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Piezo1 Mediates Ultrasound-Stimulated Dopaminergic Neuron Protection via Synaptic Vesicle Recycling and Ferroptosis Inhibition. 压电1通过突触囊泡循环和铁下垂抑制介导超声刺激的多巴胺能神经元保护。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-29 DOI: 10.1007/s12264-025-01420-5
Tian Xu, Li Zhang, Xiaoxiao Lu, Wei Ji, Kaidong Chen
{"title":"Piezo1 Mediates Ultrasound-Stimulated Dopaminergic Neuron Protection via Synaptic Vesicle Recycling and Ferroptosis Inhibition.","authors":"Tian Xu, Li Zhang, Xiaoxiao Lu, Wei Ji, Kaidong Chen","doi":"10.1007/s12264-025-01420-5","DOIUrl":"https://doi.org/10.1007/s12264-025-01420-5","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) and dysregulated synaptic vesicle (SV) recycling. Emerging evidence suggests that ferroptosis is the target of PD therapy. However, the identification of effective anti-ferroptosis treatments remains elusive. This study explores the therapeutic potential of low-intensity ultrasound (US) in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD. We demonstrate that optimized US stimulation (610 kHz, 0.2 W/cm<sup>2</sup>) activates Piezo1 channel-mediated fast endophilin-mediated endocytosis, which promotes SV recycling and synaptic function, presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents. Repaired SV recycling in turn reduces the accumulation of α-syn expression and ferroptotic cell death. These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173913","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}
引用次数: 0
In Vitro and Animal Studies of Human Natural Killer Cell-Derived Exosomes for the Treatment of Otitis Media. 人自然杀伤细胞衍生外泌体治疗中耳炎的体外和动物研究。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-27 DOI: 10.1007/s12264-025-01423-2
Zirui Zhao, Liqin Wang, Zhen Guo, Kanglun Jiang, Jianghong Xu, Yilai Shu, Christina Y Xu, Jianning Zhang, Yunfeng Wang, Geng-Lin Li
{"title":"In Vitro and Animal Studies of Human Natural Killer Cell-Derived Exosomes for the Treatment of Otitis Media.","authors":"Zirui Zhao, Liqin Wang, Zhen Guo, Kanglun Jiang, Jianghong Xu, Yilai Shu, Christina Y Xu, Jianning Zhang, Yunfeng Wang, Geng-Lin Li","doi":"10.1007/s12264-025-01423-2","DOIUrl":"https://doi.org/10.1007/s12264-025-01423-2","url":null,"abstract":"<p><p>Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151219","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}
引用次数: 0
WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage. WNK1减轻氯化物外排诱导的NLRP3炎性体激活和蛛网膜下腔出血后早期脑损伤的后续神经炎症
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-27 DOI: 10.1007/s12264-025-01414-3
Panpan Zhao, Huimiao Feng, Xinyu Zhou, Jingyuan Zhou, Fangbo Hu, Taotao Hu, Yong Sun
{"title":"WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage.","authors":"Panpan Zhao, Huimiao Feng, Xinyu Zhou, Jingyuan Zhou, Fangbo Hu, Taotao Hu, Yong Sun","doi":"10.1007/s12264-025-01414-3","DOIUrl":"https://doi.org/10.1007/s12264-025-01414-3","url":null,"abstract":"<p><p>The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151222","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}
引用次数: 0
Intrinsic Functional Connectivity Associated with γ‑Aminobutyric Acid and Glutamate/Glutamine in the Lateral Prefrontal Cortex and Internalizing Psychopathology in Adolescents. 青少年前额叶外侧皮层γ -氨基丁酸和谷氨酸/谷氨酰胺相关的内在功能连接与内化精神病理。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-26 DOI: 10.1007/s12264-025-01408-1
Kai Wang, Harry R Smolker, Mark S Brown, Hannah R Snyder, Yu Cheng, Benjamin L Hankin, Marie T Banich
{"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":"https://doi.org/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":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
