Brain ResearchPub Date : 2025-05-24DOI: 10.1016/j.brainres.2025.149735
Minerva Ortiz-Valladares , Christian Peregrino-Ramírez , Ricardo Pedraza-Medina , Jorge Guzmán-Muñiz , Oscar Gonzalez-Perez
{"title":"Sex-specific effects of chronic fluoxetine on c-Fos expression in Murine brain regions","authors":"Minerva Ortiz-Valladares , Christian Peregrino-Ramírez , Ricardo Pedraza-Medina , Jorge Guzmán-Muñiz , Oscar Gonzalez-Perez","doi":"10.1016/j.brainres.2025.149735","DOIUrl":"10.1016/j.brainres.2025.149735","url":null,"abstract":"<div><div>Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely prescribed for treating mood disorders. Despite its therapeutic benefits, the precise mechanisms and brain regions impacted by long-term FLX treatment remain understood. To explore this, we analyzed c-Fos immunoreactivity in brain regions associated with emotional regulation after 30-day oral FLX treatment in male and female mice. Our findings showed a significant reduction in c-Fos expression in FLX-treated groups compared to controls, suggesting decreased cellular activity in several brain regions. Furthermore, significant sex differences were observed as male mice exhibited higher c-Fos activity than females. Treatment interaction indicated FLX might reduce these sex disparities, except in the CA2 region of the hippocampus, where males maintained higher activity. Notably, FLX appeared to minimize the sex-based disparities in c-Fos expression in several regions, suggesting that FLX equalizes cellular activity across sexes in areas associated with cognitive and emotional functions. Altogether, these data indicate that FLX modulates cellular activity via a sex-dependent mechanism, which highlights the relevance of considering sex differences in the assessment of the neurobiological effects of FLX.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149735"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-24DOI: 10.1016/j.brainres.2025.149734
Xiaojia Yang , Meng Jiang , Min Wu , Xin Jin , Xinyu Wang , Lan Lv , Liquan Liu
{"title":"Crocin drives intestinal microbiota variation in a rat model of Alzheimer’s disease by reducing DKK3 expression","authors":"Xiaojia Yang , Meng Jiang , Min Wu , Xin Jin , Xinyu Wang , Lan Lv , Liquan Liu","doi":"10.1016/j.brainres.2025.149734","DOIUrl":"10.1016/j.brainres.2025.149734","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is a common neurodegenerative disease. Targeting DKK3-mediated intestinal microbiota (IM) variation is a promising strategy to treat AD. Crocin can alter IM distribution and inhibit DKK3 expression. We aimed to explore whether Crocin alleviates AD by regulating DKK3-mediated IM variation.</div></div><div><h3>Methods</h3><div>AD animal models were established by injecting Aβ<sub>1-42</sub> into the brains of rats. Subsequently, AD rats were overexpressed with DKK3 and treated with Crocin. Morris water maze and passive avoidance tests were performed to assess the learning and memory abilities of the rats. The effect of Crocin on brain Aβ<sub>1-42</sub> and p-tau levels, serum proinflammatory cytokine (TNF-α, IL-1β and IL-6) levels were analyzed. Then, hippocampal pathological damage of the rats was evaluated. Furthermore, DKK3, NeuN, Bax, BCL-2 expressions and GSK-3β phosphorylation were measured by immunohistochemistry and Western blot. Moreover, rat feces were collected for 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>Crocin improved learning and memory abilities of AD rats. Additionally, Crocin inhibited brain Aβ<sub>1-42</sub> and p-tau levels, and serum proinflammatory cytokine levels for AD rats. It was also observed that Crocin attenuated hippocampal pathological damage, inhibited DKK3, Bax expressions and GSK-3β phosphorylation, but increased NeuN, BCL-2 expressions for AD rats. Notably, Crocin increased the α and β diversity of the IM in AD rats. However, DKK3 overexpression reversed these situations. Additionally, Crocin treatment led to an increase in <em>Prevotellaceae_NK3B31_group</em>, alongside reductions in <em>Lachnospiraceae UCG-001</em> and <em>Family_XIII_AD3011_group</em>.</div></div><div><h3>Conclusion</h3><div>Crocin alleviated AD by regulating DKK3-mediated IM variation, suggesting that DKK3-mediated IM variation was a potential therapeutic target for AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149734"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-22DOI: 10.1016/j.brainres.2025.149721
