CNS Neuroscience & Therapeutics最新文献_第5页

Aerobic Exercise Training Exerts Neuroprotective Effects in Alzheimer's Disease Mice by Regulating Endoplasmic Reticulum Stress-Autophagy Pathway-Mediated Pyroptosis 有氧运动训练通过调节内质网应激自噬途径介导的焦亡对阿尔茨海默病小鼠的神经保护作用。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-17 DOI: 10.1111/cns.70620

Yunliang Wang, Xiangyun Sun, Biao He, Shaowen Yu, Yiyou Yu

Objective

This study probed into the neuroprotective effects of aerobic exercise training (AET) on Alzheimer's disease (AD) mice and further explored the molecular mechanisms through which AET regulates the endoplasmic reticulum stress (ERS)–autophagy pathway to mediate pyroptosis.

Methods

APP/PS1 mice (AD model) underwent 8 weeks of treadmill-based AET. In addition to the exercise regimen, mice were treated with intraperitoneal injections of an NLRP3 inflammasome activator, an autophagy inhibitor, an ERS inducer, and a PERK activator for assessing cognitive function and neuronal damage in the hippocampal CA1 region through cognitive assessments, histological analyses, and biochemical assays. BrdU/EdU labeling combined with NeuN and doublecortin immunostaining was used to evaluate AET-stimulated neuronal proliferation and differentiation in the hippocampus.

Results

AET improved cognitive function in AD mice. Following AET, neuronal damage in the hippocampal CA1 region was reduced, the number of Nissl bodies increased, and Aβ_1-42 and p-Tau protein levels decreased. Mechanistically, AET alleviated NLRP3 inflammasome-mediated pyroptosis and cognitive dysfunction in AD mice by inhibiting ERS and promoting autophagy in the hippocampal CA1 region. Activation of the NLRP3 inflammasome or inhibition of autophagy partially reversed the beneficial effects of AET on pyroptosis and cognitive dysfunction in AD mice. Moreover, AET reduced ERS by inhibiting the PERK-eIF2α pathway, thereby enhancing autophagy, reducing pyroptosis, and improving cognitive dysfunction.

Conclusion

AET reduces NLRP3 inflammasome-mediated pyroptosis and neuronal damage in the hippocampal CA1 region of AD mice by regulating the ERS-autophagy pathway through the inhibition of the PERK-eIF2α pathway, thereby improving cognitive function in AD mice.

目的：探讨有氧运动训练（AET）对阿尔茨海默病（AD）小鼠的神经保护作用，并进一步探讨AET通过调节内质网应激(ERS)-自噬通路介导焦亡的分子机制。方法：APP/PS1小鼠（AD模型）进行8周的跑步机AET。除了运动方案外，小鼠还通过腹腔注射NLRP3炎性体激活剂、自噬抑制剂、ERS诱导剂和PERK激活剂，通过认知评估、组织学分析和生化分析评估海马CA1区的认知功能和神经元损伤。采用BrdU/EdU标记联合NeuN和双皮质素免疫染色评价aet刺激海马神经元的增殖和分化。结果：AET改善了AD小鼠的认知功能。AET后海马CA1区神经元损伤减轻，Nissl小体数量增加，Aβ1-42和p-Tau蛋白水平降低。机制上，AET通过抑制ERS和促进海马CA1区的自噬，减轻了NLRP3炎症小体介导的AD小鼠焦亡和认知功能障碍。激活NLRP3炎性小体或抑制自噬部分逆转了AET对AD小鼠焦亡和认知功能障碍的有益作用。此外，AET通过抑制PERK-eIF2α途径降低ERS，从而增强自噬，减少焦亡，改善认知功能障碍。结论：AET通过抑制PERK-eIF2α通路调节ers自噬通路，减轻AD小鼠NLRP3炎性体介导的焦亡和海马CA1区神经元损伤，从而改善AD小鼠的认知功能。

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引用次数: 0

CXCL10 Involvement in Vestibular Migraine via the PI3K/AKT Signaling Pathway CXCL10通过PI3K/AKT信号通路参与前庭偏头痛。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-17 DOI: 10.1111/cns.70655

Mao-mei Song, Ting-yan Chen, Shi-na Song, Ying-jie Gao, Chang-xin Li, Sui-yi Xu

Aims

C-X-C motif chemokine ligand 10 (CXCL10) is a member of the CXC chemokine family, known as a classical pain-related chemokine. While CXCL10 is implicated in neuropathic pain, its role in vestibular migraine (VM) remains unclear.

