{"title":"Neuroprotection effect of HSV-1 LAT-derived miR-H2 and miR-H3 associated with Tau and alpha-synuclein downregulation","authors":"Fatemeh Saadatpour , Zahra Fekrirad , S. Mohammadhadi Mirab , Pedram Mardani , Ehsan Arefian","doi":"10.1016/j.brainresbull.2025.111506","DOIUrl":"10.1016/j.brainresbull.2025.111506","url":null,"abstract":"<div><div>Latency-associated transcript (LAT)-derived miRNAs are presumably the primary anti-apoptotic impellers and the other <em>herpes simplex virus-1</em> (<em>HSV-1</em>) genes. However, the mechanisms by which this group of miRNAs negatively regulates apoptosis have not been fully elucidated. This study evaluated the hypothesis that LAT-derived miRNAs, specifically miR-H2 and miR-H3, serve as key regulatory effectors of LAT-mediated neuronal protection by targeting <em>MAPT</em> and <em>SNCA</em>, thereby interfering with caspase activation and apoptosis pathways. In silico analyses, along with in vitro and in vivo experiments, were conducted to identify key target genes of LAT-derived miR-H3 and miR-H2 and to evaluate their regulatory effects on <em>MAPT</em> and <em>SNCA</em> in sub-stable SH-SY5Y cells and latently <em>HSV-1</em>–infected mice, using quantitative real-time PCR (qRT-PCR) and Western blotting. The individual roles of miR-H2 and miR-H3 were investigated in vitro using luciferase reporter assays and a loss-of-function approach involving miRNA sponges. Additionally, the neuroprotective effects of LAT-derived miR-H2 and miR-H3 were evaluated through MTT and LDH assays, flow cytometry, and a quantitative analysis of apoptosis gene expression. It has been demonstrated that miR-H2 and miR-H3 overexpression directly target and suppress the expression of MAPT and SNCA genes, reducing their protein levels in the stable SH-SY5Y cells and during latency in TGs and Hip samples of mice. In addition, conditional miRNA sponge and luciferase assay approaches indicated the potential capacity of miR-H2 and miR-H3 to regulate <em>MAPT</em> and <em>SNCA</em> expression. Cells expressing miR-H2 and miR-H3 demonstrated an 80 % increase in viability and over 40 % enhancement in cell cycle progression, linked to the downregulation of <em>MAPT</em> and <em>SNCA</em> in SH-SY5Y cells. Significant alterations in <em>CASP3</em> and <em>BCL2</em> expression were observed in both cellular and mouse models, underscoring the anti-apoptotic effects associated with the negative regulation of caspase cascade inducers, Tau and α-syn, by miR-H2 and miR-H3. Considering the results, the neural survival prompted by LAT-derived miRNAs suggests a positive correlation between the disruption of <em>MAPT</em> and <em>SNCA</em> expression, affecting both anti-apoptotic and pro-apoptotic processes. Future studies investigating the neuroprotective properties of <em>HSV-1</em> miRNAs, particularly their impact on multi-structural peptide deficiencies, will offer valuable insights into <em>HSV-1</em>–host co-evolution and mechanisms for counteracting neuronal apoptosis. In addition to endogenous miRNAs, LAT-derived miRNAs should also be regarded as promising candidates with significant therapeutic potential for managing the molecular mechanisms underlying disorders that lead to the onset and progression of neurodegeneration.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111506"},"PeriodicalIF":3.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815766","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}
Daniel Perez-Perez , Iris A. Feria-Romero , Luis Bautista-Orozco , Walter Besio , Luisa Rocha , Angelica Vega-Garcia , Omar García-Gómez , Sandra Orozco-Suarez
{"title":"Transcranial Focal Stimulation modifies genetic expression in the cerebral cortex of naive rats","authors":"Daniel Perez-Perez , Iris A. Feria-Romero , Luis Bautista-Orozco , Walter Besio , Luisa Rocha , Angelica Vega-Garcia , Omar García-Gómez , Sandra Orozco-Suarez","doi":"10.1016/j.brainresbull.2025.111496","DOIUrl":"10.1016/j.brainresbull.2025.111496","url":null,"abstract":"<div><div>Transcranial Focal Stimulation (TFS) is an alternating-current Transcranial Electrical Stimulation technique with significant therapeutic potential. Nevertheless, the biological mechanisms responsible for the effects of TFS remain unknown. Using microarray technology, we evaluated the cerebral cortex transcriptome of rats receiving a short course (5 min) of TFS. After differential gene expression and enrichment analyses, we selected candidate genes of interest for further validation. Cerebral and hippocampal tissue of rats submitted to the same therapy were used for Western blot and immunohistochemistry to detect chosen proteins. Sham-stimulated rats were used as a reference. No differential gene expression was identified when analyzing hippocampal data. In the