Lei Zhao , Menglan Yin , Meng Wang , Yushuang Cao , Lichen Guo , Lijuan Chai , Shaoxia Wang , Limin Hu , Qing Yuan
{"title":"Earthworm extract improves cerebral ischemia–reperfusion injury through regulating microglia polarization and promoting cerebral angiogenesis in vitro and in vivo","authors":"Lei Zhao , Menglan Yin , Meng Wang , Yushuang Cao , Lichen Guo , Lijuan Chai , Shaoxia Wang , Limin Hu , Qing Yuan","doi":"10.1016/j.brainres.2025.149721","DOIUrl":"10.1016/j.brainres.2025.149721","url":null,"abstract":"<div><div>Promoting the polarization of microglia towards an anti-inflammatory M2 phenotype probably be exploited as a potential strategy for stroke. While earthworm has been shown to possess anti-inflammatory effects, its potential impact on microglial polarization and post-stroke recovery remains unclear. In in vitro experiments, BV2 mouse microglial cells were stimulated with lipopolysaccharide (LPS). Then, BV2 cells were given Earthworm extract (EWE). The expression levels of microglial phenotypic markers (CD16 and CD206), as well as cytokines (including IL-1β, VEGF, IL-10, and TGFβ), were assessed using techniques such as RT-PCR, immunofluorescence, ELISA, or Western blot. Subsequently, the viability and angiogenic potential of HCMEC/D3 human endothelial cells treated with conditioned media obtained from BV2 cells exposed to EWE (EWE-CM) were evaluated using migration assay, and tube formation assay. In in vivo experiments, C57 black mouse (C57 BL/6 mice) underwent middle cerebral artery occlusion and reperfusion (MCAO/R) and received daily tail injections of EWE for a duration of three days. The pathological condition of the brain was assessed using neurological deficit scores, 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin (H&E), and Nissl staining. The expression levels of CD206+/IBA-1+, CD16+/IBA-1+, and ki67+/Biotinylated LEL in the brain were assessed using immunofluorescence staining. The results demonstrated that EWE significantly suppressed pro-inflammatory cytokines and stimulated anti-inflammatory cytokines in LPS-induced microglia in vitro. Moreover, the EWE-CM enhanced the viability and tube-forming capacity of HCMEC/D3 cells, thereby promoting angiogenesis through activation of the Ang1/Tie2/Ang2 pathway. Furthermore, administration of EWE not only significantly ameliorated neurological deficits and reduced infarct volumes but also suppressed the activation of microglial cells in MCAO/R-induced mice in vivo. Thereby, EWE can modulate microglial cell M1/M2 polarization and enhance angiogenesis which is possibly activating the Ang1/Tie2/Ang2 pathway after cerebral ischemia, offering a potential therapeutic strategy for stroke.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1861 ","pages":"Article 149721"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-22DOI: 10.1016/j.brainres.2025.149680
Qiong Zhou, Xiaoman Huang, Zihao Chen, Fuwei Wang, Lihua Xie, Qiang Sun, Jikun Du, Jiantao Lin, Baohong Li, Li Li
{"title":"Mechanism of Rhizoma Polygonati in the treatment of Alzheimer's disease based on network pharmacology and molecular docking.","authors":"Qiong Zhou, Xiaoman Huang, Zihao Chen, Fuwei Wang, Lihua Xie, Qiang Sun, Jikun Du, Jiantao Lin, Baohong Li, Li Li","doi":"10.1016/j.brainres.2025.149680","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149680","url":null,"abstract":"<p><strong>Objective: </strong>The therapeutic mechanisms of Rhizoma Polygonati (RP) on Alzheimer's disease (AD) were explored using network pharmacology methods and in vitro experiments for validation.</p><p><strong>Materials and methods: </strong>First, the main active ingredients and target proteins of RP were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and UniProt protein database. AD-related targets were predicted using the DisGeNET database. Subsequently, Protein-protein interaction (PPI) networks and core targets were analyzed using STRING. DAVID was utilized for GO annotation, while KEGG plug-in was employed to perform enrichment analysis of KEGG pathways. AutoDockTools were examined molecular docking. And the RP mechanism on AD was confirmed in vitro experimentation.</p><p><strong>Results: </strong>Screening identified 8 active ingredients, 76 potential targets, and 3397 CE-related genes, with 58 overlapping targets. 4 target proteins were analyzed through the PPI networks. The RP and AD shared 451 GO biological process items and 150 KEGG signal pathways. Molecular docking results showed that diosgenin (Dio) had strong binding abilities to AKT1 and Caspase 3. Dio inhibited apoptosis through AKT1/Caspase 3 pathway in the glutamate-induced SH-SY5Y cells in vitro.</p><p><strong>Conclusion: </strong>The study revealed RP's potential mechanisms in treating AD, offering a theoretical basis for clinical use, by integrating network pharmacology with in vitro experiments.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149680"},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-21DOI: 10.1016/j.brainres.2025.149720