OGT-Mediated O-GlcNAcylation of ATF2 Protects Against Sepsis-Associated Encephalopathy by Inhibiting Microglial Pyroptosis. ogt介导的o - glcn酰化ATF2通过抑制小胶质细胞焦亡来预防败血症相关脑病。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-24 DOI: 10.1007/s12264-025-01418-z
Huan Yao, Caixia Liang, Xueting Wang, Chengwei Duan, Xiao Song, Yanxing Shang, Mingyang Zhang, Yiyun Peng, Dongmei Zhang
{"title":"OGT-Mediated O-GlcNAcylation of ATF2 Protects Against Sepsis-Associated Encephalopathy by Inhibiting Microglial Pyroptosis.","authors":"Huan Yao, Caixia Liang, Xueting Wang, Chengwei Duan, Xiao Song, Yanxing Shang, Mingyang Zhang, Yiyun Peng, Dongmei Zhang","doi":"10.1007/s12264-025-01418-z","DOIUrl":"https://doi.org/10.1007/s12264-025-01418-z","url":null,"abstract":"<p><p>Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135992","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}
引用次数: 0
The Astrocyte: A New Component of The Engram Regulates Memory Recall. 星形胶质细胞:记忆印迹的新组成部分。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-23 DOI: 10.1007/s12264-025-01409-0
Ru Li, Zilan Luo, Ding Zhong, Xia Deng, Liang Gao
{"title":"The Astrocyte: A New Component of The Engram Regulates Memory Recall.","authors":"Ru Li, Zilan Luo, Ding Zhong, Xia Deng, Liang Gao","doi":"10.1007/s12264-025-01409-0","DOIUrl":"https://doi.org/10.1007/s12264-025-01409-0","url":null,"abstract":"","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128373","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}
引用次数: 0
Triangular Wave tACS Improves Working Memory Performance by Enhancing Brain Activity in the Early Stage of Encoding. 三角波tac通过增强编码早期的大脑活动改善工作记忆表现。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-23 DOI: 10.1007/s12264-025-01413-4
Jianxu Zhang, Jian Ouyang, Tiantian Liu, Xinyue Wang, Binbin Gao, Jinyan Zhang, Manli Luo, Anshun Kang, Zilong Yan, Li Wang, Guangying Pei, Shintaro Funahashi, Jinglong Wu, Jian Zhang, Tianyi Yan
{"title":"Triangular Wave tACS Improves Working Memory Performance by Enhancing Brain Activity in the Early Stage of Encoding.","authors":"Jianxu Zhang, Jian Ouyang, Tiantian Liu, Xinyue Wang, Binbin Gao, Jinyan Zhang, Manli Luo, Anshun Kang, Zilong Yan, Li Wang, Guangying Pei, Shintaro Funahashi, Jinglong Wu, Jian Zhang, Tianyi Yan","doi":"10.1007/s12264-025-01413-4","DOIUrl":"https://doi.org/10.1007/s12264-025-01413-4","url":null,"abstract":"<p><p>Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132636","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}
引用次数: 0
Neural Tracking of Race-Related Information During Face Perception. 人脸感知过程中种族相关信息的神经跟踪。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-22 DOI: 10.1007/s12264-025-01419-y
Chenyu Pang, Na Zhou, Yiwen Deng, Yue Pu, Shihui Han
{"title":"Neural Tracking of Race-Related Information During Face Perception.","authors":"Chenyu Pang, Na Zhou, Yiwen Deng, Yue Pu, Shihui Han","doi":"10.1007/s12264-025-01419-y","DOIUrl":"https://doi.org/10.1007/s12264-025-01419-y","url":null,"abstract":"<p><p>Previous studies have identified two group-level processes, neural representations of interracial between-group difference and intraracial within-group similarity, that contribute to the racial categorization of faces. What remains unclear is how the brain tracks race-related information that varies across different faces as an individual-level neural process involved in race perception. In three studies, we recorded functional MRI signals when Chinese adults performed different tasks on morphed faces in which proportions of pixels contributing to perceived racial identity (Asian vs White) and expression (pain vs neutral) varied independently. We found that, during a pain expression judgment task, tracking other-race and same-race-related