CNS Neuroscience & Therapeutics最新文献

{"title":"Plasma-Derived Exosomal i-tRF-LeuCAA as Biomarker for Glioma Diagnosis and Promoter of Epithelial-Mesenchymal Transition via TPM4 Regulation","authors":"Hongyu Liu,&nbsp;Wentao Hu,&nbsp;Lijun Zhang,&nbsp;Ze Li,&nbsp;Jialin Liu,&nbsp;Ling Chen","doi":"10.1111/cns.70356","DOIUrl":"https://doi.org/10.1111/cns.70356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to discover plasma-derived exosomal tsRNAs that serve as novel diagnostic biomarkers for glioma and to investigate the mechanism by which tsRNAs regulate glioma development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differentially expressed tsRNAs in the plasma exosomes of glioma patients were identified using small RNA array sequencing. Bioinformatics analyses were used to predict the biological function of tsRNAs. The changes in the phenotypes of glioma cells treated with a tsRNA mimic and inhibitor were detected. The diagnostic and prognostic characteristics of potential target genes and their related functions in gliomas were further analyzed. The cell and animal experiments were used to analyze the molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 453 differentially expressed tsRNAs identified in the plasma-derived exosomes of glioma patients using small RNA sequencing, i-tRF-LeuCAA was associated with the prognosis and molecular diagnostic characteristics of glioma patients and promoted the migration, invasion, and proliferation of glioma cells and inhibited their apoptosis. In addition, TPM4 is a potential target of i-tRF-LeuCAA and is related to epithelial–mesenchymal transition in gliomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>i-tRF-LeuCAA could be served as a non-invasive biomarker in the diagnosis and prognosis of glioma. i-tRF-LeuCAA may indirectly regulate TPM4 expression and influence epithelial–mesenchymal transition, which may promote glioma progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801331","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":"Efficacy and Potential Mechanisms of Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Ischemic Stroke in Animal Models: A Meta-Analysis","authors":"Renli Wei,&nbsp;Minguang Yang,&nbsp;Yue Cao,&nbsp;Shuqian Qiu,&nbsp;Xu Fan,&nbsp;Muxuan Fang,&nbsp;Li Chen,&nbsp;Shaojie Cheng,&nbsp;Jianhong Li,&nbsp;Shenghang Zhang","doi":"10.1111/cns.70357","DOIUrl":"https://doi.org/10.1111/cns.70357","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Umbilical cord-derived mesenchymal stem cells (UCMSCs) have emerged as a promising treatment for ischemic stroke. This study aimed to evaluate the therapeutic efficacy and potential mechanisms of UCMSCs in treating ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of PubMed, Web of Science, and Embase was conducted up to April 25, 2024. Literature was screened based on the PICOS principle, with predefined inclusion and exclusion criteria. Relevant data were extracted and analyzed using Review Manager 5.4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 1390 retrieved articles, 30 were included in the meta-analysis. UCMSCs significantly reduced infarct size and volume, improved neurological deficit scores, and facilitated neurobehavioral recovery. UCMSCs treatment also modulated inflammatory cytokine levels in brain tissue and serum, promoted microglial polarization, inhibited apoptosis, and increased vessel density in the peri-infarct tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>UCMSCs administration significantly promoted the neurological function recovery after ischemic stroke. Their mechanisms of action may be related to immune response regulation, inhibition of apoptosis, and promotion of angiogenesis. These findings provide theoretical guidance for improving the quality of basic research and clinical translation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801794","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":"Sevoflurane Inhibits the Proliferation of Neural Precursor Cells and Neural Migration of Mice by Inducing Iron Metabolism Disorders","authors":"Xincheng Li,&nbsp;Runjiao Cheng,&nbsp;Mahammad Naeem,&nbsp;Xiaoou Nie,&nbsp;Jiaqi Wang,&nbsp;Liqiang Zhao,&nbsp;Xiaopeng Liu,&nbsp;Zhenhua Shi,&nbsp;Jianhua Zhang","doi":"10.1111/cns.70369","DOIUrl":"https://doi.org/10.1111/cns.70369","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sevoflurane (Sev) is a volatile anesthetic and inhibits the proliferation of