Molecular and Cellular Neuroscience最新文献

Select NSAIDs enhance peripheral nerve growth and calcium signaling through PPARγ activation 选择性非甾体抗炎药通过激活PPARγ促进周围神经生长和钙信号传导。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-12-15 DOI: 10.1016/j.mcn.2025.104067

Jarin Tusnim , Sheetal Padhi , Karl Chelala , J. Patrick O'Connor , Bryan J. Pfister , Bonnie L. Firestein , Jonathan M. Grasman

Peripheral nerve injuries (PNIs) are a significant health concern, affecting millions of individuals and result in debilitating sensory and motor deficits, as well as severe neuropathic pain. Treatment of PNIs depend on severity and gap length, with small gaps repaired by sutures and larger ones requiring autologous nerve grafting, the gold standard for bridging defects. However, autologous grafting also has significant limitations, including low recovery rates and complications such as neuroma formation. Tissue engineering and regenerative medicine offer promising alternatives but lack effective treatments directly enhancing nerve regeneration. Our previous research explored the potential of repurposing non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen and indomethacin, to promote peripheral nerve regeneration (PNR). These drugs demonstrated enhanced axonal growth and calcium signaling, suggesting a dual role in promoting neuronal recovery. The present study aimed to identify the underlying mechanism of this drug-mediated axonal growth. We hypothesized that ibuprofen and indomethacin function as peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibiting RhoA activation and thus facilitating axonal growth. To test this, we performed immunostaining, Western blotting, and calcium imaging on dorsal root ganglion (DRG) explants treated with these drugs, both with and without PPARγ antagonists. We also investigated whether cyclooxygenase (COX) inhibition, the primary pain-relieving mechanism of NSAIDs, contributes to axonal growth. Our findings indicate that ibuprofen and indomethacin promote axonal growth through PPARγ activation, independent of COX inhibition, suggesting that targeting the PPARγ pathway could be a novel therapeutic strategy for enhancing nerve regeneration and improving outcomes for patients with PNIs.

周围神经损伤（PNIs）是一个重要的健康问题，影响到数百万人，导致衰弱的感觉和运动缺陷，以及严重的神经性疼痛。PNIs的治疗取决于严重程度和间隙长度，小的间隙通过缝合修复，大的需要自体神经移植，这是桥接缺陷的金标准。然而，自体移植也有明显的局限性，包括低恢复率和并发症，如神经瘤的形成。组织工程和再生医学提供了有希望的替代方法，但缺乏直接增强神经再生的有效治疗方法。我们之前的研究探索了非甾体抗炎药（NSAIDs）、布洛芬和吲哚美辛促进周围神经再生（PNR）的潜力。这些药物显示了轴突生长和钙信号的增强，表明它们在促进神经元恢复方面具有双重作用。本研究旨在确定这些药物介导的轴突生长的潜在机制。我们假设布洛芬和吲哚美辛作为过氧化物酶体增殖物激活受体γ (PPARγ)激动剂，抑制RhoA激活，从而促进轴突生长。为了验证这一点，我们对用这些药物治疗的背根神经节（DRG）外植体进行了免疫染色、Western blotting和钙成像，无论是否使用PPARγ拮抗剂。我们还研究了环氧化酶（COX）抑制是否有助于轴突生长，COX是非甾体抗炎药的主要镇痛机制。我们的研究结果表明，布洛芬和吲哚美辛通过PPARγ激活促进轴突生长，独立于COX抑制，这表明靶向PPARγ途径可能是一种新的治疗策略，可以增强PNIs患者的神经再生和改善预后。

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引用次数: 0

Agrimonolide exhibits anti-neuroinflammatory potential via TLR4-mediated pathways 农单内酯通过tlr4介导的途径显示出抗神经炎症的潜力。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-12-01 DOI: 10.1016/j.mcn.2025.104057

Weiling Li , Qian Peng , Ping Sun , Lingyi Xiang , Yangxin Qi , Xiansheng Ye , Yingying Shi , Song Hu , Haifeng Chen , Binlian Sun

