CNS Neuroscience & Therapeutics最新文献

{"title":"Activation of Locus Coeruleus-Hippocampus Tyrosine Hydroxylase Projection Contributes to the Surgical Incision Pain-Induced Memory Consolidation Enhancement in Mice","authors":"Xin Qing,&nbsp;Jinyang Liu,&nbsp;Yinyao Feng,&nbsp;Luyao Zhang,&nbsp;Jiawei Sun,&nbsp;Peng Wang,&nbsp;Zhilai Yang,&nbsp;Jiqian Zhang,&nbsp;Hu Liu,&nbsp;Xuesheng Liu","doi":"10.1111/cns.70570","DOIUrl":"https://doi.org/10.1111/cns.70570","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The mechanism underlying postoperative post-traumatic stress disorder (PTSD) remains unclear. However, studies have shown that acute postoperative pain is an independent risk factor for PTSD, which is also closely related to memory consolidation enhancement. Preoperative patients often experience unpleasant traumatic events, and postoperative pain usually occurs in the memory consolidation stage of these events. Therefore, inquiring whether acute postoperative pain affects memory consolidation and its possible mechanism may help to explain the causes of postoperative PTSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>In this study, we show that the surgical incision pain enhances the consolidation of emotional memory (in the passive avoidance test) and nonemotional memory (in the novel object recognition test) in mice. None of the behaviors evaluated were affected by anxiety or locomotor dysfunction (in the open-field test). Besides, we confirmed that surgical incision pain promotes memory enhancement by enhancing memory consolidation instead of memory retrieval. Furthermore, the consolidation of emotional memory and nonemotional memory was enhanced by the activation of the LC-HPC TH projection after surgical incision pain. Hippocampal CA1 dopamine receptors, rather than β adrenoceptors, mediate emotional and nonemotional memory consolidation enhancement after surgical incision pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, our results indicate that surgical incision pain enhances the memory consolidation of emotional memory and nonemotional memory in mice. Activation of the LC-HPC TH projection may contribute to memory consolidation enhancement induced by surgical incision pain, which involves the activity of dopamine receptors in CA1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934966","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 Transformer-Based Framework With Data Augmentation for Robust Seizure Detection Across Invasive and Noninvasive Neural Recordings","authors":"Yue Yuan,&nbsp;Junyang Zhang,&nbsp;Chen Wang,&nbsp;Hao Yan,&nbsp;Xiangyu Ye,&nbsp;Wenjun Ruan,&nbsp;Xinzhuo Teng,&nbsp;Zheshan Guo,&nbsp;Zhaoxiang Wang","doi":"10.1111/cns.70584","DOIUrl":"https://doi.org/10.1111/cns.70584","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Epilepsy affects more than 50 million peolple worldwide and requires reliable seizure detection systems to mitigate risks associated with unpredictable seizures. Existing machine learning frameworks are limited in generalizability, signal fidelity, and clinical translation, particularly when bridging invasive and non-invasive modalities. This study aims to develop a robust and generalizable seizure detection model capable of supporting cross-modal applicability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We proposed a Transformer-based seizure detection framework designed for end-to-end analysis of raw neurophysiological signals. To address class imbalance and temporal variability, three data augmentation strategies: sequential sampling, random contiguous sampling, and random non-contiguous sampling, were implemented. A channel-agnostic attention mechanism was incorporated to ensure robustness across heterogeneous electrode configurations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The framework achieved &gt; 99% accuracy in detecting diverse seizure patterns from rat hippocampal recordings (CA1/CA3) and maintained strong performance across different epilepsy models (PTX- and 4-AP-induced seizures). It also demonstrated resilience under reduced-channel configurations (F1-score: 98.7% with 2 channels). In human electroencephalography (EEG) validation, the model achieved a recall of 99.1% and an overall accuracy of 90.4%, despite the inherent limitations of EEG in resolving high-frequency oscillations and its susceptibility to artifacts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By eliminating manual feature engineering and enabling robust cross-modal adaptation, this framework bridges invasive experimental research and non-invasive clinical practice. Its efficiency and scalability support potential applications in real-time seizure monitoring and closed-loop neuromodulation systems. Future work will focus on integration with hemodynamic biomarkers, validation in chronic epilepsy