neural precursor cells (NPCs) and neuronal migration in the embryonic brain, thereby affecting offspring's cortical development and cognitive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pregnant mice were treated with 2.5% Sev. In utero, plasmids with GFP were electroporated into embryonic cortical neural precursor cells. Cell proliferation and neurite growth were detected by immunofluorescence of Ki67, pH 3, BrdU, Map2, and phalloidin labeling, respectively. Ferritin, transferrin receptor1 (TfR1), and confilin were detected by western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sev inhibited the proliferation of NPCs by down-regulating the expression of pH 3 and Ki67, and also delayed the radial migration of cortical neurons. Sev impaired the multipolar-to-bipolar transition of migrating neurons by affecting Golgi orientation. Furthermore, Sev down-regulated the expression of TfR1and increased the protein levels of ferritin heavy chain (FtH) and ferritin light chain (FtL) and caused the iron accumulation in the brain. Meanwhile, Sev induced the abnormal depolymerization and polymerization of microfilaments by increasing the ratio of p-Cofilin/Cofilin and decreasing the ratio of F-actin/G-actin. Meanwhile, Sev inhibited cortical development by decreasing the neurite growth and number of branches of neurites. DFO, an iron-chelating agent, could significantly ameliorate the inhibitory effect of Sev on the proliferation of NPCs and radial migration of projection neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sev inhibited the NPCs proliferation and neuronal migration by inducing iron metabolic dysfunction. Regulating iron homeostasis could protect the cortical development of the embryo against Sev exposure during pregnancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801876","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":"Elucidating the Role of Trem2 in Lipid Metabolism and Neuroinflammation","authors":"Chenhui Zhao,&nbsp;Wei Qi,&nbsp;Xiaoping Lv,&nbsp;Xueli Gao,&nbsp;Chaonan Liu,&nbsp;Shimin Zheng","doi":"10.1111/cns.70338","DOIUrl":"https://doi.org/10.1111/cns.70338","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuroinflammation. Astrocytes play a key role in the neuroinflammatory environment of AD, especially through lipid metabolism regulation. However, the mechanisms by which astrocytes, particularly through the triggering receptor expressed on myeloid cells 2 (Trem2) receptor, contribute to lipid dysregulation and neuroinflammation in AD remain inadequately understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed an AD mouse model and integrated single-cell RNA sequencing (scRNA-seq), transcriptomics, and high-throughput metabolomics to analyze lipid metabolism and inflammatory profiles in astrocytes. Differential gene expression was further validated with the GEO database, and in vitro and in vivo experiments were conducted to assess the impact of Trem2 modulation on astrocytic inflammation and lipid composition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings demonstrate that Trem2 modulates lipid metabolism in astrocytes, affecting fatty acid and phospholipid pathways. In the AD model, Trem2 expression was suppressed, enhancing nuclear factor-κB (NF-κB) signaling and promoting the secretion of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Trem2 overexpression reduced astrocytic inflammation and altered lipid composition, attenuating neuroinflammation both in vitro and in vivo. These results underscore Trem2's regulatory role in lipid metabolism and its significant impact on neuroinflammation in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identifies Trem2 as a pivotal regulator of astrocytic lipid metabolism and neuroinflammation in AD, providing potential molecular targets for early intervention and therapeutic strategies aimed at mitigating AD progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809392","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":"Efficacy and Potential Mechanism of Chinese Herbal Formula Chaihu Shugan Powder on Animal Models of Depression: A Systematic Review and Meta-Analysis","authors":"Lulu Wu,&nbsp;Yi Deng,&nbsp;Liyuan Yu,&nbsp;Weihang Peng,&nbsp;Ya Li,&nbsp;Yuchao Feng,&nbsp;Li Chen,&nbsp;Peiying Huang,&nbsp;Bojun Chen","doi":"10.1111/cns.70375","DOIUrl":"https://doi.org/10.1111/cns.70375","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chaihu Shugan powder (CSP) is