CNS Neuroscience & Therapeutics最新文献

{"title":"miR-484 in Hippocampal Astrocytes of Aged and Young Rats Targets CSF-1 to Regulate Neural Progenitor/Stem Cell Proliferation and Differentiation Into Neurons","authors":"Jiahua Qu,&nbsp;Zhichao Lu,&nbsp;Yongbo Cheng,&nbsp;Song Deng,&nbsp;Wei Shi,&nbsp;Qianqian Liu,&nbsp;Yuejuan Ling","doi":"10.1111/cns.70415","DOIUrl":"https://doi.org/10.1111/cns.70415","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Aging-related cognitive decline is closely linked to the reduced function of neural progenitor/stem cells (NPSCs), which can be influenced by the neural microenvironment, particularly astrocytes. The aim of this study was to explore how astrocytes affect NPSCs and cognitive function during aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>H₂O₂-treated astrocytes were used to mimic the aging phenotype of astrocytes. Proteomic analysis identified altered protein expression, revealing high levels of colony-stimulating factor-1 (CSF-1) in the supernatant of H₂O₂-treated astrocytes. Primary NPSCs were isolated and cultured in vitro, then stimulated with varying concentrations of recombinant CSF-1 protein to assess its effects on NPSC proliferation, differentiation, and apoptosis. Transcriptome sequencing identified miR-484 related to CSF-1 in H₂O₂-treated astrocytes, and a dual-luciferase assay verified the interaction between miR-484 and CSF-1. The impact of miR-484 overexpression on NPSC function and cognitive restoration was evaluated both in vitro and in vivo (in 20-month-old rats).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High concentration of CSF-1 inhibited the NPSC proliferation and differentiation into neurons while inducing apoptosis. Overexpression of miR-484 downregulated CSF-1 expression by binding to its 3' untranslated region, thereby promoting the NPSC proliferation and differentiation into neurons. In 20-month-old rats, miR-484 overexpression improved spatial learning and memory in the Morris water maze, increased NPSC proliferation, and reduced apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings reveal that miR-484 regulates CSF-1 to influence NPSC proliferation, differentiation into neurons, and apoptosis, consequently improving cognitive function in 20-month-old rats. This study provides a foundation for developing therapeutic strategies targeting age-related hippocampal cognitive impairments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889191","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":"Effects of the Small-Molecule ISRIB on the Rapid and Efficient Myelination of Oligodendrocytes in Human Stem Cell-Derived Cerebral Organoids in Patients With Leukoencephalopathy With Vanishing White Matter","authors":"Wei Yan,&nbsp;Jiong Deng,&nbsp;Jie Zhang,&nbsp;Kai Gao,&nbsp;Huan Yi,&nbsp;Junjiao Zhang,&nbsp;Fan Zhang,&nbsp;Jingmin Wang,&nbsp;Yuwu Jiang,&nbsp;Ye Wu","doi":"10.1111/cns.70398","DOIUrl":"https://doi.org/10.1111/cns.70398","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Leukoencephalopathy with vanishing white matter (VWM) is a rare genetic disorder caused by mutations in any one of the &lt;i&gt;EIF2B&lt;/i&gt;1–5, which encode subunits of eukaryotic translation initiation factor 2B (eIF2B). Previous studies suggested that the dysfunction of astrocytes played a central role in the pathogenic mechanism of VWM. In addition, eIF2B participates in the unfolded protein response(UPR) by coordinating the integrated stress response (ISR). Higher susceptibility to endoplasmic reticulum stress (ERS) and abnormal overactivation of the unfolded protein response (UPR) were found in VWM, which led to logical deterioration and exacerbation of cell death. There are currently no specific treatments available for VWM.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Previous studies have successfully constructed three-dimensional brain organoids that can be used to study the development of neuronal cells during brain development. In this study, we aimed to develop a more rapid and efficient brain organoid model that would produce mature astrocytes, oligodendrocytes, and myelin within 8 weeks. The small-molecule ISR inhibitor (ISRIB) is a specific eIF2B activator by inhibiting the phosphorylation of eukaryotic translation initiation factor 2 (eIF2). Thus, ISRIB is used on eIF2B mutant organoids to determine its potential as a therapeutic approach for VWM.