cerebral cortex samples, we found a total of 284 differentially expressed genes. We observed an increase in Sema4G proteins in the cerebral cortex and hippocampus (p < 0.001), and an increased expression of ZEB2 only in the hippocampus. Transcranial Focal Stimulation also increased c-Fos expression in the cerebral cortex, hippocampus, basolateral amygdala, and ventromedial hypothalamic nucleus (p < 0.001). <strong>Conclusion</strong>: A short course of TFS modifies the brain´s gene and protein expression profiles. The effects were more pronounced in the cerebral cortex than in the hippocampus. TFS also produces an increase in brain activity in cortical and subcortical regions. Additional research is necessary to validate our findings and evaluate the long-term effects of TFS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111496"},"PeriodicalIF":3.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811830","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}
Kuijun Wu , Lingyun Gao , Zhao Feng , Ioannis Kakkos , Chuantao Li , Yu Sun
{"title":"Multimodal brain network analysis reveals divergent dysconnectivity patterns during mental fatigue: A concurrent EEG-fMRI study","authors":"Kuijun Wu , Lingyun Gao , Zhao Feng , Ioannis Kakkos , Chuantao Li , Yu Sun","doi":"10.1016/j.brainresbull.2025.111505","DOIUrl":"10.1016/j.brainresbull.2025.111505","url":null,"abstract":"<div><div>For the apparent importance of mental fatigue in neuroergonomics, continuous efforts have been made to reveal the underlying neural mechanisms. Using concurrent EEG-fMRI network analysis, this work aims to reveal fatigue-related brain network reorganization. Specifically, multimodal neuroimaging data were acquired from 35 healthy participants during a 15-min sustained attention task (i.e., psychomotor vigilance task). A monotonically decreasing pattern of behavioral performance was revealed where the first and last 3-min windows were determined as the most vigilant and fatigued states. Multimodal brain network architectures within these two states were then quantitatively compared. We found that EEG and fMRI networks exhibited divergent yet interrelated reorganizations. Specifically, MF-related deficiency in parallel information transmission was revealed in multiple EEG frequency bands, yet only local efficiency was altered in fMRI networks. Moreover, a convergent decrease of nodal efficiency mainly resided in the default mode network was found in both EEG and fMRI networks, indicating a decline in cognitive control capacity during mental fatigue. Overall, by integrating multimodal EEG-fMRI network analyses, this work provides novel insights into the dynamic neural adaptations to mental fatigue, enhancing our understanding of the underlying neural mechanisms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111505"},"PeriodicalIF":3.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811829","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}
Chao Yang , Junhua Mei , Xinhua Song , Jinzhen Jiang , Cancheng Li , Anan Ping , Xingke Wang , Shaodi Wang , Sheng Yang , Yingchao Jiang , Kun Wang , Yushan Bian , Yan Wang , Guohua Chen , Changming Wang , Xiaoli Li
{"title":"The effect of hypervigilance on visual working memory in insomnia disorder: Evidence from ERP study","authors":"Chao Yang , Junhua Mei , Xinhua Song , Jinzhen Jiang , Cancheng Li , Anan Ping , Xingke Wang , Shaodi Wang , Sheng Yang , Yingchao Jiang , Kun Wang , Yushan Bian , Yan Wang , Guohua Chen , Changming Wang , Xiaoli Li","doi":"10.1016/j.brainresbull.2025.111503","DOIUrl":"10.1016/j.brainresbull.2025.111503","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates the impact of hypervigilance on visual working memory in individuals with insomnia disorder using event-related potentials (ERP) and time-frequency analysis.</div></div><div><h3>Methods</h3><div>A total of 45 insomnia disorder (ID) patients and 43 healthy controls (HC) participated in a visual working memory task that involved encoding, maintaining, and retrieving visual stimuli (S1 and S2) of blurred and clear pictures. ERP components and frequency bands were analyzed across these stages.</div></div><div><h3>Results</h3><div>The ID group had significantly altered ERP amplitudes and increased theta and beta activity across all stages compared to the HC group, indicating hypervigilance and cognitive resource consumption during working memory processing. In the encoding stage, P100 and N170 amplitudes were significantly correlated with insomnia severity (ISI), while P200 amplitude was linked to HAMA score. During the maintenance stage, CNV amplitude and increased theta power were associated with sustained attention, which correlated with ISI scores, reflecting the burden of maintaining attention in hypervigilance states. In the retrieval stage, the ID group showed reduced P300 amplitudes but increased LPC amplitudes, highlighting their struggle with memory updating and complex cognitive processing under hypervigilance states.