Lu Ding, Xinyue Li, YaQin Guo, Feng-Quan Zhou, David Y B Deng
{"title":"Complement C3a Suppresses Spinal Cord Neural Stem Cell Activation by Inhibiting UCHL1 via the NF-κB p65/Nrf2 Pathway.","authors":"Lu Ding, Xinyue Li, YaQin Guo, Feng-Quan Zhou, David Y B Deng","doi":"10.1007/s12264-025-01488-z","DOIUrl":"https://doi.org/10.1007/s12264-025-01488-z","url":null,"abstract":"<p><p>Activation of spinal cord neural stem cells (NSCs) and subsequent neurogenesis holds a promising alternative for spinal cord injury (SCI) repair. Our previous study demonstrated that complement C3a, derived from reactive astrocytes, inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1 (UCHL1)-proteasome system post-SCI. However, the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear. Here, we revealed that C3a/C3a receptor (C3aR) signaling activated NF-κB p65, which in turn inhibited Nrf2 activity and UCHL1 expression, resulting in diminished proteasome activity and the accumulation of protein aggregates, and ultimately impaired NSC activation. Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro, promoting NSC activation by enhancing protein aggregate clearance. Mechanistically, we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism: (1) promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2; (2) inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation. Using the dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) analysis, we further identified UCHL1 as a direct transcriptional target of Nrf2. Importantly, in vivo experiments using SCI mice confirmed that either C3aR blockade, NF-κB p65 knockdown, or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation. Together, this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI. This may provide novel molecular targets and intervention strategies for SCI repair.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225496","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-06-25DOI: 10.1007/s12264-025-01439-8
Tingting Liu, Haojie Wu, Jianshe Wei
{"title":"Bridging the Gap: The Neuro-immune Axis as a Key Player in Neurodegenerative Disorders.","authors":"Tingting Liu, Haojie Wu, Jianshe Wei","doi":"10.1007/s12264-025-01439-8","DOIUrl":"10.1007/s12264-025-01439-8","url":null,"abstract":"<p><p>Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases. Furthermore, it explores the potential therapeutic applications of targeting the neuro-immune axis for the management and treatment of these diseases. This extensive examination aims to offer new perspectives and innovative strategies that could pave the way for more effective treatments for neurodegenerative diseases, thereby providing hope for those afflicted by these challenging conditions.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1867-1887"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485210","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-07-21DOI: 10.1007/s12264-025-01458-5
Jiamin Bu, Guangwei Xu, Yifeng Zhou
{"title":"Parvalbumin and Somatostatin Neurons in the Thalamic Reticular Nucleus Modulate Visual Information Processing in V1 of Mouse.","authors":"Jiamin Bu, Guangwei Xu, Yifeng Zhou","doi":"10.1007/s12264-025-01458-5","DOIUrl":"10.1007/s12264-025-01458-5","url":null,"abstract":"<p><p>The thalamic reticular nucleus (TRN) plays a crucial role in regulating sensory encoding, even at the earliest stages of visual processing, as evidenced by numerous studies. Orientation selectivity, a vital neural response, is essential for detecting objects through edge perception. Here, we demonstrate that somatostatin (SOM)-expressing and parvalbumin (PV)-expressing neurons in the TRN project to the dorsal lateral geniculate nucleus and modulate orientation selectivity and the capacity for visual information processing in the primary visual cortex (V1). These findings show that SOM-positive and PV-positive neurons in the TRN are powerful modulators of visual information encoding in V1, revealing a novel role for this thalamic nucleus in influencing visual processing.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1824-1842"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675374","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-07-15DOI: 10.1007/s12264-025-01455-8
Jinru Xin, Xinmiao Wang, Xuechun Meng, Ling Liu, Mingqing Liu, Huangrui Xiong, Aiping Liu, Ji Liu
{"title":"Combined Study of Behavior and Spike Discharges Associated with Negative Emotions in Mice.","authors":"Jinru Xin, Xinmiao Wang, Xuechun Meng, Ling Liu, Mingqing Liu, Huangrui Xiong, Aiping Liu, Ji Liu","doi":"10.1007/s12264-025-01455-8","DOIUrl":"10.1007/s12264-025-01455-8","url":null,"abstract":"<p><p>In modern society, people are increasingly exposed to chronic stress, leading to various mental disorders. However, the activities of brain regions, especially neural firing patterns related to specific behaviors, remain unclear. In this study, we introduce a novel approach, NeuroSync, which integrates open-field behavioral testing with electrophysiological recordings from emotion-related brain regions, specifically the central amygdala and the paraventricular nucleus of the hypothalamus, to explore the mechanisms of negative emotions induced by chronic stress in mice. By applying machine vision techniques, we quantified behaviors in the open field, and signal processing algorithms elucidated the neural underpinnings of the observed behaviors. Synchronizing behavioral and electrophysiological data revealed significant correlations between neural firing patterns and stress-related behaviors, providing insights into real-time brain activity underlying behavioral responses. This research combines deep learning and machine learning to synchronize high-resolution video and electrophysiological data, offering new insights into neural-behavioral dynamics under chronic stress conditions.