Priscila Vázquez-León , Abraham Miranda-Páez
{"title":"Anxiolytic-like, anorexic, adipsogenic and anti-alcohol intake effects of acute taurine administration into dorsal periaqueductal gray of female and male adult Wistar rats","authors":"Priscila Vázquez-León , Abraham Miranda-Páez","doi":"10.1016/j.brainres.2025.149720","DOIUrl":"10.1016/j.brainres.2025.149720","url":null,"abstract":"<div><div>Taurine (TAU, 2-aminoethane sulphonic acid) is a semi-essential β sulfonated amino acid, one of the most abundant free amino acids in the body and the mammalian brain. Most studies on taurine have demonstrated its beneficial role at acute doses, administered either systemically or i.c.v., on numerous disease models and an inhibition of alcohol intake. The periaqueductal gray (PAG) is a key vertebrate midbrain structure for integrated defensive responses, including those representing stress and anxiety-like behavior. A strong relationship between anxiety and alcohol intake, besides the critical role of dorsal periaqueductal gray (D-PAG) in behavioral defensive and consummatory responses, has been shown. This study aimed to assess the pharmacological effects of taurine administration into D-PAG on anxiety-like behavior through the elevated plus maze test, as well as consummatory behavior through food, water, and alcohol intake and preference. Both female and male rats, either alcohol naïve or forced ethanol intake (since juvenile age with a chronic intermittent access model), were implanted with cannulae on the right side of D-PAG. We found that administering taurine into D-PAG elicits an anxiolytic-like effect and reduces food and water intake in all groups. Furthermore, taurine inhibits alcohol consumption by adult Wistar rats previously exposed to alcohol.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149720"},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-20DOI: 10.1016/j.brainres.2025.149715
Desmond Agboada, Roman Rethwilm, Wolfgang Seiberl, Wolfgang Mack
{"title":"The influence of pulse shape and current direction of TMS on test-retest reliability, and variability of measurement outcomes.","authors":"Desmond Agboada, Roman Rethwilm, Wolfgang Seiberl, Wolfgang Mack","doi":"10.1016/j.brainres.2025.149715","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149715","url":null,"abstract":"<p><strong>Background: </strong>Pulse parameters of transcranial magnetic stimulation (TMS) critically affect the stimulation outcomes. There is, however, a lack of understanding on how these parameters influence test-retest reliability and variability of single-pulse TMS protocols.</p><p><strong>Objectives: </strong>This study aims to investigate the effects of four combinations of pulse shapes and current directions (TMS-waveform conditions) on outcome measurements, test-retest reliability, and variability.</p><p><strong>Methods: </strong>Using robot-assisted neuronavigation, nineteen participants were stimulated with four TMS-waveform conditions in three repeated sessions within the same day. Sessions 1 and 2, and Sessions 1 and 3 were separated by 30 min, and approximately 7 h respectively. The four TMS-waveform conditions were: biphasic and monophasic pulses delivered in either posterior-anterior (PA) or anterior-posterior (AP) current directions. TMS protocols investigated were resting/active motor thresholds, stimulus intensity for inducing 1 mV peak-to-peak motor-evoked potential (MEP) amplitude, corticospinal excitability measurements (MEP amplitudes and latencies) with three inter-stimulus intervals (ISIs) of 5, 10, and 15 s; input-output (I/O) curve, and cortical silent period.</p><p><strong>Results: </strong>TMS-waveform influenced all spTMS protocol outcome measures except for the I/O. TMS pulses in the PA current direction induced less variable MEP amplitudes and latencies. Moderate to excellent test-retest reliability was also found for all protocols except the I/O, however TMS-waveform only influenced the reliability of the AMT and MEP latency protocols. Monophasic pulses in the PA direction were more reliable compared to pulses in AP for MEP latency while biphasic pulses in the AP direction showed significantly lower reliability compared to other TMS-waveform conditions for the AMT.</p><p><strong>Conclusion: </strong>This systematic evaluation does shed more light on protocols and TMS pulse parameters that induce reliable and less variable measurements.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149715"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-19DOI: 10.1016/j.brainres.2025.149717
