CNS Neuroscience & Therapeutics最新文献

{"title":"Exploring the Synergistic Effects of Erinacines on Microglial Regulation and Alzheimer's Pathology Under Metabolic Stress","authors":"Van Thanh Bui,&nbsp;Kuan-Wei Wu,&nbsp;Chin-Chu Chen,&nbsp;Anh Thuc Nguyen,&nbsp;Wei-Jan Huang,&nbsp;Li-Ya Lee,&nbsp;Wan-Ping Chen,&nbsp;Chi-Ying Huang,&nbsp;Young-Ji Shiao","doi":"10.1111/cns.70137","DOIUrl":"10.1111/cns.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Hericium erinaceus</i> mycelium and its constituents, erinacines A and S, have shown neuroprotective effects in APP/PS1 transgenic mice; however, the precise mechanisms by which they modulate microglial phenotypes remain unclear. Our study is the first to explore the effect of erinacines on microglia morphology and the underlying mechanisms using a novel primary mixed glia cell model and advanced bioinformatic tools. Furthermore, we emphasize the clinical relevance by evaluating erinacines in a metabolically stressed APP/PS1 mouse model, which more accurately reflects the complexities of human Alzheimer's disease (AD), where metabolic syndrome is a common comorbidity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rat primary mixed glial cultures were used to simulate the spectrum of microglial phenotypes, particularly the transition from immature to mature states. Microarray sequencing, along with Connectivity Map, ConsensusPathDB, and Gene Set Enrichment Analysis, identified pathways influenced by erinacines. The therapeutic efficacy was further evaluated in metabolically stressed APP/PS1 mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Erinacines significantly promoted the development of a ramified, neuroprotective microglial phenotype. Bioinformatics revealed potential modulation of microglia via histone deacetylase inhibition, actin filament dynamics, and synaptic structure modification—pathways not previously linked to erinacines in AD. Importantly, erinacines significantly lower fasting blood glucose and insulin levels while reducing amyloid-beta plaque burden, suppressing hyperactivated glial responses, and enhancing neurogenesis in the metabolically stressed APP/PS1 mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrate the dual action of erinacines in modulating microglia morphology and phenotype while providing neuroprotection in a model that closely mimic the complexities of human Alzheimer's disease. Additionally, this study provides the foundation for understanding the potential mechanisms of action of erinacines, highlighting their promise as a novel treatment approach for Alzheimer's, particularly in cases complicated by metabolic dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845358","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":"Microglial Mayhem NLRP3 Inflammasome's Role in Multiple Sclerosis Pathology","authors":"Hua Fan,&nbsp;Qizhi Fu,&nbsp;Ganqin Du,&nbsp;Ling Qin,&nbsp;Xiaofei Shi,&nbsp;Dongmei Wang,&nbsp;Yanhui Yang","doi":"10.1111/cns.70135","DOIUrl":"10.1111/cns.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This review delves into the intricate relationship between NLR inflammasomes, particularly the NLRP3 inflammasome, and the immune-mediated neurodegenerative disease, multiple sclerosis (MS). While the precise etiology of MS remains elusive, compelling research underscores the pivotal role of the immune response in disease progression. Notably, recent investigations highlight the significant involvement of NLRP3 inflammasomes in various autoimmune diseases, prompting an in-depth exploration of their impact on MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The review focuses on elucidating the activation mechanism of NLRP3 inflammasomes within microglia/macrophages (MG/MФ), examining how this activation promotes an inflammatory response that exacerbates neuronal damage in MS. A comprehensive analysis of existing literature and research findings forms the basis for understanding the intricate interplay between NLRP3 inflammasomes and MS pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Synthesizing current research, the review provides insight into the pivotal role played by NLR inflammasomes, specifically NLRP3, in MS. Emphasis is placed on the inflammatory response orchestrated by activated MG/MФ, elucidating the cascade that perpetuates neuronal damage in the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review concludes by consolidating key findings and offering a nuanced perspective on the role of NLRP3 inflammasomes in MS pathogenesis. The detailed exploration of the activation process within MG/MФ provides a foundation for understanding the disease's underlying mechanisms. Furthermore, the review sets the stage for potential therapeutic strategies targeting NLRP3 inflammasomes in the pursuit of MS treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845388","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":"tsRNAs: A Prospective, Effective Therapeutic Intervention for Neurodegenerative Diseases","authors":"Tianqi Li,&nbsp;Hui Zhen,&nbsp;Weiwei Wu,&nbsp;Fengtang Yang,&nbsp;Zhonghong Cao","doi":"10.1111/cns.70177","DOIUrl":"10.1111/cns.70177","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurological disorders known as neurodegenerative diseases (NDDs) result in the slow loss of neurons in the central nervous system (CNS) or peripheral nervous system (PNS), as well as the collapse of neural networks in terms of structure and function. NDDs are expected to surpass cancer as the second biggest cause of mortality by 2040, according to World Health Organization (WHO) estimations. Neurons cannot effectively regenerate themselves because they are terminally differentiated. Accordingly, it is challenging to find medications that could stop or slow neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main body</h3>\u0000 \u0000 <p>The tsRNAs are a type of small non-coding RNAs derived from mature tRNAs or tRNA precursors. tsRNAs control gene expression and have a role in many physiological and pathological processes, including neurological illnesses. Antisense oligonucleotides are effective therapeutic agents for neurological diseases, and they may be the treatment of choice for neurodegenerative diseases in the future. Here, we review the biogenesis of tsRNA, its physiological and pathological functions in the central nervous system and neurological disorders, and its prospective use as a nucleic acid medication to treat NDDs, providing theoretical support and guidance for further exploration of tsRNAs in therapeutic intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>tsRNAs are emerging as important regulatory molecules in neurodegenerative diseases. Understanding the functions of tsRNAs in neurodegenerative diseases may provide new insights into disease mechanisms and lead to the development of novel treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845412","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":"Functional Segregation-Integration Preference Configures the Cognitive Decline Against Cerebral Small Vessel Disease: An MRI Study","authors":"Wentao Hu,&nbsp;Yao Wang,&nbsp;Zhenhui Xie,&nbsp;Mianxin Liu,&nbsp;Xu Han,&nbsp;Ying Hu,&nbsp;Xingrui Wang,&nbsp;Yongming Dai,&nbsp;Qun Xu,&nbsp;Yan Zhou","doi":"10.1111/cns.70162","DOIUrl":"10.1111/cns.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cerebral small vessel disease (CSVD) is highly prevalent in elder individuals, and its variable cognitive outcomes indicate some cognitive reserve mechanisms. Contribution from functional network features is still unclear. Here we explore how functional segregation-integration preference influences the cognitive changes against CSVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A total of, 271 CSVD patients were included, all underwent MRI scans including routine and resting-state functional MRI (rs-fMRI). Hierarchical balance index (<i>H</i>_<i>B</i>) was obtained from the rs-fMRI connectivity using eigenmode-based approach. Individuals were classified into segregated and integrated groups according to negative and positive <i>H</i>_<i>B</i>. A composite CSVD lesion score was calculated from imaging findings. Global and five specific cognitive functions were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hierarchical regression analysis revealed negative contribution from lesion load to global and all cognitive domains (<i>β</i> = −0.22~−0.35, ∆<i>R</i>² = 0.046~0.112, all <i>p</i> &lt; 0.001). Inclusion of <i>H</i>_<i>B</i> did not show significant contribution (all <i>p</i> &gt; 0.05), but interaction between <i>H</i>_<i>B</i> and lesion score was significantly associated with global (<i>β</i> = −0.27, ∆<i>R</i>² = 0.013, <i>p</i> = 0.034) and execution score (<i>β</i> = −0.34, ∆<i>R</i>² = 0.023, <i>p</i> = 0.002). Integrated patients show significant better global cognitive (23.9 ± 3.9 vs. 25.5 ± 3.1, <i>p</i> = 0.044) and executive ability (0.235 ± 0.678 vs. 0.535 ± 0.688, <i>p</i> = 0.049) at mild damage stage, visuospatial (−0.001 ± 0.804 vs. 0.379 ± 0.249, <i>p</i> = 0.034) and language ability (−0.133 ± 0.849 vs. 0.218 ± 0.704, <i>p</i> = 0.037) at moderate damage stage. Cross-overs of cognitive scores were observed. Significant better execution (−0.277 ± 0.717 vs. −0.675 ± 0.883, <i>p</i> = 0.027) was found in severe damage stage for segregated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, we concluded that integrated network contributes to cognitive resilience in mild and moderate but not in severe damage stages.