CNS Neuroscience & Therapeutics最新文献

{"title":"Biological Effects of Dietary Restriction on Alzheimer's Disease: Experimental and Clinical Investigations","authors":"Zijiao Liu,&nbsp;Jun Zhang,&nbsp;Fei Jiang,&nbsp;Cong Liu,&nbsp;Yaping Shao,&nbsp;Weidong Le","doi":"10.1111/cns.70392","DOIUrl":"https://doi.org/10.1111/cns.70392","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>Dementia can impose a heavy economic burden on both society and families. Alzheimer's disease (AD), the most prevalent form of dementia, is a complex neurodegenerative disease characterized by the abnormal deposition of extracellular amyloid β-protein (Aβ) and the aggregation of intracellular Tau protein to form neurofibrillary tangles (NFTs). Given the limited efficacy of pharmacological treatment, scientists have already paid more attention to non-pharmacological strategies, including dietary restriction (DR). DR refers to a nutritional paradigm aimed at promoting overall health by modifying the balance between energy consumption and expenditure. Studies have demonstrated that DR effectively extends the healthy lifespan, delays the aging process, and achieves promising results in the prevention and treatment of AD in preclinical studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this review we collected related studies and viewpoints by searching on PubMed database using the keywords. Most of the citations were published between 2015 and 2025. A few older literatures were also included due to their relevance and significance in this field.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first provide a concise overview of the current therapeutic and preventive strategies for AD. Then, we introduce several specific DR protocols and their favorable effects on AD. Furthermore, the potential mechanisms underlying the benefits of DR on AD are discussed. Finally, we briefly highlight the role of DR in maintaining brain health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review may offer valuable insights into the development of innovative non-pharmacological strategies for AD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal Internal Event-Driven Analysis of Dynamical Electroencephalographic Biomarkers in Depression During Emotional Auditory Task","authors":"Qinglin Zhao,&nbsp;Kunbo Cui,&nbsp;Hua Jiang,&nbsp;Zhongqing Wu,&nbsp;Lixin Zhang,&nbsp;Mingqi Zhao,&nbsp;Bin Hu","doi":"10.1111/cns.70382","DOIUrl":"https://doi.org/10.1111/cns.70382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study for the first time proposed a novel prefrontal internal event-driven analytic framework for electroencepalography (EEG) data, which aim to dynamically resolve neural processes during natural emotional auditory tasks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The framework employed a novel unsupervised time-series clustering model for internal prefrontal event extraction, which supports event-related analyses with the absence of external event labeling. The framework was validated using a 64-channel EEG data obtained from 110 (55 depressed) subjects in a three-polar (positive, neutral, and negative) emotional-auditory task.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results suggest that anhedonia in depressed patients are associated with high activation levels in multiple brain regions during specific internal events, and we found that cross-frequency modulation of the bilateral prefrontal lobe with other relevant regions revealed completely different unidirectional patterns for the positive and negative tasks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study confirmed the effectiveness of the framework in resolving fine-grained internal event-driven neural processes without relying on traditional precise event-related data acquisision paradigms that often require high attention on the task events and causes high cognitive load. Our study present new insights for identifying dynamical electroencephalographic biomarkers in depression, which potentially provide EEG signal decoding solutions for EEG feedback-based closed-loop intervention of depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal Models of Traumatic Brain Injury and Their Relevance in Clinical Settings","authors":"Payal Chauhan,&nbsp;Nikita Yadav,&nbsp;Karan Wadhwa,&nbsp;Subbulakshmi Ganesan,&nbsp;Chakshu Walia,&nbsp;Gulshan Rathore,&nbsp;Govind Singh,&nbsp;Mosleh Mohammad Abomughaid,&nbsp;Abhilasha Ahlawat,&nbsp;Athanasios Alexiou,&nbsp;Marios Papadakis,&nbsp;Niraj Kumar Jha","doi":"10.1111/cns.70362","DOIUrl":"https://doi.org/10.1111/cns.70362","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) is a significant concern that often goes overlooked, resulting from various factors such as traffic accidents, violence, military services, and medical conditions. It is a major health issue affecting people of all age groups across the world, causing significant morbidity and mortality. TBI is a highly intricate disease process that causes both structural damage and functional deficits. These effects result from a combination of primary and secondary injury mechanisms. It is responsible for causing a range of negative effects, such as impairments in cognitive function, changes in social and