Chirine Katrib , Camille Naidji , David Devos , Kelly Timmerman , Nicolas Durieux , Nathalie Dutheil , Erwan Bezard , Charlotte Laloux , Nacim Betrouni
{"title":"Texture features of T2w magnetic resonance imaging mirror tissue changes in Parkinson’s disease models","authors":"Chirine Katrib , Camille Naidji , David Devos , Kelly Timmerman , Nicolas Durieux , Nathalie Dutheil , Erwan Bezard , Charlotte Laloux , Nacim Betrouni","doi":"10.1016/j.brainres.2025.149717","DOIUrl":"10.1016/j.brainres.2025.149717","url":null,"abstract":"<div><div>After successful applications in the oncology field to provide new <em>in vivo</em> diagnosis and prognosis imaging features, texture analysis and more generally radiomics were also reported as having the potential to provide markers of different neurodegenerative processes. Indeed, in neurodegenerative diseases such as Parkinson’s disease (PD), there is a need for neuroprotective therapies, the development of which will be fundamentally aided by imaging biomarkers capable of inferring tissue changes such as loss of neurons in the nigro-striatal pathway or alpha synuclein aggregates that characterize PD. In this study, we therefore sought to decipher the relationship between signal changes measured using brain MRI texture features and histological changes in preclinical models of this disease.</div><div>Three rodent models were used: two toxin-based models, one involving 6-hydroxydopamine injection and the other using methyl-phenyl-tetrahydropyridine, and a third model based on alpha-synuclein overexpression. Animals had MR imaging with a <em>T2w</em> sequence evaluation and were sacrificed for histological analyses of the brains. Texture features were measured in different brain structures. The association analyses revealed significant correlations between the imaging features measured in the substantia nigra and the striatum with dopaminergic degeneration, as well as significant correlations between texture features in key structures (substantia nigra, striatum, thalamus, hippocampus and associative and cingulate cortices), and alpha-synuclein quantified in these regions.</div><div>These preliminary results suggest that MR signal changes captured using texture features reflect the underlying tissue changes occurring in the brain such as neuronal death and proteins accumulation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149717"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-17DOI: 10.1016/j.brainres.2025.149707
Xingli Tan , Xiaoli Su , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Shuyu Wang , Jing Wang , Honglin Feng
{"title":"COMM domain containing 4 inhibits hephaestin and ferroportin to enhance neuronal ferroptosis by disturbing the Cu-Fe balance in amyotrophic lateral sclerosis","authors":"Xingli Tan , Xiaoli Su , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Shuyu Wang , Jing Wang , Honglin Feng","doi":"10.1016/j.brainres.2025.149707","DOIUrl":"10.1016/j.brainres.2025.149707","url":null,"abstract":"<div><div>Dysregulation of copper and iron homeostasis contributes to the progression of amyotrophic lateral sclerosis (ALS), but the role and mechanism of COMM domain containing 4 (COMMD4) in ALS remains unclear. In this research, we showed that the expression of COMMD4 was upregulated in ALS cells and animal models. The increased COMMD4 induced neuronal ferroptosis by disrupting the Cu-Fe balance. Mechanistic studies indicated that COMMD4 inhibited ferroportin (FPN)-mediated neuronal iron efflux by inhibiting intracellular copper and hephaestin (HEPH). Our findings demonstrated that COMMD4 depletion exerts neuroprotective effects on ALS by increasing intracellular copper and activating HEPH/FPN pathway, rather than affecting the interaction between HEPH and FPN. Targeting COMMD4 and its downstream signaling pathways may offer potential therapeutic avenues for ALS.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1861 ","pages":"Article 149707"},"PeriodicalIF":2.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain ResearchPub Date : 2025-05-17DOI: 10.1016/j.brainres.2025.149703
