CNS Neuroscience & Therapeutics最新文献

{"title":"What We Know About TMEM175 in Parkinson's Disease","authors":"Jing Wang,&nbsp;Xuechun Sun,&nbsp;Lufeng Cheng,&nbsp;Meijie Qu,&nbsp;Chanyuan Zhang,&nbsp;Xueting Li,&nbsp;Lingyan Zhou","doi":"10.1111/cns.70195","DOIUrl":"10.1111/cns.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lysosome is a highly heterogeneous membranous organelle in eukaryotic cells, which regulates many physiological processes in the cell. Studies have found that lysosomal dysfunction disrupts cellular homeostasis and is associated with Parkinson's disease (PD). Transmembrane protein 175 (TMEM175) is a lysosomal cation channel whose activity is essential for lysosomal homeostasis. At present, it has been confirmed that TMEM175 is related to the pathogenesis of PD, but the relationship between the two remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>A thorough comprehension of the structure and function of TMEM175 would greatly contribute to elucidating the achievement of this objective. In this paper, the structure, composition, and function of TMEM175 and its relationship with PD will be reviewed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057436","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 Insights Into Cellular Response in Abdominal Aortic Occlusion-Induced Hippocampal Injury","authors":"Changhong Ren,&nbsp;Ling Kui,&nbsp;Jun Xu,&nbsp;Fang Tong,&nbsp;Xiaojie Wang,&nbsp;Jianping Ma,&nbsp;Xiaomei Tian,&nbsp;Guoyun Wang,&nbsp;Feng-Yong Liu,&nbsp;Sijie Li,&nbsp;Xunming Ji","doi":"10.1111/cns.70154","DOIUrl":"10.1111/cns.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Ischemia–reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type–specific molecular pathology in the hippocampus after ischemia is poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In this study, we adopted a mouse AAO to investigate the single-cell transcriptome in the hippocampi in AAO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6 mice (8 weeks old) were used to create an AAO model, with animals divided into Sham and I/R groups. The I/R group was subjected to 2 h of ischemia followed by 24 h of reperfusion, after which hippocampal tissues were collected for single-cell RNA sequencing and histological analysis. Behavioral tests, including the Rotarod, Y-maze, and new object recognition tests, were performed daily for 28 days post-surgery to evaluate neurological function. A total of 62,624 cells were corresponding 7 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in AAO mice and the function of these cell-specific Genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AAO injury upregulated astrocyte and oligodendrocyte precursor cell (OPC) proportions (<i>p</i>-value &lt; 0.05). Astrocytes showed unique gene expression related to neurogenesis and mRNA processing. Five distinct astrocyte subtypes emerged post-injury. OPCs exhibited enhanced synapse organization. Microglia activation and the elevated expression level of the epithelial cell oxidative phosphorylation protein–protein interaction (PPI) module indicate an inflammatory response and metabolic changes in response to AAO injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our scRNA-seq analysis provides insights into transcriptional changes at the single-cell level in response to AAO-induced hippocampal injury. This study illustrates how the hippocampal region responds to such injury and identifies potential therapeutic targets for intervention, thereby paving the way for future research and treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996371","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":"ADAR1 Promotes the Progression and Temozolomide Resistance of Glioma Through p62-Mediated Selective Autophagy","authors":"Yuyan Zhang,&nbsp;Huiling Guo,&nbsp;Jiahao Bu,&nbsp;Weiwei Wang,&nbsp;Li Wang,&nbsp;Zhibo Liu,&nbsp;Yuning Qiu,&nbsp;Qimeng Wang,&nbsp;Lijuan Zhou,&nbsp;Xianzhi Liu,&nbsp;Liwei Ma,&nbsp;Jianwei Wei","doi":"10.1111/cns.70168","DOIUrl":"10.1111/cns.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Resistance to temozolomide (TMZ) remains is an important cause of treatment failure in patients with glioblastoma multiforme (GBM). ADAR1, as a member of the ADAR family, plays an important role in cancer progression and chemotherapy resistance. However, the mechanism by which ADAR1 regulates GBM progression and TMZ resistance is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We first constructed stable transfected strains in which ADAR1 was knocked down and overexpressed to investigate the effect of ADAR1 on the first-line glioma chemotherapy drug TMZ. Subsequently, we validated that ADAR1 induces autophagy activation and used autophagy inhibitors to suppress autophagy, demonstrating that ADAR1 enhances TMZ resistance through autophagy. We further knocked down p62 (SQSTM1) based on the overexpression of ADAR1, and the results showed that ADAR1 regulates selective autophagy through the p62 regulation. Finally, we demonstrated through mutations at both edited and nonedited sites that ADAR1 regulates selective autophagy in an edited dependent way.