Neuroscience bulletin最新文献

{"title":"Identification of TMED10 as A Regulator for Neuronal Exocytosis of Amyloid Beta 42.","authors":"Peixin Meng, Longze Sha, Xiaolin Yu, Yanbing Wang, Erning Zhang, Kexin Meng, Bingnan Li, Qin Zhao, Qi Xu","doi":"10.1007/s12264-025-01492-3","DOIUrl":"https://doi.org/10.1007/s12264-025-01492-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurotoxic amyloid beta (Aβ) deposition in the brain. Neurons can internalize and exocytose Aβ; however, the molecular pathways governing Aβ release remain poorly understood. To identify key regulators of Aβ42 transport, we applied formaldehyde cross-linking of protein complexes combined with co-immunoprecipitation and mass spectrometry analysis to identify TMED10 as a novel Aβ42-interacting protein. In cultured neurons, TMED10 knockdown (KD) increased intracellular Aβ42 levels by preventing Aβ42 exocytosis. TMED10 expression was significantly reduced in the cortex of AD patients. Overexpression of TMED10 in primary neurons mitigated the toxic effects of exogenous Aβ42. In 5 × FAD mice, overexpression of TMED10 via tail vein injection of a brain-penetrable adeno-associated virus improved cognitive function and reduced Aβ42 plaque accumulation. Together, these findings position TMED10 as a potential regulator of Aβ42 exocytosis and underscore the need for further studies to evaluate its therapeutic potential in AD.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Neural Dynamics of Visual Stream Interactions During Memory-Guided Actions Investigated by Intracranial EEG.","authors":"Sofiia Moraresku, Jiri Hammer, Vasileios Dimakopoulos, Michaela Kajsova, Radek Janca, Petr Jezdik, Adam Kalina, Petr Marusic, Kamil Vlcek","doi":"10.1007/s12264-025-01453-w","DOIUrl":"10.1007/s12264-025-01453-w","url":null,"abstract":"","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1709"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viewing Psychiatric Disorders Through Viruses: Simple Architecture, Burgeoning Implications.","authors":"Lingzhuo Kong, Boqing Zhu, Yifan Zhuang, Jianbo Lai, Shaohua Hu","doi":"10.1007/s12264-025-01443-y","DOIUrl":"10.1007/s12264-025-01443-y","url":null,"abstract":"<p><p>A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades; the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized. However, little research has focused on viruses-entities characterized by smaller dimensions, simpler structures, greater diversity, and more intricate interactions with their surrounding milieu compared to bacteria. To date, alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders, including schizophrenia, major depressive disorder, autism spectrum disorder, and Alzheimer's disease, accompanied by metabolic disruptions that may directly or indirectly impact brain function. In addition, eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses. Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented. However, limitations due to the lack of large-scale cohort studies, reliability, clinical applicability, and the unclear role of viruses in microbiota interactions pose a challenge for future studies. Nevertheless, it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1669-1688"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological Signatures of Visual Sensations Elicited by Direct Electrical Stimulation.","authors":"Yan-Yan Li, Bo Zhang, Jing Wang, Yuri B Saalmann, Mohsen Afrasiabi, Peng-Cheng Lv, Hai-Xiang Wang, Huan-Huan Xiang, Meng-Yang Wang, Guo-Ming Luan, Robert T Knight, Liang Wang","doi":"10.1007/s12264-025-01464-7","DOIUrl":"10.1007/s12264-025-01464-7","url":null,"abstract":"<p><p>Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1617-1629"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: Overexpression of Tau Rescues Nogo-66-Induced Neurite Outgrowth Inhibition In Vitro.","authors":"Yu-Chao Zuo, Hong-Lian Li, Nan-Xiang Xiong, Jian-Ying Shen, Yi-Zhi Huang, Peng Fu, Hong-Yang Zhao","doi":"10.1007/s12264-025-01481-6","DOIUrl":"10.1007/s12264-025-01481-6","url":null,"abstract":"","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1710"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response.","authors":"Ling Zheng, Qiaosen Shen, Tong Zhao, Qingsong Liu, Zihao Huang, Feng Zhao, Mengqian Zhang, Yongdong Song, Daogong Zhang, Dong Liu, Fangyi Chen","doi":"10.1007/s12264-025-01406-3","DOIUrl":"10.1007/s12264-025-01406-3","url":null,"abstract":"<p><p>Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1537-1552"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of the Rich Club Properties in Mouse, Macaque, and Human Brain Networks: A Study of Functional Integration, Segregation, and Balance.","authors":"Xiaoru Zhang, Ming Song, Wentao Jiang, Yuheng Lu, Congying Chu, Wen Li, Haiyan Wang, Weiyang Shi, Yueheng Lan, Tianzi Jiang","doi":"10.1007/s12264-025-01393-5","DOIUrl":"10.1007/s12264-025-01393-5","url":null,"abstract":"<p><p>The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1630-1644"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic Functional Connectivity Associated with γ‑Aminobutyric Acid and Glutamate/Glutamine in the Lateral Prefrontal Cortex and Internalizing