Methods

Serum CXCL10 levels correlated with dizziness and headache severity in VM patients. In the rat VM model, CXCL10, C-X-C motif chemokine receptor 3 (CXCR3), and phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway expression were evaluated to explore the potential mechanisms of CXCL10 in VM.

Results

Serum CXCL10 levels in VM patients were significantly elevated and positively correlated with headache and dizziness severity. In the rat VM model, CXCL10 and CXCR3 expression in the trigeminal nucleus caudalis and vestibular nuclei were significantly increased. Additionally, molecules related to the PI3K/AKT signaling pathway and downstream inflammatory factors showed significantly elevated expression.

Conclusion

CXCL10 activates the PI3K/AKT signaling pathway, promoting the release of inflammatory factors, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, and is thus involved in the pathogenesis of VM.

目的：C-X-C基序趋化因子配体10 （CXCL10）是CXC趋化因子家族的成员，被称为经典的疼痛相关趋化因子。虽然CXCL10与神经性疼痛有关，但其在前庭偏头痛（VM）中的作用尚不清楚。方法：VM患者血清CXCL10水平与头晕、头痛严重程度相关。在大鼠VM模型中，通过CXCL10、C-X-C基元趋化因子受体3 （CXCR3）和磷脂酰肌醇4,5-二磷酸3激酶(PI3K)/蛋白激酶B （AKT）信号通路的表达，探讨CXCL10在VM中的潜在机制。结果：VM患者血清CXCL10水平显著升高，且与头痛、头晕严重程度呈正相关。在大鼠VM模型中，CXCL10和CXCR3在三叉神经尾核和前庭核中的表达显著升高。此外，PI3K/AKT信号通路相关分子及下游炎症因子表达显著升高。结论：CXCL10激活PI3K/AKT信号通路，促进白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α等炎症因子的释放，参与VM的发病过程。

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引用次数: 0

Dialogue Between the Clock Gene Bmal1 and Retinopathy: What Is the Exact Relationship? 时钟基因Bmal1与视网膜病变之间的对话：确切的关系是什么？

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-17 DOI: 10.1111/cns.70490

Yongheng Cui, Haoyan Li, Wenhui Fan, Hao Wu, Jiale Wang, Chengkang Qu, Ning Pu, Ye Tao

Background

Circadian clock coordinates the physiologic and behavioral activities with a 24-hour solar rhythm to maintain the temporal homeostasis of the body. In the mammalian retina, the circadian system regulates the physiological function of this organ. The realm of ocular circadian rhythm has earned kinds of research interest as the circadian rhythms dysfunction will disrupt the retinal homeostasis. Bmal1 functions as a major transcriptional regulator of the circadian clock.

Results

In the retina, Bmal1 mediates the processing of light information, sustains photoreceptor viability and governs neurotransmitter release. Moreover, Bmal1 gene is believed to be a pathologic cofactor of the diabetic retinopathy (DR), age-related macular degeneration (AMD), premature aging and refractive myopia. To date, the precise mechanisms underlying the pathological effects mediated by Bmal1 remain incompletely elucidated.

Conclusions

This review presents recent findings and evidence regarding the contributory role of Bmal1 in retinal degeneration and its deficits, while exploring its therapeutic potential. And th review provides a comprehensive analysis of the underlying mechanisms of the clock gene Bmal1 in other diseases, with the aim of offering insights into innovative therapeutic strategies for retinopathy.