used in the clinical treatment of depression. However, its clinical mechanisms remain elusive. While acknowledging the extensive animal research, there is a need for systematic meta-analysis for comprehensive understanding. This study aims to evaluate the efficacy of CSP and its mechanisms in animal models of depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Animal studies on the antidepressant effects of CSP were reviewed in databases including PubMed, Web of Science, Cochrane Library, Embase database, CNKI, VIP, WangFang database, and CBM published before March 12, 2024. The R Studio software was used for statistical analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The present systematic review included 23 studies. The results revealed that CSP has a significant effect on behavior forced swimming test (FST) (SMD = −1.44, 95% CI: −1.87, −1.00); sucrose preference test (SPT) (SMD = 3.63, 95% CI: 1.87, 5.39), rearing numbers of open field test (OFT) (SMD = 1.46, 95% CI: 0.95, 1.96); crossing numbers of OFT (SMD = 2.15, 95% CI: 1.30, 3.01); and body weight (SMD = 2.16, 95% CI: 1.13, 3.18).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, this study revealed that CSP could treat depression symptoms in animals, which is associated with its anti-inflammatory effects, regulation of the HPA axis, neurotrophic factors, and glucose metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801812","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":"Identification of Common Brain Protein and Genetic Loci Between Parkinson's Disease and Lewy Body Dementia","authors":"Tingting Jia,&nbsp;Fuhua Yang,&nbsp;Fengqin Qin,&nbsp;Yongji He,&nbsp;Feng Han,&nbsp;Chengcheng Zhang","doi":"10.1111/cns.70370","DOIUrl":"https://doi.org/10.1111/cns.70370","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) and Lewy body dementia (LBD) have many common features, including clinical manifestations, neurochemistry, and pathology, but little is known about their shared brain proteins and genetic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To identify susceptibility-related brain proteins that are shared between PD and LBD patients, proteome-wide association studies (PWASs) were conducted by integrating human brain protein quantitative trait loci (pQTLs) with large-scale genome-wide association studies (GWASs) of both diseases. Subsequently, pleiotropy-informed conditional false discovery rate (pleioFDR) analysis was performed to identify common risk genetic loci between PD and LBD. Finally, the downregulation of these risk genes in different disease states was validated by differential gene expression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PWASs identified 12 PD risk proteins and nine LBD risk proteins, among which <i>TMEM175</i> (<i>z</i>_PD = −7.25, <i>P</i>_PD = 4.12E-13; <i>z</i>_LBD = −6.02, <i>P</i>_LBD = 1.75E-09) and <i>DOC2A</i> (<i>z</i>_PD = −4.13, <i>P</i>_PD = 3.71E-05; <i>z</i>_LBD = −3.91, <i>P</i>_LBD = 9.08E-05) were shared. PleioFDR analysis revealed that five genetic risk loci mapped to eight genes associated with PD and LBD, including the proteome-wide significant risk gene <i>TMEM175</i> (ConjFDR = 5.74E-03). Differential expression analysis verified that <i>TMEM175</i> was significantly downregulated in the midbrains of PD patients (<i>p</i> = 1.19E-02), and further exploration revealed that <i>TMEM175</i> was also dramatically downregulated in the substantia nigra of PD patients (<i>p</i> = 1.16E-02) and incidental Lewy body disease patients (<i>p</i> = 7.52E-03). Moreover, <i>TMEM175</i> was significantly downregulated in induced pluripotent stem cell-derived dopaminergic neurons from PD patients (<i>p</i> = 4.60E-02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dysregulation of <i>TMEM175</i> may confer PD and LBD risk and may be partly responsible for their comorbidity. Our results revealed the common genetic risk factors between PD and LBD, which elucidated the shared genetic basis of these diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801400","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":"Single-Cell Profiling and Proteomics-Based Insights Into mTORC1-Mediated Angio+TAMs Polarization in Recurrent IDH-Mutant Gliomas","authors":"Xu Wang,&nbsp;Jingyan Gu,&nbsp;Hongyu Tang,&nbsp;Lianping Gu,&nbsp;Yunke Bi,&nbsp;Yue Kong,&nbsp;Qiao Shan,&nbsp;Jian Yin,&nbsp;Meiqing Lou,&nbsp;Shouwei Li,&nbsp;Yaohua Liu","doi":"10.1111/cns.70371","DOIUrl":"https://doi.org/10.1111/cns.70371","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;IDH mutant gliomas often exhibit recurrence and progression, with the mTORC1 pathway and tumor-associated macrophages potentially contributing to these processes. However, the precise mechanisms are not fully understood. This study seeks to investigate these relationships using proteomic, phosphoproteomic, and multi-dimensional transcriptomic approaches.