>A rat SCI model was established using the modified Allen's method. rTMS treatment was initiated on postoperative Day 2 and administered daily for 56 days. Bioinformatics analysis was first conducted to identify SCI-related genes and signaling pathways. Western blotting, immunofluorescence staining, TUNEL assay, NeuN staining, motor evoked potential (MEP) measurement, hematoxylin-eosin staining, and Basso-Beattie-Bresnahan (BBB) score were performed to evaluate molecular and functional outcomes.</div></div><div><h3>Results</h3><div>Bioinformatics analysis identifies MAPK-, PI3K/AKT-, and Bcl-2-related genes as potentially involved in SCI pathology. Western blotting reveals that rTMS is associated with lower levels of p-JNK, p-p38 MAPK, Bax, and caspase-3, and with higher levels of p-ERK, p-PI3K, p-AKT, and Bcl-2 (<em>P</em> &lt; 0.001). Immunofluorescence staining shows that rTMS is accompanied by reduced p-JNK and p-p38 MAPK positive cells and increased p-ERK, p-PI3K and p-AKT positive cells (<em>P</em> &lt; 0.001). TUNEL and NeuN staining further suggest reduced neuronal apoptosis in the injured spinal cord. Behavioral and electrophysiological assessments show that rTMS is associated with shorter MEP latencies, higher MEP amplitudes, reduced spinal tissue damage, attenuated muscle atrophy, and improved BBB score (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>rTMS is associated with improvements in motor function and anti-apoptotic molecular changes in SCI rats, possibly via modulation of MAPK and PI3K/AKT signaling pathways, including upregulation of Bcl-2 and downregulation of Bax and caspase-3.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111687"},"PeriodicalIF":3.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762154","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":"Comparison of epilepsy mouse models induced by kainic acid through different administration routes","authors":"Li-Wei Xing ,&nbsp;Chen Yang ,&nbsp;Wenxuan Tang ,&nbsp;Yongjie Deng ,&nbsp;Wen-Xu Wang ,&nbsp;Jia-Hui Guo ,&nbsp;Xin-Yi Wang ,&nbsp;Run-Chen Fang ,&nbsp;Jian Guan ,&nbsp;Jing Cang ,&nbsp;Shi-Bin Li","doi":"10.1016/j.brainresbull.2025.111684","DOIUrl":"10.1016/j.brainresbull.2025.111684","url":null,"abstract":"<div><div>Sleep disruption associated with epilepsy is frequently observed in clinical practice. Various epilepsy animal models including the widely-used chemoconvulsant kainic acid (KA) have been developed to unveil the mechanisms underlying this life-threatening central disorder and improve sleep management. However, a systematic comparison of epilepsy models induced through different KA administration routes (intrahippocampal, IH, vs. intraperitoneal, IP) remains lacking. In this study, we monitored the dynamic changes of sleep/wake architecture, the development of epilepsy, and performed histological mapping of brain regions potentially implicated in epileptogenesis. We observed a more severe disruption of sleep architecture associated with seizures perpetuating for a longer time in the IHKA group. IHKA induced a more robust epilepsy pattern with significant increases of wakefulness and reductions of sleep during the acute phase. A chronic epilepsy model was developed in the IHKA group, but not in the IPKA group. Both IHKA and IPKA groups developed NREM sleep fragmentation during the chronic phase. Isolated spikes induced by IHKA appeared more frequently than those induced by IPKA at all time points, and gradually declined before stabilization around day 14 post-administration. Both IPKA and IHKA induced elevated c-Fos expression within 3 h after the drug administration as compared to their controls. Pearson correlation analyses of c-Fos expression across brain regions revealed that the IHKA group exhibited more correlations among multiple brain regions, reflecting a broader network of activated regions compared with the IPKA group after local KA exposure. Therefore, IHKA creates a more robust epilepsy mouse model characterized by a more fragmented sleep pattern, more seizures, and more isolated spikes.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111684"},"PeriodicalIF":3.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755139","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":"Linking VR performance to cognitive ability: The significance of ACC-PCL connectivity in aging populations","authors":"Zhen Gu ,&nbsp;Jing Cao ,&nbsp;Zhiqiang Wu ,&nbsp;Ling Yue","doi":"10.1016/j.brainresbull.2025.111681","DOIUrl":"10.1016/j.brainresbull.2025.111681","url":null,"abstract":"<div><h3>Background</h3><div>Neuropsychological tests provide standardized cognitive assessment but have limited ecological validity. Virtual reality (VR) creates immersive environments, better reflecting real-world cognitive performance. Although impaired VR performance correlates with early cognitive decline, its neural mechanisms remain unclear in non-demented elders. This study investigates fMRI biomarkers linked to VR performance to identify neural predictors of cognitive decline.