Microglial and astrocytic activation is the main reason for the neuroinflammatory responses, which damages neurons resulting in neurological disorders. Currently, there are few drugs that directly target neuroinflammation in clinical practice, which highlights the urgent need for effective inhibitors. In this study, we identified agrimonolide, from a screen of 40 compounds, as an inhibitor of glia activation, and further confirmed its efficacy in vitro and in vivo. In cellular models, agrimonolide significantly reduced the expression levels of proinflammatory cytokines (IL-1β, IL-6 and TNFα) in LPS stimulated BV2 cells and primary astrocytes. Mechanistic investigation revealed that agrimonolide suppresses the activation of both NF-κB and MAPK signaling pathways, combined the molecular docking results, it is suggested that agrimonolide may have multiple targets. In ICR mice, our measurements showed that agrimonolide treatment decreased LPS-induced glial activation, as evidenced by the protein levels of IBA-1 and GFAP. Additionally, it significantly inhibited the activation of TLR4-mediated signaling pathways. Our findings suggest that agrimonolide suppresses neuroinflammatory responses by inhibiting microglial and astrocytic activation, providing insight into potential treatment strategies for neuroinflammation-related diseases.

小胶质细胞和星形胶质细胞的激活是神经炎症反应的主要原因，神经炎症反应损害神经元，导致神经系统疾病。目前，临床实践中直接针对神经炎症的药物很少，因此迫切需要有效的抑制剂。在本研究中，我们从40种化合物中筛选出了agrimonolide作为神经胶质细胞激活抑制剂，并进一步证实了其体外和体内的有效性。在细胞模型中，农素内酯显著降低LPS刺激的BV2小胶质细胞和原代星形胶质细胞中促炎因子（IL-1β、IL-6和TNFα）的表达水平。机制研究表明，农单内酯可抑制NF-κB和MAPK信号通路的激活，结合分子对接结果，提示农单内酯可能具有多靶点。在ICR小鼠中，我们的测量结果表明，农素内酯处理降低了lps诱导的胶质细胞激活，IBA-1和GFAP的蛋白水平证明了这一点。此外，它还能显著抑制tlr4介导的信号通路的激活。我们的研究结果表明，农单内酯通过抑制小胶质细胞和星形胶质细胞的激活来抑制神经炎症反应，为神经炎症相关疾病的潜在治疗策略提供了见解。

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引用次数: 0

haFGF14–154 attenuates Aβ1–42-induced neurotoxicity by facilitating BDNF maturation in a neuron-astrocyte co-culture system 在神经元-星形胶质细胞共培养系统中，haFGF14-154通过促进BDNF成熟来减弱a β1-42诱导的神经毒性。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-11-17 DOI: 10.1016/j.mcn.2025.104056

Dong Peng , Luyi Wu , Lei Zhang , Hongxia Chen , Bo Hu , Qihao Zhang , Yadong Huang

haFGF₁₄_–₁₅₄ improves cognitive impairment in animal models of Alzheimer's disease (AD), but the effects and mechanisms of astrocytes on the neuroprotection mediated by haFGF₁₄_–₁₅₄ remain unclear. Here, a neuron-astrocyte co-culture system was established to investigate the functions of astrocytes. The results showed that astrocytes strengthened the protective effect of haFGF₁₄_–₁₅₄ on Aβ₁_–₄₂-treated neurons. This enhanced protective function of haFGF₁₄_–₁₅₄ correlates with phenotypic transition in astrocytes, as demonstrated by the suppression of Aβ₁_–₄₂-induced A1-like genes and the elevation of A2-like markers in vitro. These observations are consistent with the reduction of GFAP and C3 levels in the hippocampus and prefrontal cortex of APP/PS1 mice treated with haFGF₁₄_–₁₅₄. haFGF₁₄_–₁₅₄ modified the function of astrocytes by activating the AKT/CREB/BDNF pathway, thereby promoting neurite growth. Moreover, haFGF₁₄_–₁₅₄ up-regulated the expression of Furin and MMP9 in astrocytes, leading to the processing of pro-BDNF. This effect was replicated in APP/PS1 mice administered with haFGF₁₄_–₁₅₄. Compared to the Aβ group, the BDNF level in the co-culture system supernatant was increased, while the IL-1β level was decreased following haFGF₁₄_–₁₅₄ treatment. Additionally, haFGF₁₄_–₁₅₄ inhibited neuronal apoptosis in the co-culture system, as evidenced by a decrease in pro-BDNF/P75^NTR, an increase in Bcl-2, and a reduction of Bad and Cleaved-caspase-3. In conclusion, current results demonstrate that astrocytes are crucial for mediating the protective effect of haFGF₁₄_–₁₅₄ against neuronal damage, and underline the importance of the AKT/CREB/BDNF pathway in promoting neurite growth and attenuating neuronal apoptosis.