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845367","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":"Oligodendrocyte Progenitor Cell Transplantation Reduces White Matter Injury in a Fetal Goat Model","authors":"Yan Yue,&nbsp;Bixin Deng,&nbsp;Yan Zeng,&nbsp;Wenxing Li,&nbsp;Xia Qiu,&nbsp;Peng Hu,&nbsp;LiuHong Shen,&nbsp;Tiechao Ruan,&nbsp;Ruixi Zhou,&nbsp;Shiping Li,&nbsp;Junjie Ying,&nbsp;Tao Xiong,&nbsp;Yi Qu,&nbsp;Zuo Luan,&nbsp;Dezhi Mu","doi":"10.1111/cns.70178","DOIUrl":"10.1111/cns.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preterm white matter injury (PWMI) is the most common type of brain injury in preterm infants, in which, oligodendrocyte progenitor cells (OPCs) are predominantly damaged. In this study, human OPCs (hOPCs) were administered to a fetal goat model of PWMI to examine the differentiation potential and therapeutic effects of the cells on PWMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Preterm goat fetuses were subjected to hypoxic-ischemia (HI) via intermittent umbilical cord occlusion (5 min × 5). Twenty million hOPCs were administered via a nasal catheter 12 h after an HI insult, and brain tissues were collected 14 or 21 days after the HI insult. Myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) were detected by immunofluorescence and western blotting techniques. The percentage of myelinated nerve fibers and g-ratio were examined using transmission electron microscopy. Inflammatory cells were detected by immunohistochemistry. Inflammatory and neurotrophic factors were measured using enzyme-linked immunosorbent assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that intermittent umbilical cord occlusion induced PWMI in fetal goats. Transplanted hOPCs can survive in periventricular and subcortical white matter. Further, transplanted hOPCs expressed markers of mature oligodendrocytes (MBP and MAG) and few cells expressed markers of preoligodendrocytes (NG2 and A2B5), suggesting that these cells can differentiate into mature oligodendrocytes in the brain. In addition, hOPCs administration increased MBP and MAG levels, percentage of myelinated nerve fibers, and thickness of the myelin sheath, indicating a reduction in PWMI. Furthermore, hOPCs did not increase the inflammatory response after HI. Interestingly, hOPC administration decreased tumor necrosis factor-alpha and increased glial-derived neurotrophic factor and brain-derived neurotrophic factor levels after HI, suggesting that additional mechanisms mediate the inflammatory microenvironment and neuroprotective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Exogenous hOPCs can differentiate into mature oligodendrocytes in fetal goats and alleviate HI-induced PWMI. Transplantation of hOPCs is a promising strategy for treating PWMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845393","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":"The Oral–Gut–Brain Axis: The Influence of Microbes as a Link of Periodontitis With Ischemic Stroke","authors":"Yi Zhong,&nbsp;Xianhui Kang,&nbsp;Xiaofeng Bai,&nbsp;Bei Pu,&nbsp;Daniel Smerin,&nbsp;Liang Zhao,&nbsp;Xiaoxing Xiong","doi":"10.1111/cns.70152","DOIUrl":"10.1111/cns.70152","url":null,"abstract":"<p>Periodontitis, a non-communicable chronic inflammation disease resulting from dysbiosis of the oral microbiota, has been demonstrated to have a positive association with the risk of ischemic stroke (IS). The major periodontal pathogens contribute to the progression of stroke-related risk factors such as obesity, diabetes, atherosclerosis, and hypertension. Transcriptional changes in periodontitis pathogens have been detected in oral samples from stroke patients, suggesting a new conceptual framework involving microorganisms. The bidirectional regulation between the gut and the central nervous system (CNS) is mediated by interactions between intestinal microflora and brain cells. The connection between the oral cavity and gut through microbiota indicates that the oral microbial community may play a role in mediating complex communication between the oral cavity and the CNS; however, underlying mechanisms have yet to be fully understood. In this review, we present an overview of key concepts and potential mechanisms of interaction between the oral–gut–brain axis based on previous research, focusing on how the oral microbiome (especially the periodontal pathogens) impacts IS and its risk factors, as well as the mediating role of immune system homeostasis, and providing potential preventive and therapeutic approaches.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826964","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":"Reproductive Toxicity Induced by Serotonin-Norepinephrine Reuptake Inhibitors: A Pharmacovigilance Analysis From 2004 to 2023 Based on the FAERS Database","authors":"Yujia Xi,&nbsp;Zhuocheng Bao,&nbsp;Qiang Guo,&nbsp;Jingqi Wang,&nbsp;Zhinan Jing,&nbsp;Jingkai Di,&nbsp;Ke Yang","doi":"10.1111/cns.70176","DOIUrl":"10.1111/cns.