behavioural patterns, difficulties with motor skills, feelings of anxiety, and symptoms of depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TBI associated various animal models were reviewed in databases including PubMed, Web of Science, and Google scholar etc. The current study provides a comprehensive overview of commonly utilized animal models for TBI and examines their potential usefulness in a clinical context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite the notable advancements in TBI outcomes over the past two decades, there remain challenges in evaluating, treating, and addressing the long-term effects and prevention of this condition. Utilizing experimental animal models is crucial for gaining insight into the development and progression of TBI, as it allows us to examine the biochemical impacts of TBI on brain mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This exploration can assist scientists in unraveling the intricate mechanisms involved in TBI and ultimately contribute to the advancement of successful treatments and interventions aimed at enhancing outcomes for TBI patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA ENSSSCG00000035331 Alleviates Hippocampal Neuronal Ferroptosis and Brain Injury Following Porcine Cardiopulmonary Resuscitation by Regulating the miR-let7a/GPX4 Axis","authors":"Mao Zhang,&nbsp;Wenbin Zhang,&nbsp;Ziwei Chen,&nbsp;Lu He,&nbsp;Qijiang Chen,&nbsp;Pin Lan,&nbsp;Lulu Li,&nbsp;Xianlong Wu,&nbsp;Xingui Wu,&nbsp;Jiefeng Xu","doi":"10.1111/cns.70377","DOIUrl":"https://doi.org/10.1111/cns.70377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following successful cardiopulmonary resuscitation, those survivors of cardiac arrest (CA) often suffer from severe brain injury, and the latter can result in significant mortality and morbidity. Emerging evidence implicates that ferroptosis is involved in the pathogenesis of post-resuscitation brain injury, and its regulatory mechanisms remain to be investigated. Recently, some studies manifested that long noncoding RNAs could be critical regulators of cell ferroptosis in diverse ischemia–reperfusion injuries of vital organs. This study was designed to explore the role and mechanism of a newly screened long noncoding RNA ENSSSCG00000035331 in alleviating post-resuscitation hippocampal neuronal ferroptosis and further investigate its potential regulation by a novel antioxidant sulforaphane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Healthy male pigs and mice were used to establish the models of CA and resuscitation in vivo. A hypoxia/reoxygenation (H/R) model using primary porcine hippocampal neurons was constructed to replicate post-resuscitation brain injury in vitro. We found that the expression of ENSSSCG00000035331 was significantly decreased in the post-resuscitation impaired hippocampus using RNA sequencing analysis and verification. Subsequently, ENSSSCG00000035331 overexpression significantly reduced ferroptosis-related ferrous iron and reactive oxygen species production while markedly increased glutathione and further alleviated post-resuscitation brain injury. Mechanistically, ENSSSCG00000035331 interacted with miR-let7a, then inhibited its binding with glutathione peroxidase 4 (GPX4) mRNA and finally promoted the recovery of the latter's translation after H/R stimulation. In addition, sulforaphane treatment significantly increased ENSSSCG00000035331 and GPX4 expression while markedly decreased miR-let7a expression and hippocampal neuronal ferroptosis and finally alleviated post-resuscitation brain injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlighted that ENSSSCG00000035331 was a critical regulator of hippocampal neuronal ferroptosis after CA and resuscitation by targeting the miR-let7a/GPX4 axis, and additionally, sulforaphane might be a promising therapeutic agent for alleviating post-resuscitation brain injury by regulating the signaling axis mentioned above.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models","authors":"Xingzhi Wang,&nbsp;Wenqi Mao,&nbsp;Li Du,&nbsp;Fei Wang,&nbsp;Ye Pang,&nbsp;Yangdanyu Li,&nbsp;Guangci Xu,&nbsp;Guiyun Cui","doi":"10.1111/cns.70395","DOIUrl":"https://doi.org/10.1111/cns.70395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Microglial activation plays a crucial role in neuroinflammation following ischemic stroke. This study was conducted to investigate the role and potential mechanisms of MK5 within microglial cells in the inflammatory response following ischemic stroke in mice in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microglia-specific conditional MK5 knockout (MK5 cKO) mice and their control mice (MK5^f/f) were subjected to middle cerebral artery occlusion (MCAO). BV2 cells (a mouse microglial cell line) were transfected with small interfering RNA (siRNA) to knock down MK5 levels and subsequently exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to simulate ischemic conditions in vitro. Following MCAO, behavioral tests and infarct volume measurements were conducted. Levels of cytokines and microglial markers were evaluated using qPCR and Western blotting, while immunofluorescence was employed to observe microglial activation. Additionally, Western blotting was performed