Brain Research Bulletin最新文献

{"title":"Machine learning approach effectively discriminates between Parkinson’s disease and progressive supranuclear palsy: Multi-level indices of rs-fMRI","authors":"Weiling Cheng ,&nbsp;Xiao Liang ,&nbsp;Wei Zeng ,&nbsp;Jiali Guo ,&nbsp;Zhibiao Yin ,&nbsp;Jiankun Dai ,&nbsp;Daojun Hong ,&nbsp;Fuqing Zhou ,&nbsp;Fangjun Li ,&nbsp;Xin Fang","doi":"10.1016/j.brainresbull.2025.111476","DOIUrl":"10.1016/j.brainresbull.2025.111476","url":null,"abstract":"<div><h3>Aim</h3><div>Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) present similar clinical symptoms, but their treatment options and clinical prognosis differ significantly. Therefore, we aimed to discriminate between PD and PSP based on multi-level indices of resting-state functional magnetic resonance imaging (rs-fMRI) via the machine learning approach.</div></div><div><h3>Materials and methods</h3><div>A total of 58 PD and 52 PSP patients were prospectively enrolled in this study. Participants were randomly allocated to a training set and a validation set in a 7:3 ratio. Various rs-fMRI indices were extracted, followed by a comprehensive feature screening for each index. We constructed fifteen distinct combinations of indices and selected four machine learning algorithms for model development. Subsequently, different validation templates were employed to assess the classification results and investigate the relationship between the most significant features and clinical assessment scales.</div></div><div><h3>Results</h3><div>The classification performance of logistic regression (LR) and support vector machine (SVM) models, based on multiple index combinations, was significantly superior to that of other machine learning models and combinations when utilizing automatic anatomical labeling (AAL) templates. This has been verified across different templates.</div></div><div><h3>Conclusions</h3><div>The utilization of multiple rs-fMRI indices significantly enhances the performance of machine learning models and can effectively achieve the automatic identification of PD and PSP at the individual level.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111476"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686766","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":"Whole brain gray matter volume may mediate the relationship between light physical activity and Body Mass Index in middle-aged Japanese adults.","authors":"Juan Cesar D Pineda, Keisuke Kokubun, Yoshinori Yamakawa","doi":"10.1016/j.brainresbull.2025.111471","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111471","url":null,"abstract":"<p><p>Obesity is a multifactorial condition that cannot be fully explained by traditional energy-balance models. Recent studies highlight the role of brain structure-particularly gray matter volume-as a potential risk factor of obesity. Physical activity (PA) has been shown to enhance gray matter volume, particularly in older adults. While prior studies have linked physical activity (PA) with both brain structure and Body Mass Index (BMI), few have examined whether brain structure may account for the association between PA and obesity. Therefore, this study explored the potential mediating role of brain structure in the association between PA and BMI in a cross-sectional sample of Japanese adults. PA was assessed using the Japanese version of the International Physical Activity Questionnaire - Short Form (IPAQ-SF). PA was assessed across three intensity levels (Intense, Moderate, and Light), in terms of duration (minutes per week) and frequency (number of days per week). Brain structure was measured as total gray matter volume, using the Gray Matter Brain Healthcare Quotient (GM-BHQ). Multiple hierarchical linear regression revealed only light PA had individual associations with increased GM-BHQ (R = 0.803, b = 0.188, p = 0.002) and decreased BMI (R = 0.303, b = -0.165, p = -0.096). GM-BHQ also showed a stronger association with BMI than PA alone (R = 0.367, b = -0.313, p = 0.030). Path analysis revealed a potential mediating role of brain structure in the link between PA and BMI (indirect effect = 0.052, p = 0.030). These findings offer new insights into the neurobiological mechanisms underlying obesity and highlight the potential of brain health as a key factor in weight regulation strategies.