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Further analysis showed that in the presence of TMZ, elevated ADAR1 promoted TMZ induced autophagy activation. Further research revealed that ADAR1 enhances TMZ resistance through p62-mediated selective autophagy. Further, ADAR1 regulates selective autophagy in an edited dependent way. Our results indicate a relationship between ADAR1 levels and the response of glioma patients to TMZ treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found that the expression of ADAR1 is upregulated in GBM and is associated with tumor grade and TMZ resistance. Elevated expression of ADAR1 predicts poor prognosis in GBM patients and promotes tumor growth in vivo or in vitro.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997018","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":"CHOP-Mediated Disruption of Hippocampal Synaptic Plasticity and Neuronal Activity Contributes to Chronic Pain-Related Cognitive Deficits","authors":"Qingsheng Meng,&nbsp;Songxue Su,&nbsp;Lei Lei,&nbsp;Yubing Zhang,&nbsp;Jiabin Duan,&nbsp;Xiuhua Ren,&nbsp;Yihang Song,&nbsp;Xiaoyu Hu,&nbsp;Shiyue Chen,&nbsp;Weidong Zang,&nbsp;Zhen Zhang,&nbsp;Jing Cao","doi":"10.1111/cns.70160","DOIUrl":"10.1111/cns.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Endoplasmic reticulum (ER) stress-induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify the unique role played by C/EBP homologous protein (CHOP) as a biomarker of the unfolded protein response (UPR) in the etiology of chronic pain and related cognitive impairments following chronic constrictive nerve injury (CCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The memory capability following CCI was assessed utilizing the Morris water maze (MWM) and fear conditioning test (FCT). Activation of the UPR was quantified by assessing levels of CHOP and key ER stress sensors. The terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay and the levels of cleaved caspase-3 were utilized to assess apoptosis level. Synaptic plasticity was assessed via a modified Golgi-Cox staining method, and long-term potentiation (LTP) measurements were taken. Neuronal activity was determined by immunofluorescence and fiber photometry. Knockdown of CHOP and alleviation of ER stress were selectively induced by LV-Ddit3-shRNAs and the chemical chaperone 4-phenylbutyric acid (4-PBA), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice subjected to CCI displayed enduring pain and cognitive impairments evident on Days 21–28 post-surgery. Following CCI, changes in the dorsal CA1 (dCA1) manifested as ER dilation, upregulation of CHOP and upstream signaling molecules, reduced dendritic spine density, and PSD95 levels, and impaired LTP. Additionally, the co-localization of CaMKIIα/c-Fos and CaMKIIα^dCA1-mediated calcium signaling was significantly reduced, while the activation of CaMKIIα was found to mitigate cognitive impairments in CCI mice. Selective knockdown of CHOP enhanced synaptic plasticity and CaMKIIα neuron activity, while 4-PBA treatment alleviated ER stress, synergistically improving cognitive deficits associated with chronic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CCI-induced CHOP upregulation impairs dCA1 synaptic plasticity and neuronal activity, leading to chronic pain-related cognitive deficits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997019","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":"Is Overlain Display a Right Choice for AR Navigation? A Qualitative Study of Head-Mounted Augmented Reality Surgical Navigation on Accuracy for Large-Scale Clinical Deployment","authors":"Jian Ye,&nbsp;Qingwen Chen,&nbsp;Tao Zhong,&nbsp;Jian Liu,&nbsp;Han Gao","doi":"10.1111/cns.70217","DOIUrl":"10.1111/cns.70217","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>During the course of the past two decades, head-mounted augmented reality surgical navigation (HMARSN) systems have been increasingly employed in a variety of surgical specialties as a result of both advancements in augmented reality–related technologies and surgeons' desires to overcome some drawbacks inherent to conventional surgical navigation systems. In the present time, most experimental HMARSN systems adopt overlain display (OD) that overlay virtual models and planned routes of surgical tools on corresponding physical tissues, organs, lesions, and so forth, in a surgical field so as to provide surgeons with an intuitive and direct view to gain better hand–eye coordination as well as avoid attention shift and loss of sight (LOS), among other benefits during procedures. Yet, its system accuracy, which is the most crucial performance indicator of any surgical navigation system, is difficult to ascertain because it is highly subjective and user-dependent. Therefore, the aim of this study was to review presently available experimental OD HMARSN systems qualitatively, explore how their system