Psychopathology in Adolescents.","authors":"Kai Wang, Harry R Smolker, Mark S Brown, Hannah R Snyder, Yu Cheng, Benjamin L Hankin, Marie T Banich","doi":"10.1007/s12264-025-01408-1","DOIUrl":"10.1007/s12264-025-01408-1","url":null,"abstract":"<p><p>In this study, we systematically tested the hypothesis that during the critical developmental period of adolescence, on a macro scale, the concentrations of major excitatory and inhibitory neurotransmitters (glutamate/glutamine and γ‑aminobutyric acid [GABA]) in the dorsal and ventral lateral prefrontal cortex are associated with the brain's functional connectivity and an individual's psychopathology. Neurotransmitters were measured via magnetic resonance spectroscopy while functional connectivity was measured with resting-state fMRI (n = 121). Seed-based and network-based analyses revealed associations of neurotransmitter concentrations and functional connectivities between regions/networks that are connected to prefrontal cortices via structural connections that are thought to be under dynamic development during adolescence. These regions tend to be boundary areas between functional networks. Furthermore, several connectivities were found to be associated with individual's levels of internalizing psychopathology. These findings provide insights into specific neurochemical mechanisms underlying the brain's macroscale functional organization, its development during adolescence, and its potential associations with symptoms associated with internalizing psychopathology.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1553-1569"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological Abnormalities and Pharmacological Corrections of Pathogenic Missense Variants in KCNQ3.","authors":"Xiaorong Wu, Jili Gong, Li Qiu, Guimei Yang, Hui Yuan, Xiangchun Shen, Yanwen Shen, Fuyun Tian, Zhaobing Gao","doi":"10.1007/s12264-025-01378-4","DOIUrl":"10.1007/s12264-025-01378-4","url":null,"abstract":"<p><p>The KCNQ potassium channels play a crucial role in modulating neural excitability, and their dysfunction is closely associated with epileptic disorders. While variants in KCNQ2 have been extensively studied, KCNQ3-related disorders have rarely been reported. With advances in next-generation sequencing technologies, an increasing number of cases of KCNQ3-related disorders have been identified. However, the correlation between genotype and phenotype remains poorly understood. In this study, we established a variant library consisting of 24 missense mutations in KCNQ3 and introduced these mutations into three different template types: KCNQ3, KCNQ3-A315T (Q3*), and KCNQ3-KCNQ2 tandem (Q3-Q2). We then analyzed the effects of these mutations on the KCNQ3 channel function using patch-clamp recording. The most informative parameter across all three backgrounds was the current density of the mutant channels. The current density patterns in the Q3* and Q3-Q2 backgrounds were similar, with most mutations resulting in an almost complete loss of function (LOF), they were concentrated in the pore-forming domain of KCNQ3. In contrast, mutations in the voltage-sensing domain or C-terminus did not show significant differences from the wild-type channel. Interestingly, these LOF mutations were typically associated with self-limited familial neonatal epilepsy, while neurodevelopmental disorders (NDD) were more closely associated with mutations that did not significantly differ from the wild-type. V_1/2, another important parameter of the electrophysiological properties, could not be accurately determined in the majority of KCNQ3 mutations due to its nearly complete LOF in the Q3* and Q3-Q2 backgrounds. Intriguingly, the V_1/2 of functional mutations were primarily leftward shifted, indicating a gain-of-function (GOF) effect, which was typically associated with NDD. In addition to previously reported mutations, we identified G553R as a novel GOF mutation. In the co-transfection background, parameters such as V_1/2 could be determined, but the dysfunctional effects of these mutations were mitigated by the co-expression of wild-type KCNQ3 and KCNQ2 subunits, resulting in no significant differences between most mutations and the wild-type channel. Furthermore, we applied KCNQ modulators to reverse the electrophysiological abnormalities caused by KCNQ3 variants. The LOF mutations were reversed by the application of Pynegabine (HN37), a KCNQ opener, while the GOF mutation responded well to Amitriptyline (AMI), a KCNQ inhibitor. These findings provide essential insights into the pathogenic mechanisms underlying KCNQ3-related disorders and may inform clinical decision-making.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1511-1521"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic Protein Lactylation: A Novel Mechanism Underlying Physical Exercise-mediated Stress Resilience.","authors":"Can-Yuan Zhang, Su-Fen Wei, Xiong Cao","doi":"10.1007/s12264-025-01467-4","DOIUrl":"10.1007/s12264-025-01467-4","url":null,"abstract":"","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1705-1708"},"PeriodicalIF":5.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}