information in perceived faces recruited the ventral occipitotemporal cortices and medial prefrontal/anterior temporal cortices, respectively. However, neural tracking of race-related information tended to be weakened during explicit race judgments on perceived faces. During a donation task, the medial prefrontal activity also tracked race-related information that distinguished between two perceived faces for altruistic decision-making and encoded the Euclidean distance between the two faces that predicted decision-making speeds. Our findings revealed task-dependent neural mechanisms underlying the tracking of race-related information during face perception and altruistic decision-making.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120423","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}
引用次数: 0
Single-Nucleus Transcriptomics of the Nucleus Accumbens Reveals Cell-Type-Specific Dysregulation in Adolescent Macaques with Depressive-Like Behaviors. 伏隔核的单核转录组学揭示了具有抑郁样行为的青春期猕猴细胞类型特异性失调。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-21 DOI: 10.1007/s12264-025-01412-5
Teng Teng, Qingyuan Wu, Bangmin Yin, Jushuang Zhang, Xuemei Li, Lige Zhang, Xinyu Zhou, Peng Xie
{"title":"Single-Nucleus Transcriptomics of the Nucleus Accumbens Reveals Cell-Type-Specific Dysregulation in Adolescent Macaques with Depressive-Like Behaviors.","authors":"Teng Teng, Qingyuan Wu, Bangmin Yin, Jushuang Zhang, Xuemei Li, Lige Zhang, Xinyu Zhou, Peng Xie","doi":"10.1007/s12264-025-01412-5","DOIUrl":"https://doi.org/10.1007/s12264-025-01412-5","url":null,"abstract":"<p><p>Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features. Using single-nucleus RNA sequencing, we identified cell-specific transcriptomic changes in the nucleus accumbens (NAc), particularly in astrocytes, of adolescent macaques exhibiting depressive-like behaviors. The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques, while FKBP5 levels increased in glial cells. Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons (MSNs) and subtypes of astrocytes. Communication pathways between astrocytes and D1/D2-MSNs were also disrupted, involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4. Bulk transcriptomic and proteomic analyses corroborated these findings, and FKBP5 upregulation was confirmed by qRT-PCR, western blotting, and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress. Our results highlight the specific roles of different cell types in adolescent depression in the NAc, offering potential targets for new antidepressant therapies.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120428","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}
引用次数: 0
Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment. 海马细胞外基质蛋白层粘连蛋白β1调节神经性疼痛和疼痛相关认知障碍。
IF 5.9 2区 医学
Neuroscience bulletin Pub Date : 2025-05-21 DOI: 10.1007/s12264-025-01422-3
Ying-Chun Li, Pei-Yang Liu, Hai-Tao Li, Shuai Wang, Yun-Xin Shi, Zhen-Zhen Li, Wen-Guang Chu, Xia Li, Wan-Neng Liu, Xing-Xing Zheng, Fei Wang, Wen-Juan Han, Jie Zhang, Sheng-Xi Wu, Rou-Gang Xie, Ceng Luo
{"title":"Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.","authors":"Ying-Chun Li, Pei-Yang Liu, Hai-Tao Li, Shuai Wang, Yun-Xin Shi, Zhen-Zhen Li, Wen-Guang Chu, Xia Li, Wan-Neng Liu, Xing-Xing Zheng, Fei Wang, Wen-Juan Han, Jie Zhang, Sheng-Xi Wu, Rou-Gang Xie, Ceng Luo","doi":"10.1007/s12264-025-01422-3","DOIUrl":"https://doi.org/10.1007/s12264-025-01422-3","url":null,"abstract":"<p><p>Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca<sup>2+</sup> levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111483","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}
引用次数: 0
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