</div></div><div><h3>Conclusion</h3><div>These findings suggest that ID patients exhibit hypervigilance, which affects the efficiency of visual working memory, impairs attention regulation, and increases cognitive load during tasks. Understanding these mechanisms may provide insights for clinical interventions aimed at improving cognitive function in ID patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111503"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793544","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}
Yingxue He , Yanjing Guo , Xiaowei Li , Jiangnan Wu , Zunsai Feng , Gongming Wang , Mengyuan Zhang
{"title":"Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway","authors":"Yingxue He , Yanjing Guo , Xiaowei Li , Jiangnan Wu , Zunsai Feng , Gongming Wang , Mengyuan Zhang","doi":"10.1016/j.brainresbull.2025.111497","DOIUrl":"10.1016/j.brainresbull.2025.111497","url":null,"abstract":"<div><div>Sevoflurane is a widely used anesthetic in elderly patients and has been linked to postoperative cognitive dysfunction; however, its molecular mechanisms remain unclear. Inhibition of adult hippocampal neurogenesis (AHN) and epigenetic alterations, particularly via histone deacetylase 8 (HDAC8), have emerged as potential contributors to these deficits. Using young and aged C57BL/6 J male mice exposed to varying sevoflurane concentrations, we evaluated cognitive function and AHN. High-concentration (3 %) sevoflurane impaired both cognition and AHN in aged mice, correlating with reduced histone acetylation, increased HDAC8 expression, and diminished pCREB/BDNF signaling. Notably, HDAC8 inhibition with PCI-34051 or direct BDNF administration reversed these effects, while HDAC8 overexpression recapitulated the deficits. These findings suggest that HDAC8 upregulation is a key mediator of sevoflurane-induced cognitive decline via AHN suppression, highlighting a promising therapeutic target for anesthesia-related neurotoxicity.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111497"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783562","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":"Volume analysis of hippocampus and amygdala subregions in patients with retinal detachment","authors":"Yuanyuan Wang, Feng Ouyang, Jie Liu, Zihe Xu, Lianjiang Lv, Meimei Yan, Jialu Chen, Zhijun Luo, Xianjun Zeng","doi":"10.1016/j.brainresbull.2025.111498","DOIUrl":"10.1016/j.brainresbull.2025.111498","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to investigate the pattern of atrophy in the hippocampus and amygdala subregions in patients with retinal detachment (RD) and its correlation with cognition and emotion.</div></div><div><h3>Methods</h3><div>The study recruited 32 patients diagnosed with RD alongside 33 healthy controls (HCs), carefully matched for sex and age. Magnetic resonance imaging (MRI) scans of all participants underwent automated segmentation to delineate hippocampal and amygdala subfields, utilizing FreeSurfer v6.0.</div></div><div><h3>Results</h3><div>In contrast to the HCs, RD patients exhibited noteworthy volumetric reductions in various regions, including cornu ammonis 1 (CA1)-head, molecular layer, dentate gyrus, and hippocampus-amygdala transition area bilaterally. This led to a collective decrease in the volume of the bilateral whole hippocampal head, right whole hippocampal body, and right entire hippocampus. In addition, the volume of Accessory-Basal-nucleus, Anterior-amygdaloid-area-AAA, and Corticoamygdaloid-transitio on the right side was also significantly reduced. Furthermore, the decrease in hippocampal and amygdala subfield volumes among RD patients showed a negative correlation with disease duration and HAMA score, while exhibiting a positive correlation with the axial length of eye and MoCA score.</div></div><div><h3>Conclusion</h3><div>These findings imply that alterations in the volume of hippocampal and amygdala subfields in RD patients are associated with emotional and cognitive dysfunction and may serve as biomarkers for predicting disease progression in RD patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111498"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774711","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":"METTL14 promotes hippocampal neuronal cuproptosis via m6A modification on FDX1 mRNA in cerebral ischemia-reperfusion injury","authors":"Wanqiu Ding, Hongmei Gao, Ruijia Liu, Hanshu Zhao, Sihan Liu, Jinru Shen, Xinyue Zhao, Yuanqi Xu, Zhongling Zhang","doi":"10.1016/j.brainresbull.2025.111504","DOIUrl":"10.1016/j.brainresbull.2025.111504","url":null,"abstract":"<div><h3>Objective</h3><div>Cuproptosis, a consequence of excessively high copper concentrations, is considered a potential therapeutic target for cerebral ischemia-reperfusion injury (IRI). Methyltransferases are key modulators of cuproptosis through N6-methyladenosine (m<sup>6</sup>A) modification on ferredoxin 1 (FDX1) mRNA. This study aims to determine whether methyltransferase-like 14 (METTL14) regulates cuproptosis in cerebral IRI <em>via</em> m<sup>6</sup>A modification on FDX1 mRNA.