&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;This study established a matched transcriptomic, proteomic, and phosphoproteomic cohort of IDH-mutant gliomas with recurrence and progression, incorporating multiple glioma-related datasets. We first identified the genomic landscape of recurrent IDH-mutant gliomas through multi-dimensional differential enrichment, GSVA, and deconvolution analyses. Next, we explored tumor-associated macrophage subpopulations using single-cell sequencing in mouse models of IDH-mutant and wild-type gliomas, analyzing transcriptional changes via AddmodelScore and pseudotime analysis. We then identified these subpopulations in matched primary and recurrent IDH-mutant datasets, investigating their interactions with the tumor microenvironment and performing deconvolution to explore their contribution to glioma progression. Finally, spatial transcriptomics was used to map these subpopulations to glioma tissue sections, revealing spatial co-localization with mTORC1 and angiogenesis-related pathways.&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;Multi-dimensional differential enrichment, GSVA, and deconvolution analyses indicated that the mTORC1 pathway and the proportion of M2 macrophages are upregulated during the recurrence and progression of IDH-mutant gliomas. CGGA database analysis showed that mTORC1 activity is significantly higher in recurrent IDH-mutant gliomas compared to IDH-wildtype, with a correlation to M2 macrophage infiltration. KSEA revealed that AURKA is enriched during progression, and its inhibition reduces mTORC1 pathway activity. Single-cell sequencing in mouse models identified a distinct glioma subpopulation with upregulated mTORC1, exhibiting both M2 macrophage and angiogenesis transcriptional features, which increased after implantation of IDH-mutant tumor cells. Similarly, human glioma single-cell data revealed the same subpopulation, with cell–cell communication analysis showing active VEGF signaling. Finally, spatial transcriptomics deconvolution confirmed the co-localization of this subpopulation with mTORC1 and VEGFA in high-grade IDH-mutant gliomas.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findin","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801333","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":"Sanshen San Formula Hinders Cognitive Function and Pathology in Alzheimer's Disease Through Potentiating the Function of Synapse","authors":"Shiquan Chang,&nbsp;Nana Ding,&nbsp;Yalin Li,&nbsp;Ying Li,&nbsp;Ziling Tang,&nbsp;Junping Pan,&nbsp;Li Yan,&nbsp;Jiaxu Chen","doi":"10.1111/cns.70349","DOIUrl":"https://doi.org/10.1111/cns.70349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) constitutes a devastating neurodegenerative disorder, manifested by amyloid-β aggregation, phosphorylated tau accumulation, and progressive cognitive deterioration. Current therapeutic interventions remain predominantly symptomatic, underscoring the urgency for more efficacious treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study elucidated the therapeutic potential of Sanshen San (SSS), a traditional Chinese herbal formula encompassing <i>Polygala Radix</i>, <i>Pini Radix in Poria</i>, and <i>Acori Tatarinowii Rhizoma</i>, on cognitive function and AD pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We implemented both acute Aβ_1-42-injected mice and 5xFAD transgenic mouse models. The therapeutic efficacy of SSS was assessed through behavioral paradigms including Y-maze, Novel Object Recognition, and Morris Water Maze. Molecular mechanisms were delineated utilizing RNA sequencing, metabolomics analysis, immunofluorescence staining, Golgi-Cox staining, transmission electron microscopy, and Western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chemical analysis unveiled 10 principal bioactive compounds in SSS. The formula substantially ameliorated cognitive performance in both Aβ_1-42-injected and 5xFAD mouse models, attenuated Aβ plaque burden, and