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111471"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682064","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":"Gut microbiota dysbiosis and disturbed tryptophan metabolism mediate cognitive impairment in mice with circadian rhythm disruption","authors":"Haiyue Song ,&nbsp;Huiliang Zhang ,&nbsp;Xuan Qin ,&nbsp;Yi Liu ,&nbsp;Yiwen Lai ,&nbsp;Wenqi Yang ,&nbsp;Lun Zhang ,&nbsp;Wenting Hu ,&nbsp;Xiaochuan Wang ,&nbsp;Ji Zeng ,&nbsp;Rong Liu","doi":"10.1016/j.brainresbull.2025.111473","DOIUrl":"10.1016/j.brainresbull.2025.111473","url":null,"abstract":"<div><div>Circadian rhythm disorder (CRD) is a risk factor for cognitive deficits, yet its mechanisms remain unclear. We previously found CRD model mice developed cognitive impairment mediated through gut microbiota disturbance, intestinal barrier damage, and microglia activation, but the signaling pathway was undefined. Here, we show CRD induces cognitive deficits and gut microbiota disturbance in mice. Fecal microbiota transplantation (FMT) from CRD mice to normal mice reproduced intestinal barrier damage, microglia activation, neuronal damage, and cognitive deficits. Notably, gut metabolite analysis revealed significant alterations, with tryptophan metabolism being particularly affected: tryptophan decreased by 26.9 % and 5-hydroxytryptophan (5-HTP) by 30.7 % (both <em>P</em> &lt; 0.05). Dietary tryptophan supplementation restored serum tryptophan and 5-HTP levels, ameliorating the neuronal damage and cognitive deficits caused by CRD gut microbiota. Collectively, these findings indicate that disturbances in gut microbiota and metabolites play a key role in CRD-induced neurological damage in mice, suggesting targeting the gut microbiota or tryptophan metabolism may prevent CRD-induced cognitive dysfunction.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111473"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Autologous Fecal Microbiota Transplantation on Fear Memory and Anxiety Abnormalities Induced by Single Prolonged Stress -Implication of gut-brain axis regulation.","authors":"Yu-Yen Cheng, Chen-Cheng Lin, Che-Se Tung, Cheng-Che Liu, Yia-Ping Liu","doi":"10.1016/j.brainresbull.2025.111472","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111472","url":null,"abstract":"<p><p>Increasing evidence suggests that alterations in the gut microbiota play a crucial role in the pathophysiology of psychiatric disorders, including post-traumatic stress disorder (PTSD). This implies that restoring gut microbiota might serve as a therapeutic strategy, with autologous fecal microbiota transplantation (FMT) being the most promising treatment due to its effectiveness and fewer pharmacological side effects. However, the hypothesis that adjusting gut microbiota may help to restore the impairment of fear memory is still less examined. To evaluate this hypothesis, we employed single prolonged stress (SPS) rat model to examine the impact of autologous FMT on PTSD-related fear memory extinction retention deficits and increased anxiety, and to investigate changes in the levels of gut microbiota, central monoamines, and plasma corticosterone. The correlations between gut microbiota and central serotonin (5-HT) with fear extinction retention deficits and anxiety were analyzed. Note that littermates were used in the gut microbiota analysis to minimize individual differences. Our results demonstrated that autologous FMT significantly ameliorated SPS-induced deficits in fear extinction retention and conditioned anxiety but did not mitigate unconditioned anxiety. These improvements were significantly correlated with the restoration of 5-HT levels in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and hypothalamus (HT). Autologous FMT also reversed SPS-induced reductions in plasma corticosterone level. Additionally, fecal microbiota analysis revealed significant changes at the genus level, with the relative abundance of the Prevotellaceae Ga6A1 group reduced after SPS, and Intestinimonas increased by FMT, as well as some taxa significantly correlated with fear extinction retention deficits. This study suggests that autologous FMT offers potential as a novel therapeutic strategy for PTSD.