CNS Neuroscience & Therapeutics最新文献

{"title":"A Study of Sex Differences in the Biological Pathways of Stress Regulation in Mice","authors":"Yajun Qiao,&nbsp;Hanxi Chen,&nbsp;Juan Guo,&nbsp;Xingfang Zhang,&nbsp;Xinxin Liang,&nbsp;Lixin Wei,&nbsp;Qiannan Wang,&nbsp;Hongtao Bi,&nbsp;Tingting Gao","doi":"10.1111/cns.70433","DOIUrl":"https://doi.org/10.1111/cns.70433","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stress is closely related to life, and it can also cause many mental disorders. However, there are significant sex differences in neuropsychiatric disorders associated with stress, particularly in depression, where the lifetime risk of depression in women is approximately twice that of men. However, the specific mechanism of this process has not been explained in detail.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Chronic restraint stress (CRS) + chronic and unpredictable mild stress (CUMS) was used to simulate social stress, and behavioral experiments, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, and metabolomics analysis of hippocampal and intestinal contents were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that stress induced anxiety-like behavior in female mice and depression-like behavior in male mice. Sex differences in behavior may be related to monoamine neurotransmitters, hyperactivity of HPA axis, inflammatory factors, gut microbiota, and brain–gut metabolism. It is worth noting that stress caused opposite trends in DA (dopamine) levels, abundance of f-lactobaciliaceae, and levels of metabolites (1, 2-distearoyl-SN-glycero-3-phosphocholine) and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z)) in male and female mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The difference in neurotransmitter levels, the disorder of gut microbiota, and the abnormal brain and gut metabolism may lead to the gender difference in stress behavior.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944796","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":"Hydrogen Sulfide Modulates Microglial Polarization and Remodels the Injury Microenvironment to Promote Functional Recovery After Spinal Cord Injury","authors":"Yu Wang,&nbsp;Xinyi Jia,&nbsp;Yuqi Zhang,&nbsp;Haibin Shi,&nbsp;Yuhui Sun,&nbsp;Yaobo Liu","doi":"10.1111/cns.70431","DOIUrl":"https://doi.org/10.1111/cns.70431","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) disrupts tissue homeostasis, leading to persistent neuroinflammation and scar formation that severely impedes functional recovery. Current therapeutic approaches are insufficient to address these challenges. In this study, we investigated whether exogenous hydrogen sulfide (H₂S) can modulate neuroinflammatory responses and remodel the injury microenvironment to promote tissue repair and restore motor function following SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T10 crush SCI was induced in mice, followed by daily intraperitoneal administration of the H₂S donor anethole trithione (ADT). Immunofluorescence staining, tissue clearing, western blotting, and behavioral assessments were performed to evaluate scar formation, vascular regeneration, neuronal survival, and motor function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ADT-based H₂S therapy significantly promoted wound healing, inhibited scar formation, enhanced vascular regeneration, and protected residual neurons and axons from secondary injury. Mechanistically, H₂S suppressed microglial proliferation and activation, promoting their polarization toward an anti-inflammatory phenotype and alleviating neuroinflammation. Consequently, motor function recovery was markedly improved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>H₂S modulates microglial activation and mitigates neuroinflammation, establishing a permissive microenvironment for SCI repair and significantly enhancing motor function recovery. Given ADT's established clinical safety and its effective gasotransmitter properties, our findings underscore its immediate translational potential for treating SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944578","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":"Unraveling the Interplay Between Metabolism and Neurodevelopment in Health and Disease","authors":"Yanqing He,&nbsp;Kang Xie,&nbsp;Kang Yang,&nbsp;Nianhua Wang,&nbsp;Longbo