Zahra Soleimani , Shima Davoudi , Fatemeh Saffarzadeh , Gila Behzadi , Mehdi Mehdizadeh , Mona Rahdar , Narges Hosseinmardi , Mahyar Janahmadi , Mohammad J. Eslamizade
{"title":"Restoring neuronal excitability and spatial memory through inhibiting amyloid-β-induced hyperactive NF-κB in a rat model of Alzheimer’s disease","authors":"Zahra Soleimani , Shima Davoudi , Fatemeh Saffarzadeh , Gila Behzadi , Mehdi Mehdizadeh , Mona Rahdar , Narges Hosseinmardi , Mahyar Janahmadi , Mohammad J. Eslamizade","doi":"10.1016/j.brainres.2025.149703","DOIUrl":"10.1016/j.brainres.2025.149703","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder associated with aberrant neuronal activity. In AD, NF-κB, a key transcription factor and inflammatory mediator, becomes hyperactive, influencing gene expression, and likely neuronal excitability. This study investigates whether inhibiting intracortical injection of amyloid-β peptides (Aβ)-induced hyperactive NF-κB can restore spatial memory impairment and abnormal neuronal activity in rats. We observed that intracortical injection of Aβ increases immunoreactivity of phosphorylated-p65 in CA1 pyramidal neurons. We demonstrated that <em>in vivo</em> treatment of rats with JSH-23 restores anxiety-like behaviors as well as spatial learning and memory, as assessed by elevated plus maze and Morris water maze, respectively. In addition, using patch-clamp recording we showed that the intrinsic excitability of CA1 pyramidal neurons, particularly in terms of the evoked spikes, is reduced in Aβ-injected rats along with altered resting membrane properties. Incubating acute brain slices from control rats in aCSF containing JSH-23 did not influence the neuronal activity. In contrast, this incubation restored almost all of the passive- and activity-dependent properties of CA1 pyramidal neurons in brain slices from Aβ-injected rats. Furthermore, we found that Aβ-induced enhancement of Ih currents and after-hyperpolarization amplitude (AHP) are reduced by JSH-23 incubation, possibly underlying rescuing effects of NF-κB inhibition at behavioral and cognitive level. Collectively, our results suggest that hyperactive NF-κB signaling in AD is associated with abnormal neuronal activity and deficits in cognitive functions. Moreover, pharmacologic inhibition of this signaling molecule restores neuronal excitability, as well as rescues spatial memory, likely through influencing Ih currents and AHP.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1861 ","pages":"Article 149703"},"PeriodicalIF":2.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bridging the gap between structural and metabolic neuroimaging via MRI-to-PET synthesis: A tri-attention enhanced GAN approach","authors":"Jinhua Sheng , Haodi Zhu , Rougang Zhou , Qiao Zhang , Jialei Wang , Ziyi Ying","doi":"10.1016/j.brainres.2025.149691","DOIUrl":"10.1016/j.brainres.2025.149691","url":null,"abstract":"<div><div>Magnetic resonance imaging (MRI) and positron emission tomography (PET) are two essential neuroimaging modalities that provide complementary structural and metabolic information about the brain, thereby enhancing diagnostic precision for brain disorders such as Alzheimer’s disease (AD). To address the limitations of missing modality data, we propose a novel 3D GAN-based framework for MRI-to-PET neuroimage synthesis, incorporating a Tri-Attention module to integrate spatial, channel, and frequency attention across multiple scales. The proposed method enables the generation of complementary metabolism information by synthesizing PET scans, effectively bridging the modality gap. The effectiveness of the proposed method is evaluated on a subset of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Experimental results demonstrate the superiority of our approach, achieving significant improvements in image quality metrics (SSIM: 0.882, PSNR: 26.508) and clinical metrics (SUVR), outperforming state-of-the-art methods. These findings underscore the potential of our framework to bridge the gap between structural and metabolic information, offering a promising tool for cross-modality neuroimage synthesis and clinical applications.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1862 ","pages":"Article 149691"},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}