</div></div><div><h3>Methods</h3><div>The middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice, and oxygen glucose deprivation/reoxygenation-treated mouse primary hippocampal neurons were used to mimic cerebral IRI <em>in vivo</em> and <em>in vitro</em>, respectively. The functional role of METTL14 in cerebral IRI was determined by examining neurological functions, cerebral infarction, hippocampal CA1 tissue changes, neuronal viability, and cuproptosis using knockdown experiments. The involvement of FDX1 in the METTL14 regulatory pathway was verified by overexpressing FDX1.</div></div><div><h3>Results</h3><div>METTL14 expression was increased in the hippocampal tissue of mice subjected to MCAO/R. METTL14 knockdown reduced neurological deficits, infarct size, and hippocampal CA1 neuronal cuproptosis in MCAO/R mice. Furthermore, activation of hippocampal CA1 neuronal cuproptosis partly averted the alleviation of cerebral IRI by METTL14 knockdown. These results were reproduced in <em>in vitro</em> studies. Furthermore, mechanistic studies revealed that METTL14 knockdown reduced the stability of FDX1 mRNA through m<sup>6</sup>A modification and consequently limited FDX1 expression. Importantly, FDX1 overexpression could partly reverse the cuproptosis inhibition induced by METTL14 knockdown.</div></div><div><h3>Conclusion</h3><div>Taken together, this research innovatively demonstrates the neuroprotective effect of METTL14 knockdown on hippocampal CA1 neurons in cerebral IRI <em>via</em> its regulation of FDX1, which might help design new therapies to improve cerebral IRI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111504"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793543","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}
Xiulin Liang, Qinghua Zhang, Chuanlong Zhang, Jingjing Liu, Pengcheng Sang, Qing Mao, Lei Wang
{"title":"Reconfiguration of dynamic brain networks in heart failure with preserved ejection fraction: Linking neurovascular coupling and cardiac dysfunction","authors":"Xiulin Liang, Qinghua Zhang, Chuanlong Zhang, Jingjing Liu, Pengcheng Sang, Qing Mao, Lei Wang","doi":"10.1016/j.brainresbull.2025.111500","DOIUrl":"10.1016/j.brainresbull.2025.111500","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to investigate the alterations in static and dynamic network topology properties in patients with heart failure with preserved ejection fraction (HFpEF).</div></div><div><h3>Methods</h3><div>Functional magnetic resonance imaging (fMRI) was obtained from 41 patients with HFpEF and 39 healthy individuals. The topology properties of static and dynamic functional brain networks were examined using graph theory methodologies, and the correlation between abnormal brain network characteristics and clinical features was assessed.</div></div><div><h3>Results</h3><div>(1) Static network topology properties exhibited significantly decreased local network efficiency among patients with HFpEF. The connectivity strength and information processing efficiency were diminished in the left parahippocampal gyrus, left cingulate gyrus, and right insular gyrus brain regions, and improved in the left thalamus, right fusiform gyrus, and right precuneus regions. (2) Dynamic network topology properties of patients with HFpEF showed decreased variability in critical nodes and brain subregions (e.g., the superior frontal gyrus, left amygdala, and left fusiform gyrus) and compensatory increases in the variability of specific regions (e.g., right insular gyrus, right postcentral gyrus, and right temporal gyrus). (3) In HFpEF, the static and dynamic functional brain network topology properties of the fusiform gyrus, cingulate gyrus, superior temporal gyrus, precuneus, parahippocampal gyrus, insular gyrus, and amygdala regions were significantly correlated with cardiac structural and functional indices, such as LVDd, LVMI, and E/e′ ratio.</div></div><div><h3>Conclusion</h3><div>Alterations in cardiac structure and function in HFpEF may affect the dynamic activity of specific brain networks through neurovascular coupling mechanisms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111500"},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144766951","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}