Zhang","doi":"10.1111/cns.70427","DOIUrl":"https://doi.org/10.1111/cns.70427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurodevelopment is a multifaceted and tightly regulated process essential for the formation, maturation, and functional specialization of the nervous system. It spans critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, which collectively establish the foundation for cognitive, behavioral, and emotional functions. Metabolism serves as a cornerstone for neurodevelopment, providing the energy and substrates necessary for biosynthesis, signaling, and cellular activities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Key metabolic pathways, including glycolysis, lipid metabolism, and amino acid metabolism, support processes such as cell proliferation, myelination, and neurotransmitter synthesis. Crucial signaling pathways, such as insulin, mTOR, and AMPK, further regulate neuronal growth, synaptic plasticity, and energy homeostasis. Dysregulation of these metabolic processes is linked to a spectrum of neurodevelopmental disorders, including autism spectrum disorders (ASDs), intellectual disabilities, and epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review investigates the intricate interplay between metabolic processes and neurodevelopment, elucidating the molecular mechanisms that govern brain development and the pathogenesis of neurodevelopmental disorders. Additionally, it highlights potential avenues for the development of innovative strategies aimed at enhancing brain health and function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944795","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":"Oral 7,8-Dihydroxyflavone Protects Retinal Ganglion Cells by Modulating the Gut-Retina Axis and Inhibiting Ferroptosis via the Indoleacrylic Acid-AhR-ALDH1A3-FSP1 Pathway","authors":"Yanping Zhou,&nbsp;Yifan Feng,&nbsp;Yingxi Zhao,&nbsp;Yu Wu,&nbsp;Min Li,&nbsp;Xi Yang,&nbsp;Xinyuan Wu,&nbsp;Xiangwu Chen","doi":"10.1111/cns.70442","DOIUrl":"https://doi.org/10.1111/cns.70442","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>7,8-Dihydroxyflavone (7,8-DHF) activates the TrkB receptor, offering neuroprotection, yet its pharmacological limitations restrict its safe and effective delivery to the eye and brain, impeding clinical translation. This study explores the protective effects of oral 7,8-DHF on retinal ganglion cells (RGCs) by inhibiting ferroptosis and investigates the involvement of the gut-retina axis, particularly the Indoleacrylic acid (IDA)-AhR-ALDH1A3-FSP1 pathway, with potential clinical implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To evaluate the neuroprotective effects of oral 7,8-DHF, retinal 3D cultures were used for axon regeneration and GCL cell apoptosis, and ONC models for RGC survival and electrophysiology. Mechanisms were investigated by assessing ferroptosis-related proteins via Western blotting, screening differential metabolites in PC12 cells, analyzing mitochondrial changes with TEM, evaluating gut microbiota shifts, and examining metabolite changes in retina and feces.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Oral 7,8-DHF enhanced RGC survival and retinal function in the ONC model by inhibiting ferroptosis, independent of TrkB activation. This effect was blocked by antibiotics and AHR, ALDH1A3, and FSP1 inhibitors. Metabolomics showed increased IDA in retina and feces, with IDA inhibiting ferroptosis in PC12 cells and promoting axonal regeneration in retinal explants. Western blot revealed upregulation of nAhR and ALDH1A3, while non-FSP1 ferroptosis proteins were unaffected. 7,8-DHF also altered gut microbiota, increasing Parasutterella, which correlated with higher IDA levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>7,8-DHF regulates the gut microbiota to increase IDA levels in the intestine, which subsequently leads to the accumulation of IDA in the retina. This activates the AhR-ALDH1A3-FSP1 axis in the retina, thereby inhibiting retinal ferroptosis and exerting neuroprotective effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944857","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":"Lipocalin 2 Facilitates the Initial Compromise of the Blood–Brain Barrier Integrity in Chronic Cerebral Hypoperfusion","authors":"Qianqian Nie,&nbsp;Liren Zhang,&nbsp;Zhengsheng Gu,&nbsp;Yuchao Li,&nbsp;Xiaoying