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111472"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and mechanisms of macrophages in chronic pain: A peripheral-to-central perspective","authors":"Jiao Liu ,&nbsp;Yeru Chen ,&nbsp;Gang Chen","doi":"10.1016/j.brainresbull.2025.111470","DOIUrl":"10.1016/j.brainresbull.2025.111470","url":null,"abstract":"<div><div>Chronic pain is a worldwide health concern that profoundly impacts patients' quality of life and imposes a substantial economic burden on society. The development is influenced by intricate physiological mechanisms, notably the sensitization of peripheral nociceptors and central sensitization. Macrophages, essential immune cells, are pivotal in the onset and maintenance of chronic pain. This article analyzes the functions of macrophages in peripheral nociceptors, dorsal root ganglia (DRG), and the central nervous system (CNS), particularly in the spinal dorsal horn and brain. Research indicates that peripheral macrophages elevate nociceptor sensitivity via the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and PGE₂; in the DRG, macrophages amplify pain signaling by influencing neuronal excitability; within the (CNS), microglia and border-associated macrophages (BAM) perform unique functions in neuroinflammation and pain perception. Microglia enhance pain perception by facilitating central sensitization, whereas BAMs, located at the borders of the central nervous system, participate in neurovascular connections, immune control, and associated mechanisms. Despite considerable advancements, the precise functional roles of macrophages across many anatomical locations remain inadequately investigated and lack systematic comparison. Future study ought to concentrate on the geographically different processes of macrophages, specifically employing single-cell transcriptomics and other modern technologies to elucidate macrophage heterogeneity and its intricate role in chronic pain. An enhanced comprehension of these pathways may facilitate novel approaches for macrophage-targeted treatments in chronic pain management.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111470"},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667127","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":"Quantitative study of changes in the hippocampus after whole-brain radiotherapy via multisequence magnetic resonance imaging radiomics","authors":"Rui Liu ,&nbsp;Guan-Zhong Gong ,&nbsp;Shan-Shan Du ,&nbsp;Kang-Ning Meng ,&nbsp;Ruo-Zheng Wang ,&nbsp;Yong Yin","doi":"10.1016/j.brainresbull.2025.111461","DOIUrl":"10.1016/j.brainresbull.2025.111461","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Multisequence magnetic resonance imaging (MRI) radiomic features were used to analyze dynamic changes in the hippocampus after whole-brain radiotherapy (WBRT), thus providing an objective basis for the early prediction of hippocampal radiation injury.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Seventy-five patients with brain metastases (BMs) who received WBRT underwent MRI scanning (including T1-weighted imaging [T1WI], contrast-enhanced [CE]-T1WI, T2-weighted imaging [T2WI], T2-weighted Fluid-Attenuated Inversion Recovery imaging [T2 FLAIR] and diffusion weighted imaging [DWI]) before WBRT (MRI&lt;sub&gt;pre&lt;/sub&gt;), after WBRT (MRI&lt;sub&gt;post&lt;/sub&gt;, 26.22 ± 13.05 days after the MRI&lt;sub&gt;pre&lt;/sub&gt; scan), and at follow-up WBRT (MRI&lt;sub&gt;follow&lt;/sub&gt;, 393.45 ± 210.33 days after the MRI&lt;sub&gt;post&lt;/sub&gt; scan). Radiomics features were subsequently extracted from delineations of the hippocampus on the different sequences. Changes in the hippocampal volume and radiomics features of the sequences were analyzed in the MRI&lt;sub&gt;post&lt;/sub&gt; and MRI&lt;sub&gt;follow&lt;/sub&gt; sequences relative to the MRI&lt;sub&gt;pre&lt;/sub&gt; sequences. The features were then organized as follows: (1) Group&lt;sub&gt;1&lt;/sub&gt; features included those features that were significantly different among MRI&lt;sub&gt;pre&lt;/sub&gt;, MRI&lt;sub&gt;post&lt;/sub&gt;, and MRI&lt;sub&gt;follow&lt;/sub&gt; scans; and (2) Group&lt;sub&gt;2&lt;/sub&gt; features included those features that were significantly different between MRI&lt;sub&gt;pre&lt;/sub&gt; and MRI&lt;sub&gt;follow&lt;/sub&gt; scans and between MRI&lt;sub&gt;post&lt;/sub&gt; and MRI&lt;sub&gt;follow&lt;/sub&gt; scans.