models, and optimization for wearable and real-time deployment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935365","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":"Endothelin-Converting Enzyme-Like 1 Regulated by LIF Contributes to Chronic Constriction Injury-Induced Neuropathic Pain in Mice","authors":"Feng Gao,&nbsp;Yuchen Pan,&nbsp;Yong Huang,&nbsp;Chen Gu,&nbsp;Xiaowei Song,&nbsp;Cunjin Wang","doi":"10.1111/cns.70578","DOIUrl":"https://doi.org/10.1111/cns.70578","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study is to investigate the role of Endothelin-converting enzyme-like 1 (ECEL1) in neuropathic pain (NP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of ECEL1 was modulated by injecting adeno-associated virus 5 (AAV5) carrying Ecel1 shRNA or full-length Ecel1 into the dorsal root ganglion (DRG) of mice with a chronic constriction injury (CCI) model. Then, various nociceptive responses were evaluated. Additionally, leukemia inhibitory factor (LIF) was intrathecally injected, or its function was blocked, to observe the changes in ECEL1 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings demonstrate that downregulating ECEL1 expression alleviates CCI-induced pain and reduces the hyperexcitability of injured DRG neurons, which is achieved by inhibiting sympathetic sprouting in the DRG. Conversely, overexpressing ECEL1 in DRG neurons leads to pain hypersensitivity. Additionally, we observed that LIF upregulated ECEL1 expression, while blocking LIF reduced ECEL1 expression and mitigated CCI-induced nociception in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ECEL1 promotes hyperalgesia following CCI and is regulated by LIF, suggesting it could be a new target for NP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935366","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 Effects of PLGA Nanoparticles Containing Different Growth Factors on Neural Stem Cell Differentiation and Their Transition Efficiency After Targeting With TRF","authors":"Ayşegül Açıksarı,&nbsp;Yusufhan Yazır,&nbsp;Serap Mert,&nbsp;Zehra Seda Halbutoğulları,&nbsp;Sümeyye Narin,&nbsp;Gülçin Gacar","doi":"10.1111/cns.70576","DOIUrl":"https://doi.org/10.1111/cns.70576","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Nanoparticle-mediated drug delivery systems are being investigated for the controlled release of drugs to treat neurodegenerative diseases (ND). We aimed to investigate the effects of poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing different growth factors (GFs) on rat brain-derived neural stem cells (NSCs) in vitro differentiation, providing insights that may contribute to future approaches for treating Parkinson's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three different PLGA-NPs loaded with Brain-Derived Neurotrophic Factor (BDNF), Glial-Derived Neurotrophic Factor (GDNF), and Transforming Growth Factor beta 3 (TGF-β3) were developed and characterized in terms of size, zeta potential, encapsulation efficiency, and release profile. These NPs were used to differentiate NSCs into dopaminergic neurons in vitro. Additionally, the transition of transferrin (TRF)-conjugated PLGA-COOH-NPs across an in vitro blood–brain barrier (BBB) model was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average sizes of BDNF, GDNF, and TGF-ß3 loaded PLGA-NPs were measured to be 217.17 ± 1.37, 227.37 ± 5.39, and 220.57 ± 10.10 nm, respectively. Besides, SEM imaging revealed that the particles had a homogeneous size distribution and smooth surface morphology. Microtubule-associated protein 2 (Map2) and tyrosine hydroxylase (TH), two dopaminergic neuronal markers, were found in cells with neuron-like morphology that were produced through in vitro differentiation. The cellular uptake of PLGA-NPs loaded with Coumarin-6 was determined by using confocal imaging and flow cytometry. It was demonstrated that TRF-conjugated NPs were specifically targeted and taken up into NSCs in the in vitro BBB model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It is concluded that BDNF-PLGA-NPs, GDNF-PLGA-NPs, and TGF-ß3-PLGA-NPs are promising brain drug delivery carriers for NSC inducers, which could be useful in developing strategies for Parkinson's disease management, particularly when targeted with TRF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935074","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":"Triptolide Inhibits Epileptic Seizures by Rescuing the Neuroinflammation-Related GABAergic Dysfunction in Mice","authors":"Haimei Lu,&nbsp;Yijun Luo,&nbsp;Mingxuan Han,&nbsp;Yitian Lan,&nbsp;Wenmi Li,&nbsp;Xiu Yu,&nbsp;Xiaoyu Wang,&nbsp;Rongrong Chen,&nbsp;Huawei Zhao,&nbsp;Zhenghao Xu","doi":"10.1111/cns.70586","DOIUrl":"https://doi.org/10.1111/cns.70586","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to evaluate the antiepileptic