accuracy is affected by overlain display, and find out if such systems are suited to large-scale clinical deployment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We searched PubMed and ScienceDirect with the following terms: head mounted augmented reality surgical navigation, and 445 records were returned in total. After screening and eligibility assessment, 60 papers were finally analyzed. Specifically, we focused on how their accuracies were defined and measured, as well as whether such accuracies are stable in clinical practice and competitive with corresponding commercially available systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>The primary findings are that the system accuracy of OD HMARSN systems is seriously affected by a transformation between the spaces of the user's eyes and the surgical field, because measurement of the transformation is heavily individualized and user-dependent. Additionally, the transformation itself is potentially subject to changes during surgical procedures, and hence unstable. Therefore, OD HMARSN systems are not suitable for large-scale clinical deployment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996955","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":"A Risk Model Based on Ferroptosis-Related Genes OSMR, G0S2, IGFBP6, IGHG2, and FMOD Predicts Prognosis in Glioblastoma Multiforme","authors":"Yaqiu Wu,&nbsp;Ling Liu,&nbsp;Zhili Li,&nbsp;Tian Zhang,&nbsp;Qi Wang,&nbsp;Meixiong Cheng","doi":"10.1111/cns.70161","DOIUrl":"10.1111/cns.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma multiforme (GBM) is a common and highly aggressive brain tumor with a poor prognosis. However, the prognostic value of ferroptosis-related genes (FRGs) and their classification remains insufficiently studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to explore the significance of ferroptosis classification and its risk model in GBM using multi-omics approaches and to evaluate its potential in prognostic assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ferroptosis-related genes (FRGs) were retrieved from databases such as FerrDB. The TCGA-GBM and CGGA-GBM datasets were used as training and testing cohorts, respectively. Univariate Cox regression and LASSO regression analyses were performed to establish a risk model comprising five genes (OSMR, G0S2, IGFBP6, IGHG2, FMOD). A Meta-analysis of integrated TCGA and GTEx data was conducted to examine the differential expression of these genes between GBM and normal tissues. Key gene protein expression differences were analyzed using CPTAC and HPA databases. Single-cell RNA sequencing (scRNA-seq) analysis was employed to explore the cell type-specific distribution of these genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The five-gene risk model demonstrated significant prognostic value in GBM. Meta-analysis revealed distinct expression patterns of the identified genes between GBM and normal tissues. Protein expression analysis confirmed these differences. scRNA-seq analysis highlighted the diverse distribution of these genes across different cell types, offering insights into their biological roles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The ferroptosis-based risk model provides valuable prognostic insights into GBM and highlights potential therapeutic targets, emphasizing the biological significance of ferroptosis-related genes in tumor progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997017","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 “Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro”","authors":"","doi":"10.1111/cns.70219","DOIUrl":"10.1111/cns.70219","url":null,"abstract":"<p>Yao XY, Cao BE, Liu JY, Lv QK, Zhang JR, Cheng XY, Mao CJ, Ma QH, Wang F, Liu CF. “Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro”. <i>CNS Neurosci Ther</i>. 2024;30(10):e70088. doi: 10.1111/cns.70088.</p><p>The authors would like to correct Figure 2B, as errors were made during its preparation for publication. We declare that these corrections do not alter the results or conclusions of this paper. The corrected version of Figure 2, including Figure 2B, is provided here.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969001","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 Efficacy of Intensive Statin Therapy in Acute Ischemic Stroke Following Intravenous Thrombolysis: The CASE II Study","authors":"Fujian Chen,&nbsp;Huan Zhou,&nbsp;Tingxia Zhang,&nbsp;Liangxue Wang,&nbsp;Hongfang Chen,&nbsp;Jin Hu,&nbsp;Guomin Xie,&nbsp;Shenqiang Yan,&nbsp;Min Lou,&nbsp;CASE-II Investigators","doi":"10.1111/cns.70186","DOIUrl":"10.1111/cns.70186","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the efficacy of early intensive statin therapy following intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AIS patients who received IVT and statin therapy were included from multicenter registry databases. The primary endpoint was functional independence, defined by a modified Rankin Scale (mRS) score of 0–2 at 90 days. Propensity