&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;We constructed &lt;i&gt;EIF2B4&lt;/i&gt; and &lt;i&gt;EIF2B5&lt;/i&gt; mutants as well as wild-type rapid myelinating oligodendrocyte brain organoids using human induced pluripotent stem cells (iPSCs). We observed mature astrocytes, oligodendrocytes, and myelin within 8 weeks, greatly shortening the culture period. Compared with the wild type, mutant organoids displayed a smaller size and contained increased immature and dysfunctional astrocytes, oligodendrocytes, and sparse myelin. Abnormal overactivation of the UPR pathway was also present in mutant cerebral organoids. Additionally, we found that the maturation and function of these cells in mutant organoids were significantly improved after ISRIB treatment, which also inhibited hyperactivation of the unfolded protein response (UPR) signaling pathway.&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 study established a rapid myelinating oligodendrocyte brain model in VWM for the first time, providing a more effective and tractable platform for further study of this condition and other white matter diseases. Furthermore, our findings suggested that ISRIB may have potential as a cli","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884037","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 “Targeting LncRNA-Vof16: A Novel Therapeutic Strategy for Neuropathic Pain Relief”","authors":"","doi":"10.1111/cns.70418","DOIUrl":"https://doi.org/10.1111/cns.70418","url":null,"abstract":"<p>X. He, D. H. Mauki, X. Zhao, et al., “Targeting LncRNA-Vof16: A Novel Therapeutic Strategy for Neuropathic Pain Relief,” <i>CNS Neuroscience &amp; Therapeutics</i> 31, no. 2 (2025): e70241.</p><p>The “Funding” and “Acknowledgments” sections have been updated to acknowledge the valuable contribution of the National Natural Science Foundation of China (Grant No. W2433199).</p><p>We apologize for this error.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884035","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":"Nomogram for Predicting Hemorrhagic Transformation Risk in Acute Ischemic Stroke Patients With Atrial Fibrillation","authors":"Jingjuan Chen,&nbsp;Mingyi Bao,&nbsp;Chengguo Zhang,&nbsp;Dong Pan,&nbsp;Yanting Chen,&nbsp;Yongteng Xu,&nbsp;Feng Zhou,&nbsp;Yamei Tang","doi":"10.1111/cns.70402","DOIUrl":"https://doi.org/10.1111/cns.70402","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hemorrhagic transformation (HT) is a critical complication in acute ischemic stroke (AIS) patients with atrial fibrillation (AF) awaiting anticoagulation reinitiation. No reliable predictive model exists for assessing HT risk for these patients. Clinical decisions typically rely on NIHSS score and infarct size; however, other relevant risk factors remain insufficiently explored. This study aimed to develop and validate a predictive model for assessing the risk of HT in AIS patients with AF from stroke onset to anticoagulation therapy reinitiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included AIS patients with AF from two comprehensive medical centers in China. The primary outcome was HT postinfarction confirmed with CT/MRI before anticoagulation reinitiation. Significant predictors were identified via LASSO regression in the training set, followed by multivariable logistic regression for developing a predictive model and generating the nomogram. Model performance was validated in a separate external cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the training cohort (<i>n</i> = 629), 174 patients (27.7%) developed HT. LASSO logistic regression revealed that infarct size, NIHSS score, diabetes mellitus, reperfusion therapy, left ventricular ejection fraction, and prehospital antihypertensive treatment were significant HT predictors. In the external validation cohort (<i>n</i> = 236), 61 patients (25.8%) developed HT. The nomogram exhibited strong predictive performance, with AUCs of 0.720 in the training set and 0.747 in the validation set.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed nomogram offers a practical tool for predicting HT risk in AIS patients with AF before anticoagulation reinitiation, potentially supporting informed clinical decision-making, though further validation is required.