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;(1) The average MRI&lt;sub&gt;post&lt;/sub&gt; and MRI&lt;sub&gt;follow&lt;/sub&gt; hippocampal volumes were 3.32 ± 0.49 cm&lt;sup&gt;3&lt;/sup&gt; and 2.95±0.45 cm&lt;sup&gt;3&lt;/sup&gt;, respectively, which were 1.68 % and 12.51% lower than the MRI&lt;sub&gt;pre&lt;/sub&gt; volume (3.41 ± 0.49 cm&lt;sup&gt;3&lt;/sup&gt;), respectively (p &lt; 0.05). (2) Radiomics analysis revealed that 88 features were significantly different (p &lt; 0.05) across the MRI&lt;sub&gt;pre&lt;/sub&gt;, MRI&lt;sub&gt;post&lt;/sub&gt;, and MRI&lt;sub&gt;follow&lt;/sub&gt; scans. The T2WI sequence contained the greatest number of significant features (n = 42). Among Group&lt;sub&gt;1&lt;/sub&gt; features (n = 57), enrichment was observed in T2WI (n = 34) and T1WI (n = 22). The feature exhibiting the highest rate of change was GLCM-ClusterShade (range: 83.87–281.62 %). All 12 significant change features in CE-T1WI were observed in Group&lt;sub&gt;2&lt;/sub&gt;. Although the overall timing difference for T2 FLAIR was not significant (p = 0.064), DWI contained a single Group&lt;sub&gt;2&lt;/sub&gt; feature (p = 0.032). Within Group&lt;sub&gt;2&lt;/sub&gt;, GLCM-ClusterTendency exhibited the largest rate of change (range: 37.16–51.27 %).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Compared with volume, multisequence MRI radiomics features more directly reflect dynamic microscopic hippocampal changes across MRI&lt;sub&gt;pre&lt;/sub&gt;, MRI&lt;sub&gt;post&lt;/sub&gt;, and MRI&lt;sub&gt;follow&lt;/sub&gt; time points. T2WI and T1WI captured early sustained radiomics alterations, whereas CE-T1WI refle","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111461"},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658409","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 approach to arousal disorder classification using deformable convolution and adaptive multiscale features in EEG signals.","authors":"Andia Foroughi, Fardad Farokhi, Fereidoun Nowshiravan Rahatabad, Alireza Kashaninia","doi":"10.1016/j.brainresbull.2025.111468","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111468","url":null,"abstract":"<p><p>Diagnosing sleep phases, arousal problems, and apnea episodes using Polysomnography (PSG) signals is often time-consuming. However, automated approaches have demonstrated promising results. Early detection of sleep disturbances can facilitate the diagnosis of neuropathologies before they progress. Given the significance of sleep events in diagnosing and treating sleep disorders, automated arousal disorder classification is increasingly crucial. Timely intervention for arousal disorders, if detected early, can potentially slow the progression of neuropathological illnesses such as Multiple System Atrophy (MSA), Parkinson's, and Alzheimer's disease. While PSG signals are sometimes necessary for clinical diagnoses, Electroencephalography (EEG) is often underutilized due to its labor-intensive nature. Automated methods for detecting, analyzing, and classifying arousal disorders offer significant benefits. In this research, we propose a novel method to classify arousal disorders from EEG data and extract post-classification diagnostic features. To our knowledge, this is the first instance of such categorization achieved using a deformable convergence network. Our proposed model, a hierarchical multiscale deformable attention module, excels at detecting complex and abnormal patterns in EEG data. We apply this model after segmenting EEG data into 30-second windows and generating spectrogram images. This study aims to evaluate our model's effectiveness in handling imbalanced classification and reducing false positive rates in arousal detection. We analyzed data from 994 participants in the 2018 PhysioNet Challenge study who experienced sleep-related micro- and macro-arousal events. Our method achieved an accuracy rate exceeding 96%, outperforming other multi-scale channel attention modules. This approach enables future studies to objectively, efficiently, and precisely examine various arousal disorders. Additionally, we investigated the effect of multimodal signal fusion and observed that integrating EEG with ECG significantly enhances classification performance, highlighting the value of combining cortical and autonomic information in arousal disorder detection.