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1843-1860"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642970","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":"Liquid-Liquid Phase Separation in Hereditary Hearing Loss.","authors":"Kefan Tao, Yanjun Zong, Xiaozhou Liu, Xinyu Shi, Zhengdong Zhao, Yu Sun","doi":"10.1007/s12264-025-01446-9","DOIUrl":"10.1007/s12264-025-01446-9","url":null,"abstract":"<p><p>Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system. Liquid-liquid phase separation (LLPS) is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates. Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss. Nevertheless, there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss. In this review, we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss, specifically focusing on its effects on mechanoelectrical transduction in hair bundles, transcriptional regulation, post-transcriptional modifications, the actin cytoskeleton, ion homeostasis within the inner ear, and energy and redox homeostasis. Furthermore, we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1888-1900"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591852","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":"Physical Activity and Depressive Mood Share the Structural Connectivity Between Motor and Reward Networks.","authors":"Shiqi Di, Na Luo, Weiyang Shi, Zhengyi Yang, Jing Sui, Rongtao Jiang, Yue Cui, Zongchang Du, Jiaqi Zhang, Yawei Ma, Haiyan Wang, Congying Chu, Yuejia Zhong, Wen Li, Yuheng Lu, Hao Yan, Jinmin Liao, Dai Zhang, Vince Calhoun, Ming Song, Tianzi Jiang","doi":"10.1007/s12264-025-01501-5","DOIUrl":"https://doi.org/10.1007/s12264-025-01501-5","url":null,"abstract":"<p><p>In various studies, exercise has been revealed to have a positive effect on alleviating depressive symptoms. However, the neural basis behind this phenomenon remains unknown, as well as its underlying biological mechanism. In this study, we used a large neuroimaging cohort [n = 1,027, major depressive disorder (MDD)/healthy controls (HCs) = 492/535] from the UK Biobank to identify structural connectivity (SC) patterns simultaneously linked with physical activity and depression, as well as the biological interpretation. An SC pattern linked with exercise was identified to be both significantly correlated with depressive mood and group discrimination between MDDs and HCs, primarily located between the motor-related regions and reward-related regions. This pattern was associated with multiple neurotransmitter receptors, such as serotonin and GABA receptors, and enriched in pathways like synaptic signaling and the astrocyte cell type. The SC pattern and genetic results were also replicated in another independent MDD dataset (n = 3,496) and present commonalities with bipolar disorder (n = 81). Overall, these findings not only initially identified a reproducible shared SC pattern between physical activity and depressive mood, but also elucidated the underlying biological mechanisms, which enhance our understanding of how exercise helps alleviate depression and may inform the development of novel neuromodulation targets.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207050","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-04-30DOI: 10.1007/s12264-025-01397-1
Yaqian Fan, Yao Tian, Junhai Han
{"title":"The Glutamate-gated Chloride Channel Facilitates Sleep by Enhancing the Excitability of Two Pairs of Neurons in the Ventral Nerve Cord of Drosophila.","authors":"Yaqian Fan, Yao Tian, Junhai Han","doi":"10.1007/s12264-025-01397-1","DOIUrl":"10.1007/s12264-025-01397-1","url":null,"abstract":"<p><p>Sleep, an essential and evolutionarily conserved behavior, is regulated by numerous neurotransmitter systems. In mammals, glutamate serves as the wake-promoting signaling agent, whereas in Drosophila, it functions as the sleep-promoting signal. However, the precise molecular and cellular mechanisms through which glutamate promotes sleep remain elusive. Our study reveals that disruption of glutamate signaling significantly diminishes nocturnal sleep, and a neural cell-specific knockdown of the glutamate-gated chloride channel (GluClα) markedly reduces nocturnal sleep. We identified two pairs of neurons in the ventral nerve cord (VNC) that receive glutamate signaling input, and the GluClα derived from these neurons is crucial for sleep promotion. Furthermore, we demonstrated that GluClα mediates the glutamate-gated inhibitory input to these VNC neurons, thereby promoting sleep. Our findings elucidate that GluClα enhances nocturnal sleep by mediating the glutamate-gated inhibitory input to two pairs of VNC neurons, providing insights into the mechanism of sleep promotion in Drosophila.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1729-1742"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983582","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-08-04DOI: 10.1007/s12264-025-01444-x
Sha Liu, Quyang Yang, Pengfei Zhu, Xuan Liu, Qingbo Lu, Jie Yang, Jingyao Gao, Hongbin Han, Zhijun Zhang, Ning Gu, Tao Tan, Jianfei Sun
{"title":"Precise Magnetic Stimulation of the Paraventricular Nucleus Improves Sociability in a Mouse Model of ASD.","authors":"Sha Liu, Quyang Yang, Pengfei Zhu, Xuan Liu, Qingbo Lu, Jie Yang, Jingyao Gao, Hongbin Han, Zhijun Zhang, Ning Gu, Tao Tan, Jianfei Sun","doi":"10.1007/s12264-025-01444-x","DOIUrl":"10.1007/s12264-025-01444-x","url":null,"abstract":"<p><p>Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1711-1728"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784891","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}