augmented microglial phagocytosis. SSS safeguarded synaptic integrity, enhanced mitochondrial function, and facilitated autophagy. Transcriptomic and metabolomic analyses demonstrated that SSS predominantly operates by reinstating synaptic transmission and neurotransmitter function, particularly in the dopaminergic system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SSS efficaciously mitigates AD pathology through potentiating synaptic function, optimizing mitochondrial homeostasis, and restoring neurotransmitter balance, exemplifying a promising multi-target therapeutic strategy for the treatment of AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801799","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":"Psychoeducational Program Increases Telomerase Activity in Bipolar Disorder: A Gender-Based Randomized Controlled Trial","authors":"G. Massa,&nbsp;F. Bruno,&nbsp;L. Tarsitani,&nbsp;M. Caredda,&nbsp;M. Biondi,&nbsp;A. Bevilacqua,&nbsp;S. Canterini","doi":"10.1111/cns.70292","DOIUrl":"https://doi.org/10.1111/cns.70292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This randomized controlled trial evaluated the efficacy of a psychoeducational program in enhancing telomerase activity (TA) among patients with bipolar disorder (BD), with a specific focus on gender differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 62 participants were assigned to either the psychoeducation (PE) group or the control (CTR) group, with TA measured both before and after the intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results demonstrated a significant increase in TA in the PE group compared to the controls at the conclusion of the study. Notably, gender-specific analyses revealed that female participants showed significant increases in both TA and delta TA (Δ_TA), with Δ_TA PE = 0.586 ± 0.273 and Δ_TA CTR = −0.251 ± 0.177. In contrast, male participants exhibited significant changes only in Δ_TA, with Δ_TA PE = 0.257 ± 0.138 and Δ_TA CTR = −0.144 ± 0.1194.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that psychoeducational interventions have differential gender-specific effects, underscoring the importance of personalized approaches in the treatment of BD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809393","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":"Phosphorylation of cAMP-Activated Exchange Protein-1 Participates in Neuroprotection and Ferroptosis Regulation Following Intracerebral Hemorrhage in Rats","authors":"Guannan Jiang,&nbsp;Jialei Zhou,&nbsp;Yan Zhuang,&nbsp;Siyuan Yang,&nbsp;Gang Chen,&nbsp;Wanchun You,&nbsp;Xiang Li","doi":"10.1111/cns.70373","DOIUrl":"https://doi.org/10.1111/cns.70373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intracerebral hemorrhage (ICH) is a severe condition characterized by elevated mortality and disability rates. The cAMP-activated exchange protein-1 (EPAC-1) is implicated in various cytoprotective mechanisms; however, its specific role in ICH remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A rat model of ICH was established by injecting autologous blood, while the in vitro primary neuronal model was stimulated using oxyhemoglobin (OxyHb). The construction of EPAC-1 overexpression wild-type (WT) and phosphorylated mutant plasmids (S108A or S108E), as well as lentiviruses, was performed for in vitro and in vivo studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cAMP signaling pathway was found to be significantly enriched following ICH by high-throughput sequencing analysis. Our findings showed that while EPAC-1 protein levels remained relatively unchanged after ICH, RabGEF activity was conspicuously upregulated. This was accompanied by a marked decrease in EPAC-1 phosphorylation levels. Mutations that activate EPAC-1 phosphorylation led to significant improvements in neuronal survival and behavioral outcomes after ICH. Bioinformatics analysis revealed that ferroptosis was significantly enriched after ICH and showed a positive correlation with EPAC-1 serine phosphorylation. EPAC-1 phosphorylation activating mutations inhibit neuronal ferroptosis, whereas inactivating mutations exacerbate it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The phosphorylation of EPAC-1 is essential for maintaining neuronal survival, which may be related to ferroptosis inhibition after ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801399","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}