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Serotonin-norepinephrine reuptake inhibitors (SNRIs) have been extensively utilized for the treatment of depression and anxiety disorders. Clinical trials and real-world data suggest that SNRIs may cause reproductive toxicity. To comprehensively assess this association, we conducted a pharmacovigilance study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized various disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to assess the significance of reproductive toxicity-related adverse events (AEs) reported to FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2023, with subgroup analysis conducted by sex and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Duloxetine and venlafaxine were associated with 14 and 25 AE signals related to reproductive toxicity, respectively, with erectile dysfunction (ED) and retrograde ejaculation identified as shared important medical events (IMEs). ED had the highest reporting frequency, strongest in venlafaxine-treated patients under 45 years (ROR 4.34, PRR 4.33, IC 2.09, EBGM 4.25). Retrograde ejaculation was newly identified. With decreasing incidence, venlafaxine's median ED onset was 122.5 days and duloxetine's 38 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides evidence through an extensive analysis of the large-scale real-world FAERS database, aiding healthcare professionals in mitigating, and prioritizing SNRI-related reproductive toxicity AEs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816812","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":"Caffeine's Neuroprotective Effect on Memory Impairment: Suppression of Adenosine A2A Receptor and Enhancement of Tyrosine Hydroxylase in Dopaminergic Neurons Under Hypobaric Hypoxia Conditions","authors":"Zhifeng Zhong,&nbsp;Huaping Dong,&nbsp;Simin Zhou,&nbsp;Chaoqun Lin,&nbsp;Pei Huang,&nbsp;Xiaoxu Li,&nbsp;Jijian Zhang,&nbsp;Jiaxin Xie,&nbsp;Yu Wu,&nbsp;Peng Li","doi":"10.1111/cns.70134","DOIUrl":"10.1111/cns.70134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Chronic hypobaric hypoxia frequently results in memory deficits, with severe cases showing marked alterations in dopamine levels and its metabolites. This research explores caffeine's modulation of the adenosine A₂A receptor (A₂AR) and its regulatory effects on tyrosine hydroxylase (TH), aiming to restore dopamine homeostasis and mitigate memory impairments associated with hypoxia. The goal is to identify novel preventive strategies against cognitive decline induced by hypoxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Network pharmacological analysis was employed to predict the interactions between caffeine, cognitive function, and hypobaric hypoxia-related disorders. The novel object recognition and Y-maze tests were utilized to assess caffeine's impact on memory deficits under hypobaric hypoxia conditions in male mice. LC–MS/MS analysis was subsequently conducted to examine the variations in dopamine and its metabolites within the midbrain. Molecular docking further confirmed the binding affinities between A₂AR and caffeine, as well as TH and caffeine. Additionally, immunofluorescence and protein-protein docking were employed to elucidate the interaction between A₂AR and TH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings highlight the pivotal role of adenosine receptors and dopamine-related pathways in the interplay between caffeine, cognition, and hypobaric hypoxia-related disorders. Behavioral tests demonstrated that caffeine effectively alleviated memory impairments caused by chronic hypobaric hypoxia. LC–MS/MS results revealed significant differences in dopamine, metanephrine, and 3-hydroxyanthranilic acid levels following caffeine treatment for hypoxia-induced cognitive deficits. Molecular docking confirmed the high affinity between A₂AR and caffeine, as well as TH and caffeine, while immunofluorescence and protein–protein docking provided insights into the A₂AR-TH interaction and its modulation during hypobaric hypoxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Caffeine exhibits potent neuroprotective effects against chronic high-altitude-induced cognitive impairments, potentially through its action on A₂AR, leading to enhanced TH expression and subsequent release of dopamine and its related neurotransmitters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816864","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":"Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury","authors":"Yulin Zhao,&nbsp;Zhengchao Wu,&nbsp;Yuchen Zhou,&nbsp;Cheng Chen,&nbsp;Yang Lu,&nbsp;Heng Wang,&nbsp;Tao Xu,&nbsp;Changwei Yang,&nbsp;Xiaoqing Chen","doi":"10.1111/cns.70163","DOIUrl":"10.1111/cns.70163","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In recent