背景：昼夜节律钟以24小时的太阳节律来协调生理和行为活动，以维持身体的时间内稳态。在哺乳动物的视网膜上，昼夜节律系统调节着这个器官的生理功能。由于昼夜节律紊乱会破坏视网膜内平衡，因此眼内昼夜节律领域引起了各种研究兴趣。Bmal1是生物钟的主要转录调节因子。结果：在视网膜中，Bmal1介导光信息的处理，维持光感受器的活力，并控制神经递质释放。此外，Bmal1基因被认为是糖尿病视网膜病变（DR）、年龄相关性黄斑变性（AMD）、早衰和屈光性近视的病理辅助因子。迄今为止，Bmal1介导的病理作用的确切机制尚未完全阐明。结论：本文综述了Bmal1在视网膜变性及其缺陷中的作用的最新发现和证据，同时探讨了其治疗潜力。此外，本综述还对时钟基因Bmal1在其他疾病中的潜在机制进行了全面分析，旨在为视网膜病变的创新治疗策略提供见解。

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引用次数: 0

Automated MRI-Based Classification of Parkinsonism: A Deep Learning Approach to Distinguish PD From PSP 基于mri的帕金森病自动分类：一种区分PD和PSP的深度学习方法。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-12 DOI: 10.1111/cns.70645

Xiaofei Hu, Zehong Cao, Tianbin Song, Ying Zhou, Weizhao Lu, Yingjie Zhu, Rui Hua, Dawei Peng, Feng Shi, Jie Lu

Objective

Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) is crucial for appropriate treatment, as each disease has distinct therapeutic requirements. The Magnetic Resonance Parkinsonism Index (MRPI) has shown promise as a diagnostic biomarker, yet manual methods introduce variability and limit its applicability. In this study, we aim to develop a fully automated algorithm for MRPI 1.0 and 2.0 calculation, and assess its ability to distinguish PD from PSP in two cohorts from different regions of China.

Methods

A total of 75 PD patients and 29 PSP patients from two hospitals were enrolled. All participants underwent neurological examinations, including the MDS-UPDRS-III and H-Y scale, as well as brain MRI scans. Additionally, tissue-intensity images derived from 3D isotropic T1WI images from 2D thick slices using a deep learning (DL)-based super-resolution (SR) technique were aligned to a standard template followed by corresponding structural mask parcellation for measurement of MRPI 1.0 and MRPI 2.0. Subsequently, a logistic regression model was constructed to identify PD patients from PSP based on these indexes.

Results

MRPI 2.0 demonstrated higher diagnostic accuracy than MRPI 1.0, with an AUC of 0.78. Additionally, the automated method showed strong linear correlations with manual assessments from an experienced radiologist, validating its reliability, and identification of PSP from PD with the average AUC of 0.85.

Conclusion

The automated MRPI method improves diagnostic accuracy for differentiating PD from PSP, providing a reliable and clinically applicable tool. The integration of a super-resolution technique to convert 2D MRI data into high-resolution images expands the potential of MRPI as a neuroimaging biomarker.

目的：区分帕金森病（PD）和进行性核上性麻痹（PSP）对于适当的治疗至关重要，因为每种疾病都有不同的治疗要求。磁共振帕金森氏症指数（MRPI）已显示出作为诊断生物标志物的希望，但手工方法引入了可变性并限制了其适用性。在本研究中，我们旨在开发一种全自动的MRPI 1.0和2.0计算算法，并评估其在中国不同地区的两个队列中区分PD和PSP的能力。方法：选取两所医院PD患者75例，PSP患者29例。所有参与者都接受了神经学检查，包括MDS-UPDRS-III和H-Y量表，以及脑部MRI扫描。此外，使用基于深度学习（DL）的超分辨率（SR）技术，从2D厚切片的3D各向同性T1WI图像中获得的组织强度图像与标准模板对齐，然后进行相应的结构掩膜分割，以测量MRPI 1.0和MRPI 2.0。随后，根据这些指标构建逻辑回归模型，从PSP中识别PD患者。结果：MRPI 2.0的诊断准确率高于MRPI 1.0， AUC为0.78。此外，自动化方法与经验丰富的放射科医生的人工评估显示出很强的线性相关性，验证了其可靠性，并且PD中PSP的识别平均AUC为0.85。结论：自动化MRPI方法提高了PD与PSP的诊断准确性，是一种可靠的临床应用工具。整合超分辨率技术将2D MRI数据转换为高分辨率图像，扩大了MRPI作为神经成像生物标志物的潜力。