Bi","doi":"10.1111/cns.70438","DOIUrl":"https://doi.org/10.1111/cns.70438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Vascular cognitive impairment (VCI) is primarily attributed to vascular risk factors and cerebrovascular disease. Chronic cerebral hypoperfusion (CCH) initiates in the early stages of VCI and contributes to blood–brain barrier (BBB) disruption. Nevertheless, the precise molecular mechanisms underlying this process remain elusive and warrant further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Bilateral Carotid Artery Stenosis (BCAS) model was employed to simulate CCH, and the permeability of the BBB in the mouse frontal cortex was assessed at various time points post-operation. Transcriptome sequencing was conducted to identify differentially expressed genes (DEGs), which were then intersected with cortical gene chip data from human vascular dementia cases. Key genes identified through this analysis were subsequently measured in the serum of VCI patients and correlated with cognitive performance scores. Additionally, in vivo experiments were conducted to validate the influence of these key genes on BBB endothelial-mesenchymal transition (EndMT) and peripheral neutrophil infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Time-course studies investigating BBB disruption revealed an increase in BBB permeability in the frontal cortex of mice on day 14 following BCAS, a stage at which the mice had not yet exhibited cognitive impairment. Subsequent sequencing analyses, integrated with human cortical gene expression profiles, identified Lipocalin 2 (LCN2) as a pivotal gene involved in mediating inflammatory responses and cell migration. Clinical studies have demonstrated that LCN2 is upregulated in the serum of patients with VCI and exhibits a significant negative correlation with Montreal Cognitive Assessment (MOCA) scores. Downregulation of LCN2 leads to a reduction in EndMT markers and peripheral neutrophil infiltration, as well as significant enhancements in learning and memory in BCAS mice through modulation of the MEK/ERK signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study elucidates the temporal characteristics and key molecular mechanisms underlying BBB disruption in the frontal cortex during CCH, thereby identifying novel potential targets for the early diagnosis and treatment of VCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944859","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 Variation of White Matter Connectome After Surgery Revealed Factors Affecting Supplementary Syndrome Recovery Time in Low-Grade Glioma Patients","authors":"Shengyu Fang,&nbsp;Yuzhe Li,&nbsp;Shimeng Weng,&nbsp;Jiahan Dong,&nbsp;Jiangwei Wang,&nbsp;Zhong Zhang,&nbsp;Xing Fan,&nbsp;Yinyan Wang,&nbsp;Wenbin Ma,&nbsp;Tao Jiang","doi":"10.1111/cns.70426","DOIUrl":"https://doi.org/10.1111/cns.70426","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Supplementary motor area (SMA) syndrome is a common complication after SMA glioma resection. The compensatory mechanism of the structural sensorimotor network (SMN) and the factors influencing the recovery time of SMA syndrome have not been 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;Pre- and postoperative diffusion tensor images of 42 low-grade glioma patients with SMA syndrome were processed to construct white matter connectomes. Patients were classified into fast and slow-recovery groups according to whether postoperative motor disorder recovers within 7 days. Fiber counts between nodes and graph theory topological properties were calculated. The shortest distance from the surgical region to the corticospinal tract (&lt;i&gt;d&lt;/i&gt;&lt;sub&gt;CST&lt;/sub&gt;) and the upper limb region of Brodmann area 4 (A4ul) was measured to find correlations with recovery time. Cox regressions were conducted to identify factors associated with SMA syndrome recovery time. A general linear model was formed using significant factors in multivariate Cox analysis to predict recovery time.