</div></div><div><h3>Methods</h3><div>24 non-demented older adults, including cognitively normal (CN) and mild cognitive impairment (MCI), completed baseline resting-state fMRI and immersive VR tasks combining physical and cognitive demands (dog walking, mountain climbing, drone protection). VR performance score (VRS) was quantified via entropy weight method. We analyzed relationships between VRS, neuropsychological scores, and resting-state functional connectivity (FC).</div></div><div><h3>Results</h3><div>VRS significantly correlated with MoCA visuospatial/executive scores (p = 0.015). Whole-brain FC analysis revealed a strong association between VRS and FC between the left anterior cingulate cortex (ACC) and left paracentral lobule (PCL) in the overall sample (adjusted p = 1.94 × 10⁻⁶), present in CN but absent in MCI. Stepwise regression confirmed this FC as the significant VRS predictor in CN (R² = 0.599, p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Immersive VR performance reflects visuospatial/executive function and is predicted by left ACC-PCL connectivity, serving as a neuroimaging biomarker for real-world cognition that complements traditional assessments. Practically, this biomarker requires validation in larger longitudinal cohorts.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111681"},"PeriodicalIF":3.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734692","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":"A multimodal fusion framework reveals the heterogeneity of basal ganglia atrophy and its molecular mechanisms in temporal lobe epilepsy","authors":"Guiming Weng ,&nbsp;Xiaochuan Fu ,&nbsp;Cuimi Luo ,&nbsp;Qin Zhou ,&nbsp;Huoyou Hu ,&nbsp;Bailing Qin ,&nbsp;Binghua Lv ,&nbsp;Zirong Chen ,&nbsp;Jinou Zheng","doi":"10.1016/j.brainresbull.2025.111682","DOIUrl":"10.1016/j.brainresbull.2025.111682","url":null,"abstract":"<div><div>The heterogeneity of basal ganglia (BG) atrophy in temporal lobe epilepsy (TLE) has not been fully elucidated. This study employed a multimodal fusion framework to examine the potential heterogeneity of BG atrophy among TLE patients. 89 patients diagnosed with TLE were recruited. Structural magnetic resonance imaging (sMRI), resting - state functional magnetic resonance imaging (fMRI), consensus clustering (CC), and neuroimaging - transcriptomic approaches were integrated to explore the structural and functional alterations in the BG and their molecular mechanisms. Canonical correlation analysis (CCA) was employed to investigate the associations between MRI features and clinical characteristics. An individualized prediction model was constructed to facilitate clinical decision-making. CC identified a significant subgroups of BG atrophy in TLE: widespread BG atrophy (TLE-Cluster1, TLE-C1). In TLE-C1, the functional connectivity between the BG and cortical regions associated with sensation, emotion, and memory was notably enhanced. These patients additionally exhibited more severe cognitive impairment as well as higher degrees of anxiety and depression. Transcriptomic analysis established a connection between the heterogeneity of BG atrophy and specific gene expression patterns that were enriched in biological processes such as synaptic function, neurostructural development, and learning and memory. Further analyses uncovered a positive correlation between the gray matter volume of BG and cognitive performance. A classifier based on a Neural Network (NNET) predicted cognitive function with an area under curve (AUC) of 0.983. This study characterizes BG atrophy heterogeneity in TLE, its molecular mechanisms, and clinical relevance, offering insights for personalized diagnosis and management.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111682"},"PeriodicalIF":3.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734693","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":"Cerebellar subregional atrophy in relapsing-remitting multiple sclerosis: Stage-dependent dynamics and pharmacological modulation","authors":"Xiaohui Zhang ,&nbsp;Jinzhou Feng ,&nbsp;Zhiwei Zhang ,&nbsp;Bin Yu ,&nbsp;Silin Du ,&nbsp;Kai Zhang ,&nbsp;Xiaoya Chen ,&nbsp;Yongmei Li","doi":"10.1016/j.brainresbull.2025.111679","DOIUrl":"10.1016/j.brainresbull.2025.111679","url":null,"abstract":"<div><h3>Background</h3><div>Cerebellar atrophy is increasingly recognized as an important pathological feature of multiple sclerosis (MS). However, the specific patterns at different stages and their alteration by disease-modifying therapies (DMTs) are not well comprehended.</div></div><div><h3>Objective</h3><div>This study aimed to investigate stage-dependent cerebellar subregional volume changes in relapsing-remitting MS (RRMS) and evaluate the effects of different DMT classes on cerebellar atrophy and clinical outcomes.