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引用次数: 0

Fingolimod Exerts Therapeutic Effects on Autistic Mice via Improving the Structure and Function of Meningeal Lymphatics 芬戈莫德通过改善脑膜淋巴管的结构和功能对自闭症小鼠有治疗作用。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-11 DOI: 10.1111/cns.70649

Chen Hong, Han-Lian Xiao, Zhi-Hui Sun, Ruo-Bing Guo, Xi-Yue Zhang, Juan Ji, Xiu-Lan Sun

Background

Accumulating evidence suggests a correlation between maternal infection during pregnancy and an increased risk of autism spectrum disorder (ASD) in offspring. Our previous studies have demonstrated that maternal immune activation (MIA) induces autism-like behaviors in offspring mice, accompanied by significant lateral ventricular enlargement and cerebrospinal fluid (CSF) circulation deficits. As a critical pathway for CSF drainage, the role of meningeal lymphatic vessels in the pathophysiology of ASD remains uncharacterized. Fingolimod (FTY720), a clinically used immunomodulator, has been shown to ameliorate autism-like behaviors, but its underlying mechanism remains unclear.

Methods

We utilized an MIA-induced autism-like offspring mouse model. Autism-like behaviors in the mice were assessed using three-chamber social interaction, marble burying, grooming and other related behavioral tests. The size of the lateral ventricles was evaluated by magnetic resonance imaging and hematoxylin and eosin staining. The structure and function of meningeal lymphatic vessels were examined using immunofluorescence and in vivo visible light imaging. Lymphangiogenesis was investigated through techniques such as Western blotting, tube formation assays, sprouting experiments and other relevant methods.

Results

FTY720 not only alleviates autism-like behaviors and lateral ventricular dilation, but also significantly restores the structural integrity and drainage function of meningeal lymphatic vessels in MIA offspring. Furthermore, in vitro experiments reveal that FTY720 promotes lymphangiogenesis by targeting the S1PR3 receptor to inhibit the expression of thrombospondin-1 (TSP1), a lymphangiogenesis-related inhibitor.

Conclusion

FTY720 acts on the S1PR3 receptor to inhibit TSP1, thereby improving the structure and function of meningeal lymphatic vessels and alleviating autism-like behaviors and lateral ventricular dilation.

背景：越来越多的证据表明，怀孕期间母体感染与后代患自闭症谱系障碍（ASD）风险增加之间存在相关性。我们之前的研究表明，母体免疫激活（MIA）在后代小鼠中诱导自闭症样行为，并伴有显著的侧脑室增大和脑脊液（CSF）循环缺陷。作为脑脊液引流的重要途径，脑膜淋巴管在ASD病理生理中的作用尚未明确。Fingolimod （FTY720）是一种临床使用的免疫调节剂，已被证明可以改善自闭症样行为，但其潜在机制尚不清楚。方法：采用mia诱导的自闭症样子代小鼠模型。研究人员通过三室社会互动、弹珠掩埋、梳理和其他相关行为测试来评估小鼠的自闭症样行为。采用磁共振成像、苏木精和伊红染色评价侧脑室大小。采用免疫荧光和体内可见光显像检查脑膜淋巴管的结构和功能。通过Western blotting、成管实验、发芽实验等相关方法研究淋巴管生成。结果：FTY720不仅可以缓解自闭症样行为和侧脑室扩张，还可以显著恢复MIA子代脑膜淋巴管的结构完整性和引流功能。此外，体外实验表明，FTY720通过靶向S1PR3受体抑制淋巴管生成相关抑制剂thrombospondin-1 （TSP1）的表达，从而促进淋巴管生成。结论：FTY720作用于S1PR3受体抑制TSP1，从而改善脑膜淋巴管的结构和功能，减轻自闭症样行为和侧室扩张。

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引用次数: 0

Groundbreaking Insights Into SIRT1/NRF2-Mediated Ferroptosis Inhibition by Resveratrol in Parkinson's Disease Models 在帕金森病模型中，白藜芦醇对SIRT1/ nrf2介导的铁ptosis抑制的突破性见解

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-11 DOI: 10.1111/cns.70648

Qian Zheng, Dan Huang, Liping Zhao, Xincheng Long, Qiuxia Tu, Lingli Song, Jiaojiao Wang, Wen Zheng, Xiaojun Wen, Chunlin Zhang, Li Lei

Background

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, characterized by the degeneration of dopamine (DA) neurons in the substantia nigra (SN) of the midbrain. Recent studies have highlighted the role of ferroptosis in neuronal death, with elevated peroxide levels being a hallmark of this process. Resveratrol (RSV), a natural compound, has shown promise as a neuroprotective agent. This study explores the potential of RSV in mitigating ferroptosis in PD and elucidates its mechanisms.