effect of triptolide (TPL), a strong anti-inflammatory and immunosuppressive diterpenoid compound from a Chinese herb medicine Tripterygium wilfordii Hook F (TWHF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The pentylenetetrazol (PTZ)-induced seizure model, maximal electroshock seizure (MES) model, corneal (6 Hz) kindling model, and kainic acid (KA) mouse model were used to assess the antiepileptic effect of TPL. EEG recording and behavioral tests were used to evaluate the disease-modifying effects of TPL in epileptic conditions. Extracellular recording combined with optogenetics was used to evaluate the effect of TPL on hippocampal GABAergic inhibition in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Though intragastric administration of TPL (50 μg/kg) had no direct anticonvulsive effect in normal mice, it retarded corneal kindling acquisition in mice and reduced the seizure severity in corneal kindled mice. Meanwhile, intragastric administration (10 or 50 μg/kg) of TPL exhibited disease-modifying effects in the established KA mouse model of temporal lobe epilepsy (TLE). Extracellular recording combined with optogenetics showed that TPL improved the hippocampal GABAergic “braking effect” in epileptic mice. Furthermore, bioinformatics analysis predicts IL-1β as a key target for the antiepileptic effect of TPL. TPL reduced the level of IL-1β in the hippocampus of KA-induced epileptic mice, while focal injection of IL-1β (5 ng in 1 μL saline) attenuated the hippocampal GABAergic “braking effect” in normal mice. Focal injection of TPCA-1 (an IKK-2/NF-κB inhibitor, 600 ng in 1 μL 1% DMSO) partly recovered the IL-1β-induced attenuation of the GABAergic “braking effect”.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicates that a low dose of TPL may inhibit epilepsy by potentially rescuing dysfunction in hippocampal GABAergic neural circuits related to neuroinflammation in mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915126","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":"Tenuifolin Attenuates Methamphetamine-Induced Reinstatement in Mice by Regulating Hippocampal Postsynaptic BDNF Signaling","authors":"Yize Qi,&nbsp;Shuyuan Fan,&nbsp;Yu Sun,&nbsp;Hanqing Shi,&nbsp;Hailing Li,&nbsp;Gang Xiao,&nbsp;Qingfeng Shen","doi":"10.1111/cns.70588","DOIUrl":"https://doi.org/10.1111/cns.70588","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Compulsive relapse (reinstatement) behavior of methamphetamine underlies the difficulty of withdrawal and is associated with abnormal BDNF-mediated synaptic plasticity. However, how to intervene in this aberrant synaptic plasticity to prevent its reinstatement behavior in mice has not fully been studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The CPP was used to establish a model of methamphetamine-induced reinstatement behavior in C57BL/6 mice. Intraperitoneal injections of TEN were administered during the remission phase after the successful establishment of the CPP model to investigate the therapeutic effects on reinstatement. Immunofluorescence experiments were used to detect c-fos expression in hippocampal CA1 neurons. Electrophysiological methods were used to determine glutamatergic transmission in hippocampal CA1 neural circuits. Western blotting was used to detect BDNF/TrKB and PSD-95 protein expressions. Molecular docking was used to predict TEN molecule–protein binding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with control mice, METH-treated mice presented increased CPP scores during the reinstatement phase, whereas, compared to METH-treated mice, TEN-treated mice presented significantly lower CPP scores. Immunofluorescence experiments indicated that TEN was able to inhibit the METH-induced increase in c-fos content. In addition, we found that TEN alleviates the METH-triggered increase in glutamatergic transmission in mouse hippocampal CA1 neurons. Importantly, molecular docking studies demonstrated that TEN binds with BDNF, which may be important targets for its biological function. We also demonstrated that interfering with BDNF inhibits the therapeutic effect of TEN on the reinstatement of METH addiction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that TEN treats METH-induced reinstatement behavior by binding to BDNF, which may provide a novel target for treating relapse in patients addicted to METH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910265","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":"Targeting Drp1 in Cerebral Ischemia–Reperfusion Injury: Mechanisms and Therapeutic Implications","authors":"Mengnan Liu,&nbsp;Zhixue Yin,&nbsp;Binru Li,&nbsp;Ji Qiu,&nbsp;Dechou Zhang,&nbsp;Raoqiong Wang,&nbsp;Xue Bai,&nbsp;Li Chen","doi":"10.1111/cns.70590","DOIUrl":"https://doi.org/10.1111/cns.70590","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral ischemia-reperfusion injury (CIRI) arises after blood flow restoration in stroke, where reperfusion paradoxically triggers mitochondrial dysfunction, apoptosis, inflammation, and oxidative stress. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, amplifies these cascades by promoting apoptosis, inflammatory signaling, and calcium imbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review synthesizes recent studies on Drp1 in CIRI, focusing on its regulatory roles in mitochondrial dynamics and neuronal injury, and evaluating therapeutic strategies through pharmacological and genetic modulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Evidence shows Drp1 inhibition mitigates CIRI in preclinical models by restoring mitochondrial homeostasis, reducing oxidative stress, and improving neuronal survival. Promising interventions include selective inhibitors and genetic approaches, though challenges remain regarding drug specificity, delivery efficiency, and long-term safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Drp1 is central to CIRI pathology and represents a promising therapeutic target. Future work should prioritize advanced delivery systems and safer, more selective Drp1 modulators to enable clinical translation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915171","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 Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice","authors":"Zhixin Wu,&nbsp;Dongkun Xie,&nbsp;Jing Zhao,&nbsp;Jianshuai Zhao,&nbsp;Huiqing Liu,&nbsp;Dong Xing,&nbsp;Tingting Gu,&nbsp;Yaru Guo,&nbsp;Dan Wang,&nbsp;Zhihong Lu,&nbsp;Hailong Dong,&nbsp;Junlong Zhao,&nbsp;Jiao Deng","doi":"10.1111/cns.70454","DOIUrl":"https://doi.org/10.1111/cns.70454","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;Perioperative cognitive disorder (PND) affects up to 31% of surgical patients. Although clinical studies have identified a variety of risk factors, no effective prevention has been developed. From our previous cohort of PND patients, several single-nucleotide polymorphism (SNP) sites on &lt;i&gt;ctnna2&lt;/i&gt; were identified. The current study aims to decipher the role and regulatory mechanism of &lt;i&gt;ctnna2&lt;/i&gt; in the PND model and to develop decoy oligodeoxynucleotides (decoy) for the possible prevention of PND.&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;Both mice model (exploratory laparotomy+isoflurane) and the neuronal model (TNFα+isoflurane, T + I) for PND were used. Bioinformatic research was utilized to identify transcriptive active areas on &lt;i&gt;ctnna2&lt;/i&gt;, &lt;i&gt;foxo3&lt;/i&gt; sequence, and to predict possible transcriptional factors for regulation. Molecular biological techniques were used to decipher the regulatory mechanism and specific sites of the Sirt1-foxo3-ctnna2 axis in the development of PND. Finally, an decoy targeting the Foxo3-ctnna2 interaction was designed and tested for effectiveness in PND.&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;Our results showed that the SNP rs12472215 is located at a newly defined enhancer region within the &lt;i&gt;ctnna2&lt;/i&gt; intron that can be regulated by Foxo3 in the human genome. The rs12472215 A&gt;T mutation potentiates Foxo3's transcriptive inhibitory effect on &lt;i&gt;ctnna2&lt;/i&gt;. Experimental laparotomy in mice revealed that hippocampal Foxo3 upregulation and α-N-catenin reduction are involved in PND development. ChIP-PCR deciphered two regulatory sites (R1 and R2) of Foxo3 on &lt;i&gt;ctnna2&lt;/i&gt; in the mice that are strengthened by T + I. siAscl1 abolished the rescue effect of carbenoxolone (CBX, Foxo3-specific inhibitor) on α-N-catenin expression in the T + I model, indicating that Foxo3 inhibits &lt;i&gt;ctnna2&lt;/i&gt; transcription indirectly through Ascl1. Reduction of Sirt1 increased acetyl-Foxo3, which enhanced its stability in PND. Sirt1 activation reduced Foxo3 expression, acetyl-Foxo3 level, and rescued α-N-catenin expression in T + I stimulated neurons. More importantly, the new decoy disturbing Foxo3-ctnna2 interaction effectively prevents α-N-catenin reduction, CA1 pyramidal neuron morphological change, electrophysiological dysfunction, and improves cognitive deficit in PND mice.