</div></div><div><h3>Methods</h3><div>A total of 181 patients with RRMS and 99 healthy controls were recruited for this study. Patients were stratified by lesion activity into acute-active, chronic-active, and chronic-inactive subgroups, and by pharmacological mechanism into untreated, sphingosine-1-phosphate (S1P)_T (siponimod, fingolimod, and ozanimod) and not_S1P_DMT (dimethyl fumarate and teriflunomide). Cerebellar subregional volumes were quantified using the deep learning-based tool, CerebNet. Group comparisons were conducted, and interaction effects were examined. The correlations between the cerebellar subregions and cognition were subsequently analyzed.</div></div><div><h3>Results</h3><div>In the lesion-activity subgroups, significant volume loss was detected in several posterior cerebellar lobules, including Crus II, VIIIa/b, VIIb, X, Crus I, and IX (all <em>p</em> &lt; 0.05). The acute-active subgroup exhibited additional atrophy in anterior lobules I–IV and vermis IX compared with the chronic-active subgroup (all <em>p</em> &lt; 0.05). In the treatment subgroups, widespread reductions were observed in the posterior lobules Crus I/II, V, VIIb, VIIIb, IX, and X, with most decreases appearing in the untreated groups (all <em>p</em> &lt; 0.05). Pairwise com<em>p</em>arisons displayed region-specific patterns: left VIIIa volume was reduced in the MS_noDrug and MS_not_S1P_DMT groups but increased in the S1P_DMT group, whereas right lobule V in the S1P_DMT and vermis VI in the MS_not_S1P_DMT were both higher (all <em>p</em> &lt; 0.05). The interaction effects of disease stage and treatment were mainly localized to lobules IX and VIIIb, and the volumes of bilateral IX lobules showed a weak positive correlated with cognitive performance.</div></div><div><h3>Conclusion</h3><div>This study demonstrated stage-specific patterns of cerebellar atrophy in RRMS and the heterogeneous, stage-dependent effects of DMTs on posterior cerebellar subregions. Lobules IX and VIIIb emerged as critical loci linking pharmacological modulation with cognitive outcomes. These findings suggest that these regions may serve as potential imaging biomarkers of therapeutic response and prognosis in MS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111679"},"PeriodicalIF":3.7,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713347","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":"Microstructural white matter impairments in chronic fatigue syndrome: Evidence of segmental injury in the cingulum bundle","authors":"Kang Wu ,&nbsp;Ziyao Wu ,&nbsp;Sitong Feng ,&nbsp;Tian Zhou ,&nbsp;Yanzhe Ning ,&nbsp;Kuangshi Li ,&nbsp;Hongxiao Jia","doi":"10.1016/j.brainresbull.2025.111671","DOIUrl":"10.1016/j.brainresbull.2025.111671","url":null,"abstract":"<div><h3>Background</h3><div>Chronic fatigue syndrome (CFS) is a neurological disorder characterized by persistent fatigue. Previous studies have shown structural and functional brain alterations in CFS patients. However, how chronic fatigue affects white matter remains unclear.</div></div><div><h3>Methods</h3><div>We recruited 100 CFS patients and 100 healthy controls (HCs) and collected their diffusion weighted imaging (DWI) data along with fatigue severity scores. Group comparisons were conducted using 87 white matter tract templates derived from 1068 healthy individuals to identify impaired tracts. Fiber bundle quantitative analysis was then applied to localize segmental disruptions. Furthermore, a machine learning model was developed to evaluate the importance of the identified tracts in diagnosing CFS, and treatment efficacy analysis was performed to examine the causal relationship between recovery of fiber bundle structure and improvement in fatigue symptoms.</div></div><div><h3>Results</h3><div>Compared with HCs, CFS patients exhibited reduced fractional anisotropy (FA) in the left cingulum parolfactory tract and the left cingulum frontal-parahippocampal tract. The quantitative analysis indicated that disruptions in these two tracts were localized to the middle-posterior portion of the cingulum bundle. Moreover, FA values of the two tracts yielded 85 % accuracy in distinguishing CFS patients, and causal analysis demonstrated that recovery of these segmentally disrupted tracts was associated with improvements in fatigue symptoms.</div></div><div><h3>Conclusions</h3><div>This large-sample study provides comprehensive insights into microstructural impairments induced by chronic fatigue and highlights the critical role of the cingulum bundle in the pathological mechanisms of CFS, thereby advancing our understanding of CFS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111671"},"PeriodicalIF":3.