Methods

Network pharmacology was employed to predict the interactions between RSV, ferroptosis, and PD-related targets. Cytoscape protein-protein interaction (PPI) analysis identified key potential targets, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses provided insights into the probable mechanisms linking RSV, ferroptosis, and PD. Subsequently, in vitro experiments were conducted to validate these findings, followed by in vivo studies to confirm the therapeutic efficacy of RSV in PD.

Results

Network pharmacology results indicated that RSV, PD and ferroptosis interact at multiple biological levels. Compared to the PD group, RSV upregulated the expression of SIRT1 and NRF2 and alleviated MPTP-induced motor deficits in mice. Furthermore, RSV reduced levels of MDA, ROS, lipid peroxidation, and cellular iron, while upregulating ferroptosis-negative regulators such as GPX4 and FTH1, as well as pathway indicators like SIRT1 and NRF2. Inhibition of SIRT1 and NRF2 resulted in a decrease in the expression of GPX4/FTH1 and the SIRT1/NRF2 signaling pathway.

Conclusions

Our findings demonstrate that RSV alleviates motor dysfunction in PD by inhibiting ferroptosis through SIRT1/NRF2 activation, providing novel mechanistic insights into its therapeutic potential for neurodegenerative diseases.

背景：帕金森病（PD）是第二常见的神经退行性疾病，以中脑黑质（SN）多巴胺（DA）神经元变性为特征。最近的研究强调了铁下垂在神经元死亡中的作用，过氧化氢水平升高是这一过程的标志。白藜芦醇（Resveratrol， RSV）是一种天然化合物，已显示出作为神经保护剂的前景。本研究探讨了RSV减轻PD患者铁下垂的潜力，并阐明了其机制。方法：采用网络药理学方法预测RSV、铁下垂和pd相关靶点之间的相互作用。细胞景观蛋白-蛋白相互作用（PPI）分析确定了关键的潜在靶点，而基因本体（GO）和京都基因与基因组百科全书（KEGG）途径富集分析则为RSV、铁死亡和PD之间的可能机制提供了见解。随后，我们进行了体外实验来验证这些发现，然后进行了体内研究来证实RSV对PD的治疗效果。结果：网络药理学结果表明，RSV、PD和铁下垂在多个生物学水平上相互作用。与PD组相比，RSV上调SIRT1和NRF2的表达，减轻mptp诱导的小鼠运动缺陷。此外，RSV降低了MDA、ROS、脂质过氧化和细胞铁的水平，同时上调了铁中毒阴性调节因子GPX4和FTH1以及SIRT1和NRF2等途径指标。SIRT1和NRF2的抑制导致GPX4/FTH1和SIRT1/NRF2信号通路的表达降低。结论：我们的研究结果表明，RSV通过SIRT1/NRF2激活抑制铁下垂，减轻PD患者的运动功能障碍，为其治疗神经退行性疾病的潜力提供了新的机制见解。

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引用次数: 0

Glymphatic System Dysfunction in Thyroid-Associated Ophthalmopathy: A Multimodal MRI Study 甲状腺相关眼病的淋巴系统功能障碍：一项多模态MRI研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-09 DOI: 10.1111/cns.70650

Lijie Zhang, Jiaqi Yao, Yiming Qi, Yongheng Luo, Jun Liu

Objective

To investigate glymphatic system (GS) alterations in thyroid-associated ophthalmopathy (TAO) patients and their links to clinical biomarkers, with the aim of understanding underlying mechanisms and potential therapeutic strategies.