haFGF14-154改善阿尔茨海默病（AD）动物模型的认知障碍，但星形胶质细胞对haFGF14-154介导的神经保护的作用和机制尚不清楚。本实验建立神经元-星形胶质细胞共培养系统，研究星形胶质细胞的功能。结果表明，星形胶质细胞增强了haFGF14-154对a β1-42处理的神经元的保护作用。haFGF14-154的这种增强的保护功能与星形胶质细胞的表型转变有关，这一点在体外被a β1-42诱导的a1样基因的抑制和a2样标记物的升高所证明。这些观察结果与haFGF14-154治疗APP/PS1小鼠海马和前额叶皮层GFAP和C3水平的降低一致。haFGF14-154通过激活AKT/CREB/BDNF通路修饰星形胶质细胞的功能，从而促进神经突生长。此外，haFGF14-154上调星形胶质细胞中Furin和MMP9的表达，导致pro-BDNF的加工。haFGF14-154在APP/PS1小鼠中也得到了同样的效果。与Aβ组相比，haFGF14-154处理后，共培养系统上清液中BDNF水平升高，IL-1β水平降低。此外，haFGF14-154抑制共培养系统中的神经元凋亡，这可以通过降低pro-BDNF/P75NTR，增加Bcl-2，减少Bad和Cleaved-caspase-3来证明。总之，目前的研究结果表明星形胶质细胞在介导haFGF14-154对神经元损伤的保护作用中起着至关重要的作用，并强调了AKT/CREB/BDNF通路在促进神经突生长和减轻神经元凋亡中的重要性。

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引用次数: 0

Decoding aging through nitrogen containing compounds: A nutrigenomic insight 通过含氮化合物解码衰老：营养基因组学见解

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-11-13 DOI: 10.1016/j.mcn.2025.104055

Spandana Rajendra Kopalli , Nitu L. Wankhede , Sushruta Koppula , Brijesh Taksande , Aman B. Upaganlawar , Arifullah Mohammed , Milind Umekar , Mayur B. Kale

Nitrogen compounds are increasingly recognized as key modulators in nutrigenomics, with profound implications for understanding and influencing the aging process. Traditionally central to human nutrition, these compounds are now understood to play critical roles in regulating gene expression, cellular signalling, and metabolic pathways that are essential for maintaining health during aging. Nitrogen-containing molecules, such as amino acids, polyamines, and nitric oxide, contribute to vital processes including protein synthesis, mitochondrial function, and oxidative stress management. These mechanisms are crucial for cellular homeostasis but become increasingly vulnerable to disruption during aging, leading to tissue degeneration and heightened susceptibility to age-related diseases. Disruptions in nitrogen metabolism can impair proteostasis, mitochondrial bioenergetics, and antioxidant defences, accelerating cellular decline. Recent research has expanded our understanding of how nitrogen compounds interact with nutrient-sensing pathways such as mTOR and AMPK, as well as epigenetic regulators that influence DNA repair, autophagy, and inflammation. These findings highlight the therapeutic potential of optimizing nitrogen metabolism to enhance health span and mitigate the effects of aging. The emerging field of nitrogen nutrigenomics offers promising opportunities for developing targeted nutritional strategies aimed at improving quality of life and delaying age-related decline. By integrating historical perspectives with contemporary discoveries, this review underscores the complex interplay between nitrogen compounds and aging while inspiring future research into innovative interventions that harness their benefits for longevity and well-being. Ultimately, optimizing nitrogen metabolism could pave the way for new approaches to extending health span and addressing age-related health challenges.