&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;These results provided a new revenue for identifying targets and developing interventions for PND. The decoy, due to its specificity and short acting ti","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905553","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":"Effective Connectivity Predicts Surgical Outcomes in Temporal Lobe Epilepsy: A SEEG Study","authors":"Xu Hu,&nbsp;Yuan Yao,&nbsp;Baotian Zhao,&nbsp;Xiu Wang,&nbsp;Zilin Li,&nbsp;Wenhan Hu,&nbsp;Chao Zhang,&nbsp;Kai Zhang","doi":"10.1111/cns.70563","DOIUrl":"https://doi.org/10.1111/cns.70563","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Temporal lobe epilepsy (TLE), the most common type of drug-resistant epilepsy (DRE), has a postoperative seizure-free rate of ~70%. Furthermore, precisely localizing the epileptogenic zone and determining the surgical resection area have been established as the key factors influencing surgical outcomes. Herein, we innovatively coupled the surgical resection area with characteristics of effective connectivity via intracranial electroencephalography (iEEG) to predict patients' surgical prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study involved 56 patients who underwent TLE surgery and were followed up for over 1 year. All patients underwent stereo-electroencephalography (SEEG) electrode implantation and single-pulse electrical stimulation (SPES) tests. After comparing patients' RMS value of N1/N2 (Z-score standardized) from cortico-cortical evoked potentials (CCEP) with different surgical outcomes, an interpretable machine learning (ML) model based on support vector machine (SVM) for predicting patients' surgical prognosis was constructed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with various surgical outcomes exhibited differences in effective connectivity. Furthermore, compared to the seizure-free group (Engel I), patients in the nonseizure-free group (Engel II-IV) exhibited stronger connectivity between the seizure onset zone (SOZ) and regions outside the surgical resection area. The nonseizure-free group also exhibited stronger connectivity between the surgical resection area and regions outside the resection area. Our prediction model demonstrated high-accuracy performance, with accuracy and area under the curve (AUC) values of 0.800 and 0.893, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study confirmed the potential value of integrating the surgical resection area and effective connectivity characteristics in predicting patients' surgical outcomes; offering a novel approach that could be leveraged to precisely determine the surgical resection area and improve TLE patients' surgical prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897410","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":"Regulation of Somatosensory Temporal Discrimination Threshold Through Motor Training: An EEG and Kinematics Study","authors":"Jinyan Zhang,&nbsp;Wangjun Zou,&nbsp;Binbin Gao,&nbsp;Jinglong Wu,&nbsp;Zhilin Zhang,&nbsp;Jian Zhang,&nbsp;Luyao Wang,&nbsp;Tianyi Yan","doi":"10.1111/cns.70564","DOIUrl":"https://doi.org/10.1111/cns.70564","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Motor training enhances somatosensory temporal discrimination threshold (STDT), but the distinct neural mechanisms underlying actual execution versus motor imagery remain unclear. This study aimed to compare the effects of ball-rotation training (BRT; actual execution) and visual-guided imagery (VGI; motor imagery) on STDT, kinematic performance, and neurophysiological plasticity in healthy adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight right-handed participants were randomized into four groups: BRT (actual execution), VGI (motor imagery without movement), tactile control (simple gripping), and no-intervention control. Over seven days, participants underwent pre-/post-training assessments including kinematic analysis, STDT measurement, power spectral analysis and somatosensory-evoked potentials (SEPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BRT significantly enhanced motor performance (83% score increase vs. 21% in controls, <i>p</i> &lt; 0.001) and movement speed (37% cycle time reduction vs. 12%–16% in others, <i>p</i> &lt; 0.001), with partial transfer to the untrained hand. Both interventions reduced STDT but at distinct locations: BRT selectively improved index finger discrimination (64.02 ms → 43.75 ms, <i>p</i> = 0.007), while VGI enhanced palm sensitivity (73.43 ms → 61.13 ms, <i>p</i> = 0.003). Neurophysiologically, SEPs revealed increased spatial inhibition ratio (SIR) plasticity in both BRT and VGI (<i>p</i> &lt; 0.001), correlating with STDT gains. EEG demonstrated BRT-induced gamma-band power increases in parietal regions and theta-band elevations in prefrontal cortex, whereas VGI modulated delta-band activity in ipsilateral parietal cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Actual execution (BRT) and motor imagery (VGI) enhance STDT through distinct neuroplastic mechanisms: BRT optimizes sensorimotor integration via parietal gamma/prefrontal theta oscillations, while VGI relies on ipsilateral parietal delta modulation. These findings underscore the role of cortical reorganization in motor learning and support tailored rehabilitation strategies for neurological disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897661","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}