Methods

This study included 28 active patients (AP), 25 inactive patients (IP) with TAO, and 37 healthy controls (HC), matched for age, sex, and educational level. Glymphatic function was evaluated using choroid plexus volume (CPV), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and coupling between global blood-oxygen-level-dependent signals and cerebrospinal fluid signals (gBOLD-CSF coupling). General linear regression analysis was conducted to explore the relationships between the GS and clinical parameters.

Results

Significant differences were found in the ALPS index between the patient groups and the HC. Both the left (ALPS_L) and right (ALPS_R) ALPS indices, as well as the average ALPS index, were significantly lower in the AP and IP groups than in the HC (p < 0.01). The overall difference across all three groups was also significant (p < 0.01). However, no significant differences were observed between the AP and IP groups. However, no significant differences in CPV were observed between either the AP or IP group and the HC. Both the AP and IP groups exhibited lower gBOLD-CSF coupling than the HC (p = 0.001; p = 0.013). Significant correlations existed between GS function and clinical parameters in both groups.

Conclusion

TAO patients demonstrate significant GS impairments linked to neuropsychological symptoms and sleep disturbances. Targeting GS function may improve quality of life in TAO patients.

目的：研究甲状腺相关性眼病（TAO）患者淋巴系统（GS）的改变及其与临床生物标志物的联系，以了解其潜在机制和潜在的治疗策略。方法：本研究纳入年龄、性别、文化程度相匹配的TAO活动期患者（AP） 28例，活动期患者（IP） 25例，健康对照（HC） 37例。通过脉络膜丛体积（CPV）、沿血管间隙扩散张量成像（DTI-ALPS）指数、全球血氧水平依赖信号与脑脊液信号耦合（gBOLD-CSF耦合）来评估淋巴功能。采用一般线性回归分析探讨GS与临床参数之间的关系。结果：患者组与HC之间的ALPS指数有显著性差异。AP组和IP组的左（ALPS_L）和右（ALPS_R）阿尔卑斯指数以及平均阿尔卑斯指数均显著低于HC组(p结论：TAO患者表现出与神经心理症状和睡眠障碍相关的显著GS损伤。针对GS功能可改善TAO患者的生活质量。

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引用次数: 0

Neuroprotective Effects of Ginsenoside Rg3 in Depressed Mice via Inhibition of the C1q Complement Pathway 人参皂苷Rg3通过抑制C1q补体通路对抑郁症小鼠的神经保护作用

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-07 DOI: 10.1111/cns.70646

Daofeng Yang, Xinran Xu, Xuerui Zhuo, Hui Cai, HaoTian Wang, Hao Liu, Yiming Sun

Aims

To explore the neuroprotective effect of Ginsenoside Rg3 in a mouse model of depression induced by chronic restraint, and to elaborate whether it exerts a protective effect by inhibiting the upregulation of complement factor C1q and related microglial cell-mediated synaptic injury.

Methods

The mouse chronic restraint model of depression was prepared from male C57BL/6 mice. The depression-like behaviors of mice were detected by sugar water preference, forced swimming test and tail suspension test. The neuronal phenotypes of mice were detected by Nissl staining, HE and Golgi staining. The expression of complement-related pathway proteins was detected by Western Blot. The corticosterone content in the peripheral blood of mice in each group was detected by corticosterone kit. Molecular simulation and MST were used to detect the binding of Rg3 and C1q. Establish a co-culture model of microglia and neurons; corticosterone stimulation and Rg3 pre-protection were given to detect the damaging effect of microglial activation on neurons and the protective effect of Rg3.

Results

In vivo experiments show that as depression progresses, the levels of complement factor C1q significantly increase, which is similar to the manifestations observed in depressed patients. Moreover, microglial cells in the hippocampus of depressed mice are significantly activated, while the number of neuronal synapses is significantly reduced, displaying apoptotic features. Ginsenoside Rg3, a drug with neuroprotective effects, reduces complement C1q levels and inhibits microglial activation, thereby protecting neurons and improving depression-like behaviors. In vitro experiments show that CORT can induce microglial cells to secrete complement factor C1q, which may trigger neuronal apoptosis. Ginsenoside Rg3 may protect HT22 neurons by regulating microglial activation, reducing the secretion of complement factors, and inhibiting neuronal apoptosis.