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707447","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":"CAF-derived exosomes promote the proliferation and invasion of pituitary adenoma cells via miR-184 transfer","authors":"Qiu Du ,&nbsp;Zhiyong Chen ,&nbsp;Weiyu Zhang ,&nbsp;Mengchao Zhu ,&nbsp;Zhichao Yang ,&nbsp;Yaru Li ,&nbsp;Lei Xu ,&nbsp;Jianmin Zhang ,&nbsp;Aijun Peng ,&nbsp;Qingling Feng","doi":"10.1016/j.brainresbull.2025.111678","DOIUrl":"10.1016/j.brainresbull.2025.111678","url":null,"abstract":"<div><div>Pituitary adenomas (PAs) are common intracranial tumors whose mass effects and endocrine dysfunction pose serious threats to patient health. However, the mechanisms underlying their progression, particularly the role of the tumor microenvironment (TME), remain insufficiently studied. Within this context, cancer-associated fibroblasts (CAFs) have been shown to drive tumor development via extracellular matrix remodeling and extracellular vesicle release, but their specific contributions to PA progression remain unclear. In this study, we observed a correlation between PA invasiveness and fibroblast density in the TME. Functionally, both CAFs and CAF-derived exosomes significantly enhanced the proliferation and invasion of PA cells compared to normal fibroblasts. Small RNA sequencing identified 16 upregulated and 8 downregulated miRNAs in CAF-derived exosomes, with KEGG analysis indicating enrichment in MAPK signaling, regulation of actin cytoskeleton, and lysosome-related pathways. Among these, miR-184 was notably upregulated in both CAF-derived exosomes and PA specimens. We further demonstrated that exosomal miR-184 from CAFs could be transferred into PA cells, promoting their proliferation and invasion, while miR-184 knockdown attenuated the tumor-promoting effects of CAF-derived exosomes. Mechanistically, TLE1 was validated as a direct functional target of miR-184. In summary, our study reveals exosomal miR-184 as a key mediator of CAF-driven PA progression, highlighting its potential as a therapeutic target for PAs.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111678"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695852","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":"Sodium acetate and sodium butyrate ameliorate postoperative cognitive dysfunction in aged rats by suppressing inflammation and ferroptosis via inhibition of the cGAS-STING signaling pathway","authors":"Kai-Hui Zeng ,&nbsp;Li-Ping Yu ,&nbsp;Zhen Chen ,&nbsp;Xiang Li","doi":"10.1016/j.brainresbull.2025.111677","DOIUrl":"10.1016/j.brainresbull.2025.111677","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication in elderly patients following surgery. Short-chain fatty acids (SCFAs), including acetate and butyrate, exert anti-inflammatory and antioxidant properties; however, their potential neuroprotective roles in POCD remain largely unexplored. Hence, this study investigated whether sodium acetate (NaA) and sodium butyrate (NaB) ameliorate POCD in aged rats and elucidated the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A POCD model was established in aged male Sprague-Dawley rats by exploratory laparotomy under isoflurane anesthesia. NaA or NaB was administered orally prior to surgery. Cognitive function was assessed using the Morris water maze (MWM), Y-maze, and novel object recognition (NOR) tests. Hippocampal inflammatory responses were assessed by measuring TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. Ferroptosis was evaluated by measuring reactive oxygen species (ROS), malondialdehyde (MDA), Fe²⁺ content, antioxidant activities (SOD, GPx, GSH), and the expression of ferroptosis-related genes (TfR1, DMT1, FTH1, FTL, GPX4, and SLC7A11). Activation of the cGAS-STING signaling pathway was examined via Western blot and ELISA. In addition, hippocampal cGAS was overexpressed to assess its causal role.</div></div><div><h3>Results</h3><div>Both NaA and NaB significantly improved cognitive performance in aged POCD rats, as evidenced by enhanced spatial learning and memory in the MWM, increased spontaneous alternation in the Y-maze test, and a higher recognition index in the NOR test. Mechanistically, NaA and NaB markedly suppressed hippocampal inflammation, as evidenced by decreased TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. NaA and NaB also attenuated ferroptosis, indicated by decreased ROS, MDA, and Fe²⁺ levels, restored SOD, GPx, and GSH activities, upregulated GPX4, SLC7A11, FTH1, and FTL expression, and downregulated TfR1 and DMT1 expression in the hippocampus of aged POCD rats. Furthermore, NaA and NaB inhibited activation of the cGAS-STING signaling pathway in the hippocampus of aged POCD rats. Importantly, hippocampal cGAS overexpression reversed the anti-inflammatory, anti-ferroptotic, and cognitive protective effects of NaA and NaB.</div></div><div><h3>Conclusion</h3><div>NaA and NaB ameliorate POCD in aged rats by mitigating hippocampal inflammation and ferroptosis, potentially via inhibition of the cGAS-STING signaling pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111677"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699625","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}