氮化合物越来越被认为是营养基因组学中的关键调节剂，对理解和影响衰老过程具有深远的意义。传统上，这些化合物是人类营养的核心，现在人们了解到，这些化合物在调节基因表达、细胞信号传导和代谢途径方面发挥着关键作用，这些途径对于在衰老过程中保持健康至关重要。含氮分子，如氨基酸、多胺和一氧化氮，有助于蛋白质合成、线粒体功能和氧化应激管理等重要过程。这些机制对细胞稳态至关重要，但在衰老过程中越来越容易受到破坏，导致组织变性和对年龄相关疾病的易感性增加。氮代谢的中断会损害蛋白质平衡、线粒体生物能量学和抗氧化防御，加速细胞衰退。最近的研究扩大了我们对氮化合物如何与营养感应途径（如mTOR和AMPK）以及影响DNA修复、自噬和炎症的表观遗传调节因子相互作用的理解。这些发现突出了优化氮代谢以延长健康寿命和减轻衰老影响的治疗潜力。新兴的氮营养基因组学领域为制定有针对性的营养策略提供了有希望的机会，旨在提高生活质量和延缓与年龄相关的衰退。通过将历史观点与当代发现相结合，本综述强调了氮化合物与衰老之间复杂的相互作用，同时启发了未来对利用氮化合物对长寿和健康有益的创新干预措施的研究。最终，优化氮代谢可以为延长健康寿命和解决与年龄相关的健康挑战的新方法铺平道路。

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引用次数: 0

The role of polarization dynamics in macrophages and microglia on the inflammatory microenvironment of spinal cord injury 巨噬细胞和小胶质细胞极化动力学在脊髓损伤炎症微环境中的作用。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-11-06 DOI: 10.1016/j.mcn.2025.104054

Yue Hu, Jun Gao

Spinal cord injury (SCI) triggers complex pathological processes—including neuroinflammation, glial scar formation, and impaired neuronal regeneration—that hinder recovery. Macrophages and microglia centrally regulate these processes through dynamic polarization states across a spectrum of pro−/anti-inflammatory phenotypes. While single-cell technologies reveal glial and immune heterogeneity and interactions in the SCI microenvironment, translating these insights into immunomodulatory therapies remains challenging. This review therefore examines mechanisms driving macrophage/microglia polarization in the microenvironment of SCI, focusing on their therapeutic targeting potential.

脊髓损伤（SCI）引发复杂的病理过程，包括神经炎症、神经胶质瘢痕形成和神经元再生受损，这些都会阻碍康复。巨噬细胞和小胶质细胞通过动态极化状态集中调节这些过程。虽然单细胞技术揭示了脊髓损伤微环境中神经胶质和免疫的异质性和相互作用，但将这些见解转化为免疫调节疗法仍然具有挑战性。因此，本综述探讨了在脊髓损伤微环境中驱动巨噬细胞/小胶质细胞极化的机制，重点研究了它们的治疗靶向潜力。

引用次数: 0

Glymphatic impairment in Moyamoya disease 烟雾病的淋巴损害。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-11-04 DOI: 10.1016/j.mcn.2025.104053

Yao Chen , Xichang Liu

Moyamoya disease (MMD) is a chronic disease characterized by the progressive narrowing of the terminal internal carotid artery, accompanied by abnormal angiogenesis at the base of the skull and defective formation of the vascular network, with a complex clinical picture and a risk of cognitive impairment and dementia in addition to ischemic and hemorrhagic events. The glymphatic system is a cerebrospinal fluid and interstitial fluid drainage pathway that acts throughout the brain to remove metabolic wastes from the brain parenchyma. Clinical studies have found that cognitive decline in patients with MMD is linked to metabolite accumulation and reduced diffusion tensor image analysis along the perivascular space (DTI-ALPS), highlighting the potential impact of glymphatic system impairment. This dysfunction may stem from a combination of chronic hypoperfusion, systemic microstructural damage and inflammatory response, and is an important link to further deterioration of vascular cognitive function. This article discusses the recent findings on glymphatic system disorders in MMD, with the objective of providing new approaches to the disease.