to assess the phosphorylation of HSP27 and NF-κB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the control group, the knockout of the MK5 gene in microglia significantly exacerbated neurological deficits and increased infarct volume in MCAO mice. The loss of the MK5 promoted inflammation by upregulating pro-inflammatory factors and downregulating anti-inflammatory factors, while also enhancing microglial activation in both MCAO mice and BV2 microglial cells subjected to OGD/R. Furthermore, the knockout of the MK5 gene in microglia reduced the phosphorylation levels of HSP27 and increased the phosphorylation levels of NF-κB in the aforementioned models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microglial MK5 plays a critical role in the ischemic neuroinflammatory response by regulating the phosphorylation of HSP27 and NF-κB, positioning it as a potential target for stroke treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction and SHAP Analysis Integrating Morphological and Hemodynamic Parameters for Unruptured Intracranial Aneurysm Occlusion After Flow Diverter Treatment","authors":"Hongchen Zhang,&nbsp;Chuanhao Lu,&nbsp;Zhen Hu,&nbsp;Deyu Sun,&nbsp;Liang Li,&nbsp;Hongxing Wu,&nbsp;Hua Lu,&nbsp;Bin Lv,&nbsp;Jun Wang,&nbsp;Shuhui Dai,&nbsp;Xia Li","doi":"10.1111/cns.70386","DOIUrl":"https://doi.org/10.1111/cns.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although most unruptured intracranial aneurysms (UIAs) have good prognosis after flow diverter (FD) treatment, some remain unoccluded for extended periods, posing a persistent rupture risk. This study aims to develop a predictive model for UIA occlusion after FD treatment through integrating morphological and hemodynamic parameters, which may be critical for personalized postoperative management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from patients with single UIAs treated with stand-alone FD were collected from June 2018 to December 2022 in four cerebrovascular disease centers. Morphological parameters were obtained from 3D reconstructed aneurysm models, and hemodynamic parameters were derived by computational fluid dynamics (CFD) analysis. A predictive model for aneurysm occlusion was constructed using various machine learning algorithms, including logistic regression, Random Forest, XGBoost, and K-Nearest Neighbors. Model performances were evaluated through repeated cross-validation, 0.632 bootstrap, and 0.632+ bootstrap. Shapley additive explanation (SHAP) analysis was employed to assess the contribution of each parameter to UIA occlusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-nine patients were reviewed; a total of 51 cases met the criteria, with an average age of 53.9 ± 9.9 years. The average aneurysm diameter was 3.72 ± 2.72 mm, comprising 29 occlusions and 22 non-occlusions. Five variables were selected for further modeling, including follow-up time &gt; 6 months, aneurysm rupture ratio (ArR), occlusion ratio (OsR), parent artery wall shear stress (WSS), and the change of parent artery WSS. Logistic regression outperformed other algorithms, achieving an area under the curve (AUC) above 0.75, indicating good predictive performance. SHAP analysis revealed that the change of parent artery WSS contributed most significantly to accurate and early prediction. Additionally, a web application software was developed to assist clinicians in real-time aneurysm occlusion prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study developed a robust predictive model for UIA occlusion following FD treatment by integrating morphological and hemodynamic parameters, which may provide potentially valuable decision-making support for optimizing treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Inhibition of ADORA3 Promotes Microglial Phagocytosis and Alleviates Chronic Ischemic White Matter Injury”","authors":"","doi":"10.1111/cns.70326","DOIUrl":"https://doi.org/10.1111/cns.70326","url":null,"abstract":"<p>In Figure 6, the LFB-stained image in panel M was inadvertently replaced with an incorrect version during figure assembly; the correct version has been provided and does not affect the experimental findings.</p><p>We apologize for this error.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression-Like Behaviors Through Enhanced Synaptic Pruning in Male Mice","authors":"Wenhui Zhu,&nbsp;Jinlong Chang,&nbsp;Liusuyan Tian,&nbsp;Xiuyan Yang,&nbsp;Weifen Li","doi":"10.1111/cns.70394","DOIUrl":"https://doi.org/10.1111/cns.70394","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Microglia, as resident macrophages in the brain, play an important role in depression. Heat shock protein 60 (HSP60), as a chaperone protein, plays a role in cell stress. However, the role of microglial HSP60 in depression remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CX3CR1-CreER was used to generate microglial-specific HSP60 knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed to assess depression-like symptoms, microglial activation, and synaptic changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HSP60 cKO male mice exhibited depressive-like behaviors, without anxiety-like behavior, including increased immobility in the forced swimming and tail suspension tests, reduced