&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;Decrease of fiber number between lesioned-hemispheric A4ul and contralateral SMN is correlated with prolongation of recovery time. Compared with the slow-recovery group, a higher increase of nodal degree centrality and nodal efficiency of ipsilateral A4ul was found in the fast-recovery group (nodal efficiency: left pre-op: 0.182 ± 0.009, left post-op: 0.231 ± 0.008, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; right pre-op: 0.157 ± 0.021, right post-op: 0.195 ± 0.018, &lt;i&gt;p&lt;/i&gt; = 0.0011); (nodal degree centrality: left pre-op: 1.985 ± 0.166; left post-op: 3.195 ± 0.230, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001; right pre-op: 1.620 ± 0.389; right post-op: 2.411 ± 0.452, &lt;i&gt;p&lt;/i&gt; = 0.0005). Multivariate Cox analysis indicated that the increase in nodal efficiency of A4ul and &lt;i&gt;d&lt;/i&gt;&lt;sub&gt;CST&lt;/sub&gt; were protective factors for SMA syndrome recovery time. A significant negative correlation between the predict score and recovery time was found in the left lesion group (&lt;i&gt;r&lt;/i&gt; = −0.756, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001), and the same trend was found in the right lesion group (&lt;i&gt;r&lt;/i&gt; = −0.531, &lt;i&gt;p&lt;/i&gt; = 0.076).&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;This study revealed an increase in lesioned-hemispheric A4ul nodal efficiency and long &lt;i&gt;d&lt;/i&gt;&lt;sub&gt;CST&lt;/sub&gt; as protective factors in SMA syndrome recovery. A decrease in the number of interhemispheric fibers connecting lesioned-hemispheric A4ul to nodes on the contralateral hemisphere was correlated w","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930495","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":"Xenon in ALS Treatment: What Are We Waiting for?","authors":"Ferhat Çelik","doi":"10.1111/cns.70435","DOIUrl":"https://doi.org/10.1111/cns.70435","url":null,"abstract":"&lt;p&gt;Glutamate, the most abundant neurotransmitter in the central nervous system (CNS), is the key regulator of neuronal excitability. It is well established that glutamate exerts its effects through three main ionotropic receptors—N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors—to maintain synaptic balance and drive neurotransmission [&lt;span&gt;1&lt;/span&gt;]. NMDA receptors (NMDARs) are particularly notable for their high permeability to Ca&lt;sup&gt;2+&lt;/sup&gt; ions, a property that, when combined with intracellular calcium overload, endoplasmic reticulum stress, and mitochondrial dysfunction, can trigger excitotoxicity mechanisms [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Dysfunctions in the glutamatergic system have long been investigated in relation to neurodegenerative diseases, particularly in the context of Amyotrophic Lateral Sclerosis (ALS). Analyses of spinal cord and cortical tissues from ALS patients have revealed significant reductions in the function of glutamate transporter proteins [&lt;span&gt;3&lt;/span&gt;]. Similarly, postmortem studies have reported impairments in glutamate metabolism. Moreover, mutations associated with ALS, such as SOD1, C9ORF72, TARDBP, and FUS, have been shown to have a direct connection to dysregulation within the glutamatergic system [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Xenon (Xe), which has been used as a safe anesthetic agent since the mid-20th century, has also garnered attention for its neuroprotective properties over the past two decades. The first study demonstrating Xenon's neuroprotective effects was published in 2003, using rat models of ischemic brain injury [&lt;span&gt;5&lt;/span&gt;]. Subsequent research has shown that Xenon preserves neurocognitive functions and reduces neuronal loss in conditions such as focal ischemia and perinatal hypoxic–ischemic injury [&lt;span&gt;6, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;One of the key mechanisms underlying Xenon's anesthetic and neuroprotective effects is its antagonistic action on NMDA receptors [&lt;span&gt;8&lt;/span&gt;]. NMDA receptor inhibition may serve as a protective mechanism against glutamate excitotoxicity in diseases such as ALS. Xenon's ability to easily cross the blood–brain barrier and rapidly enter and exit brain cells makes it pharmacologically advantageous [&lt;span&gt;9&lt;/span&gt;]. In addition to NMDA antagonism, it has also been reported to inhibit AMPA and kainate receptors; however, the significance of these effects in the context of ALS remains unclear [&lt;span&gt;9&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Xenon's potential neuroprotective effects in ALS are not limited to NMDA receptor antagonism. There is evidence suggesting that it may also influence key