Yan Li , Rui Xiao , Jie Yang , Hongfu Dan, Hengping Wu, Limei Han, Zhongqin Liu, Jianquan Zhong, Hao Feng
{"title":"Preliminary study of multiple diffusion MRI in defining brain microstructural changes in hypertensive individuals","authors":"Yan Li , Rui Xiao , Jie Yang , Hongfu Dan, Hengping Wu, Limei Han, Zhongqin Liu, Jianquan Zhong, Hao Feng","doi":"10.1016/j.brainresbull.2025.111499","DOIUrl":"10.1016/j.brainresbull.2025.111499","url":null,"abstract":"<div><h3>Purpose</h3><div>to use multiple diffusion models to characterize the microstructural changes in the brains of patients with hypertension.</div></div><div><h3>Methods</h3><div>This study included 35 healthy controls (HC), 21 patients with untreated hypertension, and 25 patients with medically treated hypertension. All subjects underwent both routine MRI and diffusion spectrum imaging (DSI). DSI were reconstructed to obtain diffusion MRI models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator-MRI (MAP-MRI). Tract-based spatial statistics (TBSS) were used to analyze the parameters among the three groups. Depending on the type of data, the proper statistical tests were used.</div></div><div><h3>Results</h3><div>No statistically significant differences were observed between the HC group and the treated group. The untreated group showed considerably lower fractional anisotropy (FA) values than the HC group in almost all white matter areas. Significantly higher mean diffusivity (MD) and radial diffusivity (RD) values were seen in the untreated group. The untreated group exhibited considerably greater extracellular volume fraction (ECVF) values of the white matter. Compared to the differences found between the HC and untreated groups, the differences in multiple derived-parameters of NODDI and MAP-MRI were comparatively less between the treated and untreated groups. Strong positive associations were seen between the systolic pressure and the ECVF values of multiple brain regions.</div></div><div><h3>Conclusions</h3><div>NODDI and MAP-MRI derived-parameters are more sensitive to brain white matter injury in hypertension. The ECVF readings of the NODDI may more accurately represent white matter damage linked to hypertension.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111499"},"PeriodicalIF":3.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144766952","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":"Metal-organic framework UiO-66 dose-dependently mitigates oxidative stress and astrocyte activation in the rat hippocampus","authors":"Ali Dankoob , Moein Shirzad , Fatemeh Rabiei , Hamid Askari , Shahram Ghasemi , Aliakbar Rajabzadeh , Maryam Ghasemi-Kasman","doi":"10.1016/j.brainresbull.2025.111494","DOIUrl":"10.1016/j.brainresbull.2025.111494","url":null,"abstract":"<div><div>Although the metal-organic framework (MOF) UiO-66 is used as a drug delivery system, its potential harmful effects on the nervous system remain underexplored. This study evaluated the subacute impact of UiO-66 nanoparticles on working and spatial memory, neuronal integrity, oxidative stress, and astrocyte activation in the rat hippocampus. Fifty-six Wistar rats were randomly assigned to four groups. The control group received intravenous injections of normal saline, while the treatment groups were administered UiO-66 at doses of 1, 10, or 50 mg/kg over two weeks (four injections, twice weekly). After the final injection, the animals were subjected to behavioral assessments via the Morris water maze, Y-maze test, novel arm discrimination test (NADT), and novel object recognition test (NORT). Subsequently, brain samples were collected for histological and biochemical analyses. Behavioral evaluations revealed no significant differences in learning, working memory, or spatial memory among the groups. The NADT and NORT data revealed recognition memory deficits at the highest UiO-66 dose. However, biochemical assays demonstrated a dose-dependent increase in free radical production with increasing UiO-66 doses. Histopathological examinations revealed dose-related neuronal alterations, including cellular fragmentation, vacuolization, and tissue disarray. Moreover, GFAP immunostaining confirmed significant astrocyte activation in the hippocampus at higher doses, which was correlated with increased neuronal damage and cell death. Overall, while subacute exposure to UiO-66 nanoparticles at lower doses did not markedly impair cognitive performance, higher concentrations of UiO-66 were associated with elevated oxidative stress, histopathological damage, increased neuronal loss, and astrocyte activation in the brains of the rats.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111494"},"PeriodicalIF":3.7,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757647","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}