Conclusion

These results suggest that inhibiting excessive microglial activation and complement factor levels could be a potential strategy for treating depression.

目的探讨人参皂苷Rg3对慢性抑制抑郁小鼠模型的神经保护作用，并阐述其是否通过抑制补体因子C1q上调及相关小胶质细胞介导的突触损伤发挥保护作用。方法以雄性C57BL/6小鼠为实验对象，建立小鼠抑郁症慢性抑制模型。采用糖水偏好实验、强迫游泳实验和悬尾实验检测小鼠抑郁样行为。采用尼氏染色、HE染色和高尔基染色检测小鼠神经元表型。Western Blot检测补体相关通路蛋白的表达。采用皮质酮试剂盒检测各组小鼠外周血皮质酮含量。采用分子模拟和MST检测Rg3与C1q的结合。建立小胶质细胞与神经元共培养模型；采用皮质酮刺激和Rg3预保护，检测小胶质细胞活化对神经元的损伤作用和Rg3的保护作用。结果体内实验表明，随着抑郁症的进展，补体因子C1q水平显著升高，这与抑郁症患者的表现相似。抑郁小鼠海马小胶质细胞明显活化，神经元突触数量明显减少，呈现凋亡特征。人参皂苷Rg3是一种具有神经保护作用的药物，它可以降低补体C1q水平，抑制小胶质细胞的激活，从而保护神经元，改善抑郁样行为。体外实验表明，CORT可诱导小胶质细胞分泌补体因子C1q，而补体因子C1q可能引发神经元凋亡。人参皂苷Rg3可能通过调节小胶质细胞活化、减少补体因子分泌、抑制神经元凋亡等方式保护HT22神经元。结论抑制过度的小胶质细胞激活和补体因子水平可能是治疗抑郁症的潜在策略。

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引用次数: 0

Phox2a in Lateral Spinal Nucleus Tac1-Positive Neurons Mediates Histamine-Independent Acute Itch 脊髓外侧核tac1阳性神经元Phox2a介导组胺非依赖性急性瘙痒

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-07 DOI: 10.1111/cns.70639

Yu-Ling Chen, Zi-Ang Li, Qing-Zhen Wang, Xin-Ran Wu, E. Mao, Yao-Hua Liu, Zhi-Ping Cai, Yun-Qing Li, Zhen-Zhen Kou

Aims

While acute itch comprises histamine-dependent and -independent subtypes, critical mechanisms underlying histamine-independent itch remain poorly understood. This study investigates the role of paired-like homeobox 2a (Phox2a) in tachykinin 1-positive (Tac1⁺) neurons of the lateral spinal nucleus (LSN) as a novel target for histamine-independent pruritus intervention.

Methods

We combined chemogenetic manipulation (viral-mediated neuronal activation/inhibition), whole-cell patch-clamp recordings, immunohistochemistry, fluorescence in situ hybridization, Western blotting, and behavioral assays to investigate the role of LSN^Tac1 neurons and Phox2a in itch modulation.

Results

LSN^Tac1 neurons were specifically activated during chloroquine (CQ)–induced histamine-independent itch. Chemogenetic activation of these neurons exacerbated scratching, whereas inhibition suppressed itch behavior. Notably, Phox2a, expressed in LSN^Tac1 neurons, was downregulated during CQ-induced itch. Overexpression of Phox2a in LSN^Tac1 neurons significantly alleviated CQ-evoked scratching and was accompanied by a reduction in spontaneous excitatory postsynaptic currents (sEPSCs) amplitude without a change in sEPSCs frequency.

Conclusions

Our findings identify Phox2a in LSN^Tac1 neurons as a selective regulator of histamine-independent acute itch through presynaptic excitability. This highlights Phox2a as a novel therapeutic target for histamine-independent pruritus intervention.