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111468"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658407","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":"Resting-state functional magnetic resonance imaging and tryptophan hydroxylase-2 methylation interaction in major depressive disorder","authors":"Zhi Xu ,&nbsp;Tingting Tan ,&nbsp;Yan Jiang ,&nbsp;Haiping Tang ,&nbsp;Bingwei Chen ,&nbsp;Wenji Chen ,&nbsp;Yonggui Yuan","doi":"10.1016/j.brainresbull.2025.111469","DOIUrl":"10.1016/j.brainresbull.2025.111469","url":null,"abstract":"<div><h3>Background</h3><div>Functional abnormalities in different brain regions are related to major depressive disorder (MDD). In our previous study, we demonstrated that DNA methylation of Tryptophan Hydroxylase-2 (TPH2) is related to the occurrence of MDD. The present study aimed to identify the interaction of the functional activities of brain regions identified as regions of interest (RoI) in MDD with TPH2 gene methylation to explore their relationship.</div></div><div><h3>Methods</h3><div>Data from 98 patients with MDD and 63 controls were utilized. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and fractional ALFF (fALFF), were used to identify ROIs regions in the RESTPlus Software of MATLAB. General linear regression (GLM) was performed to analyze the association between functional connectivity (FC) found in rs-fMRI and the effect of TPH2 DNA methylation in patients with MDD and controls.</div></div><div><h3>Results</h3><div>In the rs-fMRI analysis, the ALFF of right superior generalized gyrus (STG) was significantly different between the MDD and HCs groups (p &lt; 0.05). The ReHo of right Middle temporal gyrus (MTG) and left middle occipital gyrus (MOG) were significantly different between the two groups (p &lt; 0.05). These ROIs were used to further analyze the FC differences between MDD and HCs, and it was found that the FC of right STG and right superior frontal gyrus (SFG) and the FC of right MTG and right MOG were significantly different between the two groups (p &lt; 0.05). It was further found that the interaction between ALFF activity of the right STG and TPH2–5–203 methylation (β=-2.108, p = 0.004), ReHo activity level of the right MTG, and TPH2–5–203 methylation were correlated with the occurrence of MDD (β=-1.720, p = 0.018).</div></div><div><h3>Conclusion</h3><div>This study found that the functional activities of the temporal lobe, middle occipital gyrus, and superior frontal gyrus were abnormal in patients with MDD compared to HCs. Furthermore, the interaction of functional activities of the right superior temporal gyrus /middle temporal gyrus and TPH2 methylation were associated with the occurrence of MDD, suggesting that the combination of functional activities and DNA methylation was helpful for diagnosis of MDD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111469"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658410","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":"KAT5 knockdown alleviates microglial inflammatory injury following acute cerebral ischemia through enhanced STAT6 activity","authors":"Yixin Li ,&nbsp;Li Peng ,&nbsp;Yang Zhou ,&nbsp;Yan You ,&nbsp;Jin Jiang ,&nbsp;Yong Luo","doi":"10.1016/j.brainresbull.2025.111467","DOIUrl":"10.1016/j.brainresbull.2025.111467","url":null,"abstract":"<div><div>In ischemic stroke (IS), microglia exhibit dynamic functional shifts, contributing to tissue damage during the acute phase and promoting repair in the chronic phase. The mechanisms underlying these transitions are poorly understood. We utilized a KAT5 knockdown rat model in conjunction with a BV2 cell model to investigate the negative regulatory