pathophysiological mechanisms of ALS, including apoptotic cell death, oxidative stress, and microglial dysfunction [&lt;span&gt;10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Given all these findings, it is evident that Xenon should be investigated as a potential therapeutic agent for ALS. However, despite its promising mechanisms, there are currently no clinical or preclinical studies directly","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930496","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":"Multiomic Underpinnings of Drug Targets for Intracranial Aneurysm: Evidence From Diversified Mendelian Randomization","authors":"Yu-Xiang Fan,&nbsp;Di Lu,&nbsp;Cheng-Bin Yang,&nbsp;Zi-Hao Song,&nbsp;Yi-Guang Chen,&nbsp;Yong-Jie Ma,&nbsp;Jing-Wei Li,&nbsp;Hong-Qi Zhang","doi":"10.1111/cns.70430","DOIUrl":"https://doi.org/10.1111/cns.70430","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The absence of pharmaceutics poses challenges in preventing intracranial aneurysm (IA) progression and rupture. This research emphasized identifying drug targets for IA through a druggable genome-wide Mendelian randomization (MR) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample MR analysis was performed leveraging <i>cis-</i>expression quantitative trait loci in the blood (<i>n</i> = 31,684) and arteries (<i>n</i> = 584) aligned with 5883 druggable genes as exposure and the largest IA summary statistics (<i>n</i> = 7495) as outcome. Bayesian colocalization analysis, plasma cis-protein quantitative trait loci (<i>n</i> = 35,559), and external IA cohorts (FinnGen, <i>n</i> = 2582; Zhou, <i>n</i> = 380) were used for validation. A phenome-wide MR (Phe-MR) incorporating 783 diseases uncovered side effects. Multivariable MR addressed unmeasured pleiotropy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five druggable genes in blood and one in the coronary artery showed significant association with IA risk (<i>p-</i>_<i>FDR</i> ≤ 0.05). <i>NT5C2</i>, <i>PRCP</i>, and <i>CRMP1</i> shared a common variant with IA (PPH4 ≥ 0.8). The external validation cohorts confirmed the effects of <i>NT5C2</i> on IA (FinnGen cohort, Odds Ratio [OR], 0.81, 95% Confidential Interval [95% CI] 95% CI, 0.707–0.930; <i>p</i> = 0.003; Zhou cohort, OR, 0.68, 95% CI, 0.469–0.983; <i>p</i> = 0.041). The genetically predicted protein level of <i>PRCP</i> validated an inverse association with IA risk (OR, 0.734; 95% CI, 0.561–0.959; <i>p =</i> 0.023). The Phe-MR revealed insignificance for <i>NT5C2</i> or <i>PRCP</i>. Direct causal effects on IA were 0.60 (95% CI, 0.457–0.797; <i>p</i> = 1.36E-05) for <i>PRCP</i> and 0.67 (95% CI, 0.527–0.860; <i>p</i> = 0.002) for <i>NT5C2</i> after adjusting for IA modifiable risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>NT5C2</i> and <i>PRCP</i> were identified as potential drug targets for IA, with effects independent of known modifiable risk factors. Targeting <i>NT5C2</i> and <i>PRCP</i> appeared exclusively effective and safe.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930497","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":"ND-AMD: A Web-Based Database for Animal Models of Neurological Disease With Analysis Tools","authors":"Yue Wu,&nbsp;Lu Li,&nbsp;Yi-Tong Li,&nbsp;Lei Zhang,&nbsp;Shuang Gong,&nbsp;Yang Zhang,&nbsp;Jue Wang,&nbsp;Ling Zhang,&nbsp;Qi Kong","doi":"10.1111/cns.70411","DOIUrl":"https://doi.org/10.1111/cns.70411","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;Research on animal models of neurological diseases has primarily focused on understanding pathogenic mechanisms, advacing diagnostic strateggies, developing pharmacotherapies, and exploring preventive interventions. To facilitate comprehensive and systematic studies in this filed, we have developed the &lt;i&gt;Neurological Disease Animal Model Database&lt;/i&gt; (ND-AMD), accessible at https://www.uc-med.net/NDAMD. This database is signed around the central theme of “Big Data - Neurological Diseases - Animal Models - Mechanism Research,” integrating large-scale, multi-dimensional, and multi-scale data to facilitate in-depth analyses. ND-AMD serves as a resource for panoramic studies, enabling comparative and mechanistic research across diverse experimental conditions, species, and disease models.