years, the utilization of stem cell therapy and cell sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, the most appropriate cell type and mechanism of action remain unclear at this time. This study sought to develop an SCI rat model and evaluate the therapeutic effects of human umbilical cord mesenchymal stem cell (hUC-MSC) sheets in this model. Furthermore, the mechanisms underlying the vascular repair effect of hUC-MSC sheets following SCI were investigated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A temperature-responsive cell culture method was employed for the preparation of hUC-MSC sheets. The extracellular matrix (ECM) produced by hUC-MSCs serves two distinct yet interrelated purposes. Firstly, it acts as a biologically active scaffold for transplanted cells, facilitating their attachment and proliferation. Secondly, it provides mechanical support and bridges spinal cord stumps, thereby facilitating the restoration of spinal cord function. The formation of the cavity within the spinal cord was evaluated using the Hematoxylin and Eosin (H&amp;E) staining method. Subsequently, endothelial cells were cultivated with the conditioned medium (CM) obtained from hUC-MSCs or hUC-MSC sheets. The pro-angiogenic impact of the conditioned medium of hUC-MSCs (MSC-CM) and the conditioned medium of hUC-MSC sheets (CS-CM) was evaluated through the utilization of the CCK-8 assay, endothelial wound healing assay, and tube formation assay in an in vitro context. The development of glial scars, blood vessels, neurons, and axons in hUC-MSCs and hUC-MSC sheets was assessed through immunofluorescence staining.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In comparison to hUC-MSCs, hUC-MSC sheets demonstrated a more pronounced capacity to facilitate vascular formation and induce the regeneration of newborn neurons at the SCI site, while also reducing glial scar formation and significantly enhancing motor function in SCI rats. Notably, under identical conditions, the formation of cell sheets has been associated with a paracrine increase in the ability of the cells themselves to secrete pro-angiogenic growth factors. During the course of the experiment, it was observed that the secretion of uPAR was the most pronounced among the pro-angiogenic factors present in MSC-CM and CS-CM. This finding was subsequently corroborated in subsequent experiments, wherein uPAR was demonstrated to promote angiogenesis via the PI3K/Akt signaling pathway.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816866","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":"CCN1 Promotes Mesenchymal Phenotype Transition Through Activating NF-κB Signaling Pathway Regulated by S100A8 in Glioma Stem Cells","authors":"Xing Guo,&nbsp;Shuhua Guo,&nbsp;Feng Tian,&nbsp;Zijie Gao,&nbsp;Yang Fan,&nbsp;Chuanxin Wang,&nbsp;Shuo Xu","doi":"10.1111/cns.70128","DOIUrl":"10.1111/cns.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The presence of glioma stem cells (GSCs) and the occurrence of mesenchymal phenotype transition contribute to the miserable prognosis of glioblastoma (GBM). Cellular communication network factor 1 (CCN1) is upregulated within various malignancies and associated with cancer development and progression, while the implications of CCN1 in the phenotype transition and tumorigenicity of GSCs remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data for bioinformatic analysis were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. A range of primary GBM and GSC cell models were then used to demonstrate the regulatory role of CCN1 via the phenotype validation, tumor sphere formation assays, extreme limiting dilution assays (ELDA), and transwell assays. To screen out the downstream signaling pathway, we employed high-throughput RNA-seq. Intracranial xenograft GSC mouse models were used to investigate the role of CCN1 in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the CCN family members, CCN1 was highly expressed in MES-GBM/GSCs and was correlated with a poor prognosis. Both in vitro and in vivo assays indicated that knockdown of CCN1 in MES-GSCs reduced the tumor stemness, proliferation, invasion, and tumorigenicity, whereas CCN1 overexpression in PN-GSCs exhibited the opposite effects. Mechanistically, CCN1 triggered the FAK/STAT3 signaling in autocrine and paracrine manners to upregulate the expression of S100A8. Knockdown of S100A8 inactivated NF-κB/p65 pathway and significantly suppressed the tumorigenesis of MES-GSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings reveal that CCN1 may be an important factor in the enhanced invasiveness and MES phenotype transition of GSCs and highlight the potential to target CCN1 for treating GBM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805662","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}