score matching (PSM) analyses were employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 21,349 patients were included in this study, with a mean age of 68.5 ± 12.6 years, of whom 13,578 (63.6%) were male. The baseline NIHSS score was 4 (IQR 2–8). A total of 9532 patients (44.6%) received intensive statin therapy. In the PSM analysis, the proportion of patients with mRS scores of 0–2 was significantly higher in the intensive statin therapy group (OR = 1.095, 95% CI 1.022–1.173, <i>p</i> = 0.010). Statin type modified the effect of intensive statin therapy on functional independence (<i>p</i>-value for interaction = 0.030). Treatment effects favoring the intensive approach were observed in patients receiving atorvastatin (OR = 1.134, 95% CI 1.051–1.224, <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Early intensive statin therapy following IVT leads to a significant but modest improvement in neurological outcomes, particularly in patients treated with atorvastatin as part of the intensive regimen.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969006","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":"C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats","authors":"Xiaoling Peng,&nbsp;Jie Ju,&nbsp;Zheng Li,&nbsp;Jie Liu,&nbsp;Xiaoqian Jia,&nbsp;Jihong Wang,&nbsp;Jihao Ren,&nbsp;Feng Gao","doi":"10.1111/cns.70216","DOIUrl":"10.1111/cns.70216","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sprague-Dawley rats were intrathecally treated with morphine twice daily for 9 days to establish morphine-tolerant rat model. Tail-flick latency test was performed to identify the analgesic effect of morphine. The role of microglia, astrocyte and C3-C3aR axis in morphine tolerance were elucidated by real-time quantitative polymerase chain reaction, Western blot, and immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic morphine treatment notably promoted the activation of microglia, upregulated the production of proinflammatory mediators (interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q)). Simultaneously, it programed astrocytes to a pro-inflammatory phenotype (A1), which mainly expresses complement 3 (C3) and serping1. PLX3397 (a colony-stimulating factor 1 receptor (CSF1R) inhibitor), Compstain (a C3 inhibitor) and SB290157(a C3aR antagonist) could reverse the above pathological process and alleviate morphine tolerance to different extents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings identify C3-C3aR axis as an amplifier of microglia-astrocyte crosstalk, neuroinflammation and a node for therapeutic intervention in morphine tolerance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055764","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":"Olfactory Network Disruptions as Mediators of Cognitive Impairment in De Novo Parkinson's Disease","authors":"Yi Xing,&nbsp;Hao Zhou,&nbsp;Shuoying Chen,&nbsp;Yajie Wang,&nbsp;Jingru Ren,&nbsp;Yiting Cao,&nbsp;Jingzhe Li,&nbsp;Weiguo Liu","doi":"10.1111/cns.70198","DOIUrl":"10.1111/cns.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is characterized by olfactory dysfunction (OD) and cognitive deficits at its early stages, yet the link between OD and cognitive deficits is also not well-understood. This study aims to examine the changes in the olfactory network associated with OD and their relationship with cognitive function in de novo PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 116 drug-naïve PD patients and 51 healthy controls (HCs) were recruited for this study. Graph theoretical approaches were employed to reveal the abnormalities of topological characteristics in the olfactory network. Network-based statistics (NBS) analysis was employed to identify the abnormal subnetworks within the olfactory network. Moreover, partial correlation analysis and mediation analysis were performed to examine the relationship between the abnormal network metrics, olfactory function, and cognitive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Graph theoretical approaches revealed reduced betweenness centrality of the left insula in PD patients with OD. NBS analysis identified a disrupted subnetwork with decreased functional connectivity, primarily involving limbic regions. The average functional connectivity of this subnetwork partially mediated the relationship between olfactory and cognitive performance. Higher-granularity network analysis further highlighted the insula's key role and revealed reduced efficiency of information integration within the olfactory network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>OD was associated with specific changes in the functional olfactory network, which, in turn, affects cognitive function. These findings underscore the importance of assessing and addressing OD. Understanding the neural correlates of OD could provide novel insights into the management and comprehension of cognitive impairment in PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969003","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}