虽然急性瘙痒包括组胺依赖性和非依赖性亚型，但组胺非依赖性瘙痒的关键机制仍然知之甚少。本研究探讨了配对样同源盒2a （Phox2a）在速激肽1阳性（Tac1+）外侧脊髓核（LSN）神经元中的作用，作为组胺非依赖型瘙痒干预的新靶点。方法结合化学发生操作（病毒介导的神经元激活/抑制）、全细胞膜片钳记录、免疫组织化学、荧光原位杂交、Western blotting和行为学分析，研究LSNTac1神经元和Phox2a在瘙痒调节中的作用。结果LSNTac1神经元在氯喹（chloroquine， CQ）诱导的组胺非依赖性瘙痒中被特异性激活。这些神经元的化学发生激活加剧了抓挠，而抑制则抑制了瘙痒行为。值得注意的是，在LSNTac1神经元中表达的Phox2a在cq诱导的瘙痒中被下调。在LSNTac1神经元中过表达Phox2a可显著减轻cq引起的抓痕，并伴有自发性兴奋性突触后电流（sEPSCs）振幅的降低，而sEPSCs频率没有变化。结论LSNTac1神经元中的Phox2a通过突触前兴奋性选择性调节组胺非依赖性急性瘙痒。这突出了Phox2a作为组胺非依赖性瘙痒干预的新治疗靶点。

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引用次数: 0

Acupuncture's Multisystem Neuroimmunomodulation: Central–Peripheral Interactions in Gastroenteric, Psychiatric, and Chronic Pain Disorders 针灸的多系统神经免疫调节：胃肠、精神和慢性疼痛疾病的中枢-外周相互作用。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-11-06 DOI: 10.1111/cns.70625

Lijuan Zhang, Yucai Luo, Ting Wei, Dan Wang, Zhaoxuan He, Lei Lan, Fang Zeng

Background

Acupuncture, an ancient therapeutic modality rooted in traditional Chinese medicine, has evolved into a globally recognized intervention. Mounting evidence indicates that modulation of central–peripheral interactions constitutes a key pathophysiological mechanism underlying its efficacy. This review examines how acupuncture bridges neural, immune, and endocrine systems through these dynamic interactions to address complex modern diseases.

Methods

We integrate cutting-edge advances from neuroimaging and mechanistic studies to elucidate acupuncture's mechanisms targeting central-peripheral crosstalk. Three paradigmatic conditions—functional gastrointestinal disorders, psychiatric disorders, and chronic pain—are employed to dissect its systemic effects.

Results

Acupuncture consistently demonstrates therapeutic benefits across paradigms through multisystem modulation. Core mechanisms include: neural circuitry dynamics (brain-gut/sensory axis regulation), neuro-immune-endocrine integration (cytokine-HPA-glial signaling), and humoral network modulation (hormone/metabolite-mediated cross-talk). These actions remodel complex pathophysiological networks, translating into improved clinical outcomes.

Conclusions

Acupuncture emerges as an integrative therapy with a robust scientific foundation in systems biology. Future research leveraging omics and neuroimaging should focus on developing precision protocols targeting individual genetic, epigenetic, and connectomic profiles. This evolution holds significant promise for advancing integrative neurology and expanding the application of acupuncture against complex diseases.

背景：针灸，一种根植于中国传统医学的古老治疗方式，已经发展成为一种全球公认的干预手段。越来越多的证据表明，中枢-外周相互作用的调节构成了其疗效背后的关键病理生理机制。这篇综述探讨了针灸如何通过这些动态的相互作用连接神经、免疫和内分泌系统来解决复杂的现代疾病。方法：我们结合神经影像学和机制研究的最新进展来阐明针灸针对中枢-外周串扰的机制。三种典型情况-功能性胃肠疾病，精神疾病和慢性疼痛-被用来解剖其全身影响。结果：针灸通过多系统调节，在不同的范式中始终显示出治疗效益。核心机制包括：神经回路动力学（脑-肠/感觉轴调节），神经-免疫-内分泌整合（细胞因子- hpa -胶质信号传导）和体液网络调节（激素/代谢物介导的串音）。这些行为重塑了复杂的病理生理网络，转化为改善的临床结果。结论：针灸作为一种综合疗法在系统生物学中具有坚实的科学基础。利用组学和神经影像学的未来研究应侧重于开发针对个体遗传、表观遗传和连接组谱的精确协议。这一进化为推进综合神经学和扩大针灸治疗复杂疾病的应用提供了重要的希望。

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引用次数: 0