烟雾病（Moyamoya disease， MMD）是一种慢性疾病，以颈内动脉终末进行性狭窄为特征，伴有颅底血管生成异常和血管网络形成缺陷，临床表现复杂，除了缺血性和出血事件外，还存在认知障碍和痴呆的风险。淋巴系统是脑脊液和间质液的引流途径，作用于整个大脑，从脑实质中清除代谢废物。临床研究发现，烟雾病患者的认知能力下降与代谢物积累和沿血管周围间隙弥散张量图像分析（DTI-ALPS）减少有关，突出了淋巴系统损伤的潜在影响。这种功能障碍可能源于慢性灌注不足、全身微结构损伤和炎症反应的共同作用，是血管认知功能进一步恶化的重要环节。本文讨论了烟雾病中淋巴系统疾病的最新发现，目的是提供新的治疗方法。

引用次数: 0

Bridging the gap in the management of Alzheimer's disease using fecal microbiota transplantation 利用粪便微生物群移植弥合阿尔茨海默病管理方面的差距。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-11-01 DOI: 10.1016/j.mcn.2025.104052

Bushra Bashir , Monica Gulati , Sukriti Vishwas , Md Sadique Hussain , Gaurav Gupta , Puneet Kumar , Poonam Negi , Neeraj Mittal , Kamal Dua , Sachin Kumar Singh

Alzheimer's disease (AD) is a neurodegenerative disease that greatly impairs the health status of human beings and creates significant burdens on individuals, families, and society. AD is characterized by the buildup of pathological proteins and glial cell dysregulated activity. Additional hallmark features include oxidative stress, neuroinflammation, impaired autophagy, cellular senescence, mitochondrial dysfunction, epigenetic alterations, reduced neurogenesis, increased blood-brain barrier permeability, and age-inappropriate intestinal dysbiosis. There is significant evidence that shows that microbiota in the gut affects the development and progression of AD. As a result, gut microbiota modulation has been identified as a new method of clinical management of AD, and more and more efforts have been devoted to identifying new methodologies for its prevention and treatment. This paper will discuss the role of gut microbiome in the etiopathogenesis of AD and consider the possibilities of fecal microbiota extract (FME) supplementation, commonly referred to as fecal microbiota transplantation (FMT). It is both a prophylactic and curative approach. The FMT therapy is grounded on the premise that anti-inflammatory effects, modifications of amyloid β, improved synaptic plasticity, short-chain fatty acids, and histone acetylation are the principles behind the enhancement of AD. The current review will present an overview of the linkage between FMT and AD as well. It further examines and evaluates the effects of FMT on aging-based mechanisms that support the development of AD. It also provides a broad description of the recent clinical and preclinical evidence on the application of FMT to AD.

阿尔茨海默病（Alzheimer's disease， AD）是一种严重损害人类健康的神经退行性疾病，给个人、家庭和社会造成了巨大的负担。AD的特点是病理蛋白的积累和神经胶质细胞活性失调。其他标志性特征包括氧化应激、神经炎症、自噬受损、细胞衰老、线粒体功能障碍、表观遗传改变、神经发生减少、血脑屏障通透性增加和与年龄不适应的肠道生态失调。有重要证据表明，肠道微生物群影响阿尔茨海默病的发生和进展。因此，调节肠道菌群已被确定为阿尔茨海默病临床管理的新方法，并且越来越多的人致力于寻找预防和治疗阿尔茨海默病的新方法。本文将讨论肠道微生物群在AD发病机制中的作用，并考虑补充粪便微生物群提取物（FME）的可能性，通常称为粪便微生物群移植（FMT）。它既是一种预防方法，也是一种治疗方法。FMT治疗的前提是抗炎作用、β淀粉样蛋白修饰、突触可塑性改善、短链脂肪酸和组蛋白乙酰化是阿尔茨海默病增强背后的原理。本综述也将概述FMT和AD之间的联系。它进一步检查和评估FMT对支持AD发展的基于衰老的机制的影响。它还提供了关于FMT应用于AD的近期临床和临床前证据的广泛描述。