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875583","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":"VDAC1 Inhibition Protects Against Noise-Induced Hearing Loss via the PINK1/Parkin Pathway","authors":"Yuchen Jin,&nbsp;Wenqi Dong,&nbsp;Yumeng Jiang,&nbsp;Lingkang Dong,&nbsp;Zhuangzhuang Li,&nbsp;Dongzhen Yu","doi":"10.1111/cns.70410","DOIUrl":"https://doi.org/10.1111/cns.70410","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study examined the effect of 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), an anion channel blocker of voltage-dependent anion channel 1 (VDAC1), on noise-induced hearing loss (NIHL) and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cochlear explants and House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were used to assess the effect of DIDS in vitro. Auditory brainstem responses were used to assess auditory functions in mice. Immunofluorescence staining of myosin 7a and CTBP2 were used to examine hair cells and synaptic ribbons. The accumulation of reactive oxygen species (ROS) was measured by 4-HNE staining. The gene expression changes of cochlea were analyzed using RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DIDS reduced the levels of ROS in cochlear explants and attenuated cell death caused by hydrogen peroxide in both cochlear explants and HEI-OC1 cells. In C57BL/6 mice, DIDS reduced ROS generation and tumor necrosis factor-α induced by noise exposure, thereby protecting outer hair cells and inner hair cell synaptic ribbons from noise-induced damage through a mechanism involving the PINK1/Parkin signaling pathway. The preventive effect of DIDS in cochlear explants was eliminated by mitophagy inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>VDAC1 inhibition enhances mitophagy in cochlear hair cells, playing a critical role in defending against oxidative stress and inflammation. Downregulation of VDAC1 may thus be considered a therapeutic strategy for preventing cochlear hair cell damage and reducing NIHL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875554","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":"Aging-Induced Episodic-Like Memory Impairment Could be Alleviated by Melatonin Treatment via Preserving Blood–Brain Barrier Integrity and Upregulating CRTC1","authors":"Yanping Wang,&nbsp;Xinyu Zhang,&nbsp;Hui Guo,&nbsp;Shuxia Qian,&nbsp;Hailun Fang,&nbsp;Xiaoqiang Wu,&nbsp;Yufei Shen,&nbsp;Congying Xu,&nbsp;Beiqun Zhou,&nbsp;Chun Guo,&nbsp;Xudong Lu,&nbsp;Xiaoling Zhang,&nbsp;Xinchun Jin","doi":"10.1111/cns.70412","DOIUrl":"https://doi.org/10.1111/cns.70412","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aging is accompanied by impairments in stimulus recognition, and decreased melatonin levels have been shown in aged mice and humans. These age-related changes are associated with an increased risk of neurological diseases. In the present study, our aim is to investigate whether melatonin supplementation could ameliorate age-related cognitive decline in aged mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were treated with melatonin or saline. The novel object recognition (NOR) task was used to provide a simultaneous assessment of object and object location memory, which is a component of episodic-like memory. Blood–brain barrier (BBB) leakage was assessed using an Immunoglobulin G (IgG) leakage assay. Immunofluorescence and Western blot analyses were employed to investigate changes in protein levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that aging impairs memory in the NOR task, with concomitant decreases in the levels of synaptophysin (SYP), CREB-regulated transcription coactivator 1 (CRTC1), and phosphorylated AMP-activated protein kinase (p-AMPK) levels within the prefrontal cortex (PFC) and hippocampus. Moreover, alongside compromised BBB integrity, aging results in the degradation of occludin in both the PFC and hippocampus. Our findings demonstrate that aging impairs memory performance in the NOR task, accompanied by reductions in SYP, CRTC1, and p-AMPK levels within the PFC and hippocampus. Furthermore, alongside compromised BBB integrity, aging results in the degradation of occludin in both the PFC and hippocampus. More importantly, PDZ and LIM domain 5 (Pldim5) was upregulated in melatonin-treated mice, and aging-related memory impairment in the NOR task was significantly reduced in Pdlim5^−/− mice. Notably, 1 week of melatonin (10 mg/kg) treatment significantly improved memory, along with enhanced BBB integrity, Pdlim5 downregulation, and CRTC1 and p-AMPK upregulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, our findings suggest that melatonin ameliorates aging-related memory decline in the NOR task by downregulating Pdlim5, maintaining BBB integrity, and upregulating CRTC1 and p-AMPK in aged mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875611","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":"Balancing Anti-Inflammation and Neurorepair: The Role of Mineralocorticoid