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data were systematically retrieved from PubMed, Web of Science, and other relevant databases using Boolean search strategies with standardized MeSH terms and keywords. The collected data were curated and integrated into a structured SQL-based framework, ensuring consistency through automated validation checks and manual verification. Heterogeneity and sensitivity analyses were conducted using Cochran's Q test and the &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; statistic to assess variability across studies. Statistical workflows were implemented in Python (SciPy, Pandas, NumPy) to support multi-scale data integration, trend analysis, and model validation. Additionally, a text co-occurrence network analysis was performed using Natural Language Processing (TF-IDF and word embeddings) to identify key conceptual linkages and semantic structures across studies.&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;ND-AMD integrates data from 483 animal models of neurological diseases, covering eight disease categories, 21 specific diseases, 13 species, and 152 strains. The database provides a comprehensive repository of experimental and phenotypic data, covering behavioral, physiological, biochemical, molecular pathology, immunological, and imaging characteristics. Additionally, it incorporates application-oriented data, such as drug evaluation outcomes. To enhance data accessibility and facilitate in-depth analysis, ND-AMD features three custom-developed online tools: &lt;i&gt;Model Frequency Analysis, Comparative Phenotypic Analysis, and Bibliometric Analysis,&lt;/i&gt; enabling systematic comparison and trend identification across models and experimental conditions.&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;The centrali","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926162","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":"Neurogrit Gold Attenuates 6-OHDA-Induced Dopaminergic Neurodegeneration in Parkinson's Model of Caenorhabditis elegans by Reducing α-Synuclein Accumulation and Pink/Pdr-1 Driven Mitochondrial Dysfunction","authors":"Acharya Balkrishna,&nbsp;Nishit Pathak,&nbsp;Rani Singh,&nbsp;Vivek Gohel,&nbsp;Yash Varshney,&nbsp;Rishabh Dev,&nbsp;Anurag Varshney","doi":"10.1111/cns.70401","DOIUrl":"https://doi.org/10.1111/cns.70401","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a neurodegenerative disorder majorly associated with movement and behavioral disturbances. Pathologically, the loss of dopaminergic (DA) neurons triggered by the deposition of α-synuclein (SNCA) leads to the decrease in dopamine levels affecting motor and cognitive functions of the brain. Current pharmacotherapy for PD only addresses its symptoms but is not able to halt its progression. Traditional medicines are being increasingly used for the treatment of neurodegenerative disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The present study investigated the effects of Neurogrit Gold (NG), a herbo-mineral prescription medicine, on a Parkinson's model of <i>Caenorhabditis elegans</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Chemical characterization of NG was performed on HPLC and GC–MS/MS platforms. Evaluation of NG was done in the neurotoxicant 6-OHDA-induced N2, BZ555, and NL5901 strains of <i>C. elegans</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was observed that NG treatment did not hamper the lifespan, survival, and progeny development of <i>C. elegans</i> strains. The worms treated with NG were able to resist the deleterious effects of 6-OHDA on survival, progeny development, body bends, and chemotaxis in N2 and DA neuron degeneration in BZ555 worms. In NL5901 worms, NG treatment reduced SNCA aggregation, restored lipid content, as well as improved body bends, chemotaxis, and food uptake. Gene expression studies on 6-OHDA exposed and NG-treated N2 worms suggest that the neuroprotective effects of NG stem from its ability to regulate genes involved in mitochondrial autophagy (<i>pink-1</i>, <i>pdr-1</i>); dopamine synthesis (<i>cat-2</i>); redox (<i>sod-3</i>) and protein folding homeostasis (<i>hsf-1</i>, <i>hsp-12.3</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Neurogrit Gold has robust neuroprotective effects, making it a suitable treatment option against etiologies of Parkinson's disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919597","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}