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引用次数: 0

The LINC00094/miR-19a-3p signalling regulates glycolysis and mediates cold induced traumatic brain injury LINC00094/miR-19a-3p信号调节糖酵解并介导冷诱导的创伤性脑损伤。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-10-10 DOI: 10.1016/j.mcn.2025.104050

Divya Mishra , Rashi Saxena , Deepak , Rekha Yadav , Durga Prasad Mishra

Cold induced traumatic brain injury (Ci-TBI), is a lethal and highly debilitating neurodegenerative condition with limited therapeutic options. Metabolic perturbations like deregulated glycolysis is perceived as a hallmark of TBIs including Ci-TBIs. Elucidation of the underlying mechanisms regulating Ci-TBI are essential devising effective therapeutic strategies. In the present study, induction of Ci-TBI in-vitro and in a mice model down regulated the long noncoding RNA LINC00094. Our mechanistic studies revealed that LINC00094 targeted and inhibited miR-19a-3p both in the neuronal culture based in vitro model of Ci-TBI vitro and a Ci-TBI mice model in vivo. The elevated expression of miR-19a-3p further targeted and inhibited the adiponectin receptor 2 (AdipoR2) and repressed glycolysis, glucose uptake and lactate production. Collectively, our results elucidated the molecular cascade and underscored the significance of the LINC00094/miR-19a-3p signalling in regulation of glycolysis mediating Ci-TBI. These novel findings indicate that LINC00094 and miR-19a-3p could be of prognostic and diagnostic value as potential biomarkers of Ci-TBI progression.

冷致创伤性脑损伤（Ci-TBI）是一种致命且高度衰弱的神经退行性疾病，治疗选择有限。代谢紊乱如糖酵解失调被认为是包括ci - tbi在内的tbi的标志。阐明调节Ci-TBI的潜在机制是制定有效治疗策略的必要条件。在本研究中，体外和小鼠模型诱导Ci-TBI下调长链非编码RNA LINC00094。我们的机制研究表明，LINC00094在体外培养的Ci-TBI模型和体内Ci-TBI小鼠模型中都能靶向并抑制miR-19a-3p。miR-19a-3p的表达升高进一步靶向并抑制脂联素受体2 (AdipoR2)，抑制糖酵解、葡萄糖摄取和乳酸生成。总的来说，我们的结果阐明了分子级联，并强调了LINC00094/miR-19a-3p信号传导在糖酵解介导的Ci-TBI调控中的重要性。这些新发现表明，LINC00094和miR-19a-3p可能作为Ci-TBI进展的潜在生物标志物具有预后和诊断价值。

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引用次数: 0

AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles AstroGreen转基因小鼠阐明了星形胶质细胞衍生的细胞外囊泡的运输。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-10-08 DOI: 10.1016/j.mcn.2025.104051

Lisa Nieland , Edwina Abou Haidar , David Rufino-Ramos , Shilpa Prabhakar , Youssef Samaha , Koen Breyne , Francis K. Fordjour , Saumya Das , Marike L.D. Broekman , Stephen Gould , Xandra O. Breakefield , Erik R. Abels

Astrocytes interact with neighboring cells by releasing extracellular vesicles (EVs). Tools to study astrocyte EV-mediated communication with other brain cells in vivo are essential. In this study, we crossed the Exomap1 transgenic mouse expressing Cre-activated human-specific CD81 (HsCD81) fused to the fluorescent protein mNeonGreen (HsCD81mNG), to a transgenic mouse expressing Cre under the astrocyte-expressing GFAP promoter resulting in Exomap1::Gfap-Cre mice, referred to here as AstroGreen. We characterized HsCD81mNG-expressing astrocytes and shedded EVs loaded with HsCD81mNG and Cre, both in vitro and in mouse brains. Using this model, we show that HsCD81mNG can be used to track EV content, production, and functional Cre transfer in vitro and in the brain, allowing evaluation of the interaction of astrocytes with neighboring cells mediated by EVs. We anticipate that this model will improve our understanding of astrocytes transferring EVs within their surroundings during normal physiological processes and in the context of neuropathological conditions.