Receptor in Regulating Microglial Phenotype Switching After Traumatic Brain Injury","authors":"Bin Zhang,&nbsp;Miao Bai,&nbsp;Mengshi Yang,&nbsp;Yumei Wang,&nbsp;Xueling Zhang,&nbsp;Xiyu Chen,&nbsp;Min Gao,&nbsp;Baiyun Liu,&nbsp;Guangzhi Shi","doi":"10.1111/cns.70404","DOIUrl":"https://doi.org/10.1111/cns.70404","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As potent anti-inflammatory agents, glucocorticoids (GCs) have been widely used in the treatment of traumatic brain injury (TBI). However, their use remains controversial. Our previous study indicated that although dexamethasone (DEX) exerted anti-inflammatory effects and protected the blood–brain barrier (BBB) by activating the glucocorticoid receptor (GR) after TBI, it also impeded tissue repair processes due to excessive anti-inflammation. Conversely, fludrocortisone, acting as a specific mineralocorticoid receptor (MR) agonist, has shown potential in controlling neuroinflammation and promoting neurorepair, but the underlying mechanisms need further exploration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the impact of the MR agonist fludrocortisone on microglia polarization, angiogenesis, functional rehabilitation, and associated mechanisms after TBI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a mice controlled cortical impact model, and then immunofluorescence staining, western blot, rt-PCR, and MRI were performed to investigate microglia polarization, angiogenesis, and brain edema in the ipsilateral hemisphere after TBI and fludrocortisone treatment. Subsequently, functional tests including morris water maze, sucrose preference test, and forced swimming test were conducted to evaluate the effects of fludrocortisone treatment on neurofunction after TBI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed that fludrocortisone suppressed neuroinflammation, enhanced angiogenesis and neuronal survival, and promoted functional rehabilitation by inducing a shift in microglia phenotype from M1 to M2 via the JAK/STAT6/PPARγ pathway. Additionally, the PI3K/Akt/HIF-1α pathway was involved in VEGF expression and in the process of angiogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Fludrocortisone, the specific MR agonist, exerted anti-neuroinflammatory and neuroprotective effects by regulating phenotypic switching of microglia from M1 to M2 rather than suppressing all types of microglia. Our study provided a theoretical basis for the therapeutic strategy of GCs targeting neuroinflammation after TBI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871598","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":"Data-Driven Subtypes of Parkinson Disease Based on Dopamine Responsiveness","authors":"Jian-Yong Wang,&nbsp;Guo-Ling Zeng,&nbsp;Rong-Ting Tang,&nbsp;Hai-Tao Luo,&nbsp;Yu-Lian Song,&nbsp;Yang-Yang Zhou,&nbsp;Jie-Fan Huang,&nbsp;Shi-Guo Zhu,&nbsp;Dao-Lu Zhang,&nbsp;Dan-Ni Liu,&nbsp;Rong-Pei Liu,&nbsp;Shi-Shi Huang,&nbsp;Cheng-Xiang Yuan,&nbsp;Jian-Hong Zhu,&nbsp;Xiong Zhang","doi":"10.1111/cns.70408","DOIUrl":"https://doi.org/10.1111/cns.70408","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Parkinson disease (PD) is highly heterogeneous in response to antiparkinsonian drugs. We herein aimed to identify PD subtypes based on dopamine responsiveness in three key motor signs (resting tremor, rigidity, and bradykinesia).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The acute levodopa challenge test was performed. Improvement rates in resting tremor, rigidity, and bradykinesia were calculated. A total of 228 PD patients were included for further analysis. Subtypes were determined by k-means clustering based on the improvement rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four subtypes were identified: rt-r-b, moderate improvement in resting tremor, rigidity, and bradykinesia; RT-r-b, marked improvement in resting tremor but moderate improvement in rigidity and bradykinesia; RT-R-B, marked improvement in resting tremor, rigidity, and bradykinesia; rt-R-B, moderate improvement in resting tremor but marked improvement in rigidity and bradykinesia. These subtypes also differed in other motor and nonmotor symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study reveals four distinct subtypes in PD patients based on dopamine responsiveness. Our findings provide a novel insight into understanding PD heterogeneity and facilitate precision treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865761","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":"Anatomical Determinants of STN