mechanism of Lysine Acetyltransferase 5 (KAT5) on Signal Transducer and Activator of Transcription 6 (STAT6) and its effects in IS. We determined that STAT6 activation occurred following an increase in STAT6 protein levels and its acetylation, suggesting negative regulation of STAT6 during the early stages of IS. Given that acetylation inhibits STAT6 activity, KAT5 was identified as a potential acetyltransferase for STAT6 through an online acetyltransferase prediction tool combined with mass spectrometry analysis. We observed increased KAT5 protein levels and KAT5-positive microglia/macrophages at 12 h post-ischemic injury. Co-immunoprecipitation confirmed the interaction between STAT6 and KAT5. KAT5 knockdown in microglia <em>in vitro</em> significantly reduced the production of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and increased anti-inflammatory cytokines IL-10 and transforming growth factor-β (TGF-β) levels by decreasing STAT6 acetylation and enhancing its transcriptional activity. KAT5 knockdown <em>in vivo</em> improved modified neurological severity scores (mNSS), food intake, and reduced infarct volumes, pathological damage, and microglial-mediated pro-inflammatory responses. These findings indicated that KAT5 is integral to the early suppression of STAT6 activity in microglia following cerebral ischemia. Therefore, targeting KAT5 to restore STAT6 activity represents a potential therapeutic approach to mitigate microglial inflammatory injury in the acute phase of IS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111467"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658408","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":"Alterations in whole-brain white matter fiber networks in individuals with autism spectrum disorder after social skills training","authors":"Gang-Qiang Han ,&nbsp;Siu-Ching Kat ,&nbsp;Hui Wang ,&nbsp;Yu-Lu Yang ,&nbsp;Zeng-Hui Ma ,&nbsp;Ting-Ni Yin ,&nbsp;Ya-Jing Sun ,&nbsp;Xin-Zhou Tang ,&nbsp;Xiao-Yun Gong ,&nbsp;Duo Wang ,&nbsp;Lei Li ,&nbsp;Bing-Xi Sun ,&nbsp;Li-Yang Zhao ,&nbsp;Xing Su ,&nbsp;Jia-Lu Chen ,&nbsp;Xiao Chen ,&nbsp;Han-Lin Wang ,&nbsp;Xue-Ying Li ,&nbsp;Hai-Long Liu ,&nbsp;Xue Li ,&nbsp;Jing Liu","doi":"10.1016/j.brainresbull.2025.111466","DOIUrl":"10.1016/j.brainresbull.2025.111466","url":null,"abstract":"<div><div>Social skills training (SST) has demonstrated efficacy in improving social deficits in individuals with autism spectrum disorder (ASD), but the underlying neural mechanisms remain unclear. This study investigated alterations in whole-brain white matter network topology after SST in ASD individuals and explored potential correlation with improvements in social interaction deficits. 38 ASD patients aged 12 - 30 years were recruited, including 19 who completed magnetic resonance imaging (MRI) scans and social responsiveness scale (SRS) assessments at both baseline and the endpoint of a 14-week SST (training group) and 19 age-, sex-, and IQ-matched patients who underwent MRI scans and SRS assessment at the same time points but did not receive SST (control group). White matter connectivity matrices were constructed using diffusion tensor imaging (DTI), and graph theory analysis was used to assess global and nodal network properties. Paired t-tests and independent-samples t-tests were used for within- and between-group comparisons, respectively. Pearson's partial correlation was used to examine associations between network changes and SRS scores changes. After SST, four edges showed significant changes in white matter connectivity (FDR-corrected), with three increased and one decreased in the training group. Changes in nodal betweenness were also observed. While SRS scores significantly decreased in the training group, no significant correlations were found between neuroimaging changes and behavioral improvements, possibly due to the limited sample size. These findings suggest that SST may reshape white matter network, offering insights into its neural mechanisms and informing novel ASD intervention strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111466"},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648643","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}