星形胶质细胞通过释放细胞外囊泡（EVs）与邻近细胞相互作用。在体内研究星形胶质细胞ev介导的与其他脑细胞的通讯工具是必不可少的。在本研究中，我们将表达crea激活的人类特异性CD81 （HsCD81）与荧光蛋白mNeonGreen （HsCD81mNG）融合的Exomap1转基因小鼠与在星形胶质细胞表达GFAP启动子下表达Cre的转基因小鼠杂交，得到Exomap1:: GFAP -Cre小鼠，这里简称AstroGreen。我们在体外和小鼠脑内对表达HsCD81mNG的星形胶质细胞和装载HsCD81mNG和Cre的脱落的EVs进行了表征。通过该模型，我们发现HsCD81mNG可用于在体外和脑内跟踪EV含量、产生和功能Cre转移，从而评估EV介导的星形胶质细胞与邻近细胞的相互作用。我们预计该模型将提高我们对星形胶质细胞在正常生理过程和神经病理条件下在其周围环境中转移ev的理解。

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引用次数: 0

Exosome-based therapeutic approach for spinal cord injury: A review 基于外泌体的脊髓损伤治疗方法综述。

IF 2.4 3区医学 Q3 NEUROSCIENCES

Molecular and Cellular Neuroscience

Pub Date : 2025-09-25 DOI: 10.1016/j.mcn.2025.104048

Shuai Bai , Rong Rong Qiang , Rui Yang Liu , De Jie Kang , Yan Ling Yang

Spinal cord injury (SCI) is a devastating neurological condition associated with high rates of disability and mortality, placing substantial burdens on patients, families, and healthcare systems. Current treatment strategies, including surgical decompression, pharmacological intervention, and rehabilitation, offer only limited functional recovery. Exosomes, extracellular vesicles with a double-membrane structure, range in diameter from 30 to 150 nm and play a key role in intercellular communication by transporting proteins, lipids, and nucleic acids. Recent studies have highlighted their potential as natural nanocarriers for the treatment of neurodegenerative disorders. Due to their low immunogenicity and multifunctional reparative properties, exosomes have shown considerable efficacy in promoting neurological recovery following SCI. They exert therapeutic effects through multiple mechanisms, including modulation of the inflammatory response, promoting axonal regeneration and angiogenesis, and inhibiting apoptosis. This review summarizes the pathophysiological mechanisms underlying SCI and elucidates the therapeutic roles of exosomes and exosomal microRNAs (exo-miR) in SCI repair. Furthermore, it discusses current challenges and prospects for the clinical translation of exosome-based therapies, aiming to provide valuable insights for future research and clinical applications.

脊髓损伤（SCI）是一种具有高致残率和高死亡率的破坏性神经系统疾病，给患者、家庭和医疗保健系统带来了沉重的负担。目前的治疗策略，包括手术减压、药物干预和康复，只能提供有限的功能恢复。外泌体是具有双膜结构的细胞外囊泡，直径从30到150 nm （nm）不等，通过运输蛋白质、脂质和核酸在细胞间通讯中起关键作用。最近的研究强调了它们作为治疗神经退行性疾病的天然纳米载体的潜力。由于其低免疫原性和多功能修复特性，外泌体在促进脊髓损伤后神经恢复方面显示出相当大的功效。它们通过多种机制发挥治疗作用，包括调节炎症反应、促进轴突再生和血管生成、抑制细胞凋亡。本文综述了脊髓损伤的病理生理机制，并阐明了外泌体和外泌体microRNAs （exo-miR）在脊髓损伤修复中的治疗作用。此外，本文还讨论了目前基于外泌体疗法的临床翻译面临的挑战和前景，旨在为未来的研究和临床应用提供有价值的见解。

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引用次数: 0