Coordinate Shift in Idiopathic Parkinson's Disease DBS Surgery","authors":"Ozan Hasimoglu,&nbsp;Tuba Özge Karaçoban,&nbsp;Taha Hanoglu,&nbsp;Nur Bahar Geylan,&nbsp;Ayca Altinkaya,&nbsp;Buruc Erkan,&nbsp;Lütfi Şinasi Postalci,&nbsp;Bekir Tugcu","doi":"10.1111/cns.70307","DOIUrl":"https://doi.org/10.1111/cns.70307","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study examines how anatomical variations influence the targeting coordinates of the subthalamic nucleus (STN) in patients with Idiopathic Parkinson's Disease (IPD) undergoing Deep Brain Stimulation (DBS), with the goal of enhancing targeting accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was performed on 202 STNs from patients who received bilateral STN-DBS surgery. Pre- and postoperative imaging data were used to determine accurate STN coordinates, while brain volume measurements, ventricle size, Evans Index, and AC –PC length were analyzed. Atrophy grading scales were also applied. Correlation and regression analyses assessed the relationship between the STN target location and all anatomical parameters on the <i>x</i>, <i>y</i>, and <i>z</i> axes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Age showed a significant positive correlation with lateral STN coordinate shift on the <i>x</i>-axis, with each additional year leading to a 0.046 mm shift. An increase in peripheral gray matter volume and a decrease in white matter volume were significantly associated with the lateral displacement of the STN. Total ventricle volume demonstrated a positive correlation with STN shift on both the <i>x</i>-axis (0.0227 mm per cm³ increase) and <i>z</i>-axis (0.0087 mm per cm³ increase). Significant correlations were also found for the Evans Index with lateral shift on the <i>x</i>-axis and for AC-PC length with vertical shifts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anatomical factors, such as brain volume, ventricle size, Evans Index, AC-PC length, and atrophy scores, significantly influence STN localization in PD patients undergoing DBS. Accounting for these shifts during surgical planning may improve electrode placement accuracy and enhance therapeutic outcomes, underscoring the importance of personalized targeting strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871779","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":"Dynamic and Static Functional Gradient in Temporal Lobe Epilepsy With Hippocampal Sclerosis Versus Healthy Controls","authors":"Kangrun Wang,&nbsp;JiaYao Li,&nbsp;Fangfang Xie,&nbsp;Chaorong Liu,&nbsp;Langzi Tan,&nbsp;Jialinzi He,&nbsp;Xianghe Liu,&nbsp;Ge Wang,&nbsp;Min Zhang,&nbsp;Haiyun Tang,&nbsp;Danlei Wei,&nbsp;Jingwan Feng,&nbsp;Sha Huang,&nbsp;Jinxin Peng,&nbsp;Zhuanyi Yang,&nbsp;Xiaoyan Long,&nbsp;Bo Xiao,&nbsp;Juan Li,&nbsp;Lili Long","doi":"10.1111/cns.70298","DOIUrl":"https://doi.org/10.1111/cns.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The gradient captures the continuous transitions in connectivity, representing an intrinsic hierarchical architecture of the brain. Previous works hinted at the dynamics of the gradient but did not verify them. Cognitive impairment is a common comorbidity of temporal lobe epilepsy (TLE). Gradient techniques provide a framework that could promote the understanding of the neural correlations of cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty patients with TLE and hippocampal sclerosis and 29 matched healthy controls (HC) were investigated with verbal fluency task-based functional MRI and gradient techniques. The correlation between task-based activation/deactivation and healthy gradients, task-based gradients, and dynamic features calculated with sliding window approaches was compared between HC and TLE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The allegiance in the real data of HC and TLE was more widespread compared to static null models. TLE has lower dynamic recruitment of gradient, atypical activation-gradient correlation, and contracted principal gradient. Correlation analysis proved that the reconfiguration of principal gradient did not drive the reorganization of activation. The atypical activation pattern and impaired recruitment were correlated with cognition scales in TLE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The principal gradient is dynamic. TLE disrupted activation/deactivation patterns, the principal gradient, and the dynamics of the gradient, which were correlated with cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861834","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}