sucrose preference, and elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation was confirmed by the increased expression levels of CD68 and CD86, the elevated transcription of the <i>cybb</i> gene, and reduced branch complexity. Enhanced phagocytosis of excitatory synapses, reduced dendritic spine density, and decreased glutamate levels were observed, with downregulation of synaptic proteins (AMPAR2, Synapsin-1, PSD95), indicating dysregulated synaptic pruning. Moreover, GO analysis showed 20 significant differentially expressed proteins (DEPs) from proteomics are associated with the presynaptic endosome, which plays a crucial role in maintaining synaptic function. Treatment with PLX3397, a CSF1R inhibitor, alleviated depressive-like behaviors and restored synaptic density in HSP60 cKO male mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HSP60 deletion in microglia leads to overactivation of microglia, impaired synaptic function, and depression-like behaviors, highlighting the importance of microglial homeostasis in mood regulation and the potential therapeutic role of microglial modulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alleviation of Microglia Mediating Hippocampal Neuron Impairments and Depression-Related Behaviors by Urolithin B via the SIRT1-FOXO1 Pathway","authors":"Cuilan Liu,&nbsp;Di Zhao,&nbsp;Guoxing Yu,&nbsp;HengWei Du,&nbsp;Lihong Xu,&nbsp;Yifan Cao,&nbsp;Minghu Cui,&nbsp;Wentao Wang,&nbsp;Dan Wang,&nbsp;Jing Liu,&nbsp;Fantao Meng,&nbsp;Fengai Hu,&nbsp;Wei Li,&nbsp;Jing Du,&nbsp;Chen Li","doi":"10.1111/cns.70379","DOIUrl":"https://doi.org/10.1111/cns.70379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Conventional antidepressants exhibit limited efficacy and delayed onset. This study aimed to elucidate the antidepressant effects of urolithin B (UB) and its regulatory role in microglia-mediated hippocampal neuronal dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The mouse model of depression was established using both chronic unpredicted stress (CUS) and lipopolysaccharide (LPS) injection. The therapeutic efficacy of UB was assessed through behavioral paradigms. The microglia activation, cellular cytotoxicity and apoptosis levels, and underlying molecular mechanisms were delineated utilizing proteomics analysis, immunofluorescence staining, real-time PCR and Western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UB efficiently alleviated depression-related behaviors, accompanied by suppressed microglia activation, neuroinflammation, changes of classic activation (M1)/alternative activation (M2) polarization and recovered sirtuin-1 (SIRT1) and forkhead box protein O1 (FOXO1) expression in the hippocampus. Additionally, UB reduced the cytotoxicity and apoptosis of HT22 cells and depression-related phenotypes treated by the cellular supernatant from LPS-incubated BV2 cells, which was mediated by the SIRT1-FOXO1 pathway. The proteomics analysis of the cellular supernatant content revealed abundant secreting proteins among the LPS/UB application.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study confirmed that microglial SIRT1 mediates UB's antidepressant effects, positioning UB as a promising therapeutic candidate for depression by targeting neuroinflammatory pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of Intranasally Administered rIL-10 Along the Olfactory Nerve and Perivascular Space After Intracerebral Hemorrhage","authors":"Shaoshuai Wang,&nbsp;Junmin Wang,&nbsp;Xinru Zhang,&nbsp;Shijun Xu,&nbsp;Qinfeng Peng,&nbsp;Yifei Li,&nbsp;Ruoqi Ding,&nbsp;Bing Jiang,&nbsp;Shuyu Wang,&nbsp;Shuaibing Zhang,&nbsp;Siyuan Hu,&nbsp;Yousef Rastegar-Kashkooli,&nbsp;Na Xing,&nbsp;Nan Li,&nbsp;Menglu Wang,&nbsp;Junyang Wang,&nbsp;Xuemei Chen,&nbsp;Chao Jiang,&nbsp;Xiaochong Fan,&nbsp;Jian Wang","doi":"10.1111/cns.70372","DOIUrl":"https://doi.org/10.1111/cns.70372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>The utilization of anti-inflammatory therapy for treating brain diseases holds promise; however, research on intranasal administration of drug compounds remains limited. Quantitative data, particularly pharmacokinetics, are scant, and direct evidence of the distribution of intranasally administered recombinant interleukin 10 (rIL-10) within the brain is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing fluorescent labeling, in vivo imaging, and confocal microscopy, we meticulously monitored the distribution and delivery pathways of intranasally administered rIL-10 in the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that rIL-10 can permeate the blood–brain barrier and reach the perihematomal area in the striatum of mice with intracerebral hemorrhage. Intranasally administered rIL-10 primarily targets the cerebral cortex, striatum, and thalamus, traversing the olfactory nerve pathway and perivascular space to access these brain regions. This mode of delivery effectively mitigated secondary brain injury after intracerebral hemorrhage. This study contributes to intranasal drug delivery research, offering compelling evidence to support the intranasal delivery of anti-inflammatory cytokines or alternative drug candidates for treating brain diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}