Neuroscience Letters最新文献_第6页

Alcohol-induced neuropathy associated downregulation of Kv7 channels in primary nociceptors 酒精诱导的神经病变与初级伤害感受器中Kv7通道的下调有关。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-19 DOI: 10.1016/j.neulet.2025.138461

Feyza Alyu Altinok , Ilhem Dallali , Ahmed Hasan , Abderaouf Boubekka , Elif Kaya Tilki , Yusuf Ozturk

Chronic alcohol consumption is a well-known risk factor for peripheral neuropathy, often presenting with thermal hyperalgesia and mechanical allodynia. While the involvement of dorsal root ganglia (DRG) neurons in alcohol-induced neuropathy (AIN) is recognized, the molecular mechanisms—particularly the role of Kv7-KCNQ potassium channel remains insufficiently understood. This research focused on evaluating the impact ofchronic alcohol exposure on Kv7 channel function and gene expression in DRG neurons, focusing on the KCNQ2 and KCNQ5 subunits.A rat model of AIN was established via oral gavage administration of 35 % ethanol (10 g/kg, twice daily) for 10 weeks. Pain hypersensitivity was evaluated using the electronic von Frey and Hargreaves tests. Quantitative real-time PCR was used to evaluate the mRNA expression of KCNQ2 and KCNQ5 channels. M−current (IM) density and neuronal excitability were assessed through whole-cell voltage-clamp and current-clamp recordings, respectively.Chronic ethanol exposure significantly reduced both mechanical and thermal thresholds, confirming the development of neuropathic pain. We observed a marked downregulation in the mRNA expression of KCNQ2 and KCNQ5 subunits, accompanied by a diminished M−current density within DRG neurons. These alterations were linked to increased neuronal excitability and heightened pain sensitivity in rats exposed to ethanol.These findings demonstrate that AIN is marked by a significant downregulation of KCNQ2 and KCNQ5 channel expression and function, contributing to elevated neuronal excitability and the onset of thermal hyperalgesia and mechanical allodynia. The suppressed activity of KCNQ/M channels within DRG neurons of AIN rats highlights Kv7 channels as promising molecular targets for AIN therapy.

慢性饮酒是周围神经病变的一个众所周知的危险因素，通常表现为热痛觉过敏和机械异常性痛。虽然已经认识到背根神经节（DRG）神经元参与酒精性神经病变（AIN），但其分子机制，特别是Kv7-KCNQ钾通道的作用仍未得到充分的了解。本研究的重点是评估慢性酒精暴露对DRG神经元中Kv7通道功能和基因表达的影响，重点是KCNQ2和KCNQ5亚基。采用35 %乙醇（10 g/kg，每日2次）灌胃建立AIN大鼠模型，持续10 周。采用电子von Frey和Hargreaves试验评估疼痛超敏反应。采用实时荧光定量PCR检测KCNQ2和KCNQ5通道mRNA表达情况。分别通过全细胞电压钳和电流钳记录m电流（IM）密度和神经元兴奋性。慢性乙醇暴露显著降低机械和热阈值，证实神经性疼痛的发展。我们观察到KCNQ2和KCNQ5亚基的mRNA表达明显下调，同时DRG神经元内的m电流密度降低。这些变化与暴露于乙醇的大鼠的神经元兴奋性增加和疼痛敏感性增强有关。这些发现表明，AIN以KCNQ2和KCNQ5通道的表达和功能显著下调为标志，有助于神经元兴奋性升高和热痛觉过敏和机械异常性疼痛的发生。AIN大鼠DRG神经元中KCNQ/M通道活性的抑制表明Kv7通道是AIN治疗的有希望的分子靶点。

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引用次数: 0

Involvement of substance P/NK1 receptor system in central sensitization in chronic pain P/NK1受体系统参与慢性疼痛的中枢致敏。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-22 DOI: 10.1016/j.neulet.2025.138464

Juan Chen , Yimin Lai , Wei Li

Chronic pain has become a serious health issue, affecting more than 30% of people worldwide. One of the main mechanisms of chronic pain is central sensitization. It is well known that substance P (SP) and its receptor, Neurokinin 1 receptor (NK1R), play an important role in transmission of nociceptive signals. However, whether SP/NK1R system is involved in central sensitization in chronic pain remains controversial. In the present study, we adopted spared nerve injury (SNI) mouse model to induce neuropathic pain and assessed the role of SP/NK1R system in the development of hyperalgesia and central sensitization. We observed that hyperalgesia occurred in non-injured body part of SNI mice in tail withdrawal test. We also demonstrated hyperexcitability of S1 apical dendrites in SNI mice. Notably, the hyperalgesia behavior and hyperactivity of S1 apical dendrites were alleviated by NK1R antagonist L-703606. These results indicate that SP/NK1R system is involved in central sensitization in chronic pain.

慢性疼痛已成为一个严重的健康问题，影响着全世界30%以上的人。慢性疼痛的主要机制之一是中枢致敏。众所周知，P物质（SP）及其受体神经激肽1受体（Neurokinin 1 receptor, NK1R）在痛觉信号的传递中起着重要作用。然而，SP/NK1R系统是否参与慢性疼痛的中枢致敏仍然存在争议。本研究采用余留神经损伤（SNI）小鼠模型诱导神经性疼痛，评估SP/NK1R系统在痛觉过敏和中枢致敏发展中的作用。我们在脱尾实验中观察到SNI小鼠非损伤部位出现痛觉过敏。我们也证实了SNI小鼠S1顶端树突的高兴奋性。值得注意的是，NK1R拮抗剂L-703606可减轻S1尖树突的痛觉过敏行为和亢进。这些结果表明SP/NK1R系统参与了慢性疼痛的中枢致敏。

引用次数: 0

Short-term immobilization impairs pointing direction programming and early motor control processes 短期固定化损害指向编程和早期运动控制过程。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-11 DOI: 10.1016/j.neulet.2025.138446

C.R. Scotto, F.R. Danion, Y. Blandin, L. Toussaint

Short-term limb immobilization is a valuable method for studying the contribution of proprioception since it temporarily reduces sensory and motor inputs. While several studies have shown that immobilization impairs cognitive and sensorimotor processes, none have yet demonstrated how it could specifically impact the programming of movement direction. Here, participants (N = 32) made uncorrected pointing movements toward five visual targets located in different directions − but requiring constant amplitude − without benefiting from any visual feedback on the hand. Pointing was performed on two consecutive days by Control and Immobilized participants, the latter of whom had worn a splint on the right arm during this 24 h period. Results showed that immobilization increased the duration of movement planning (i.e., longer reaction time) necessary to specify hand-path direction. A greater counterclockwise directional bias was observed at peak acceleration in the Immobilized group and persisted until the uncorrected movement offset. These results suggest that immobilization impacts direction programming as well as early motor control processes. We argue that proprioception deprivation impairs the perception of limb position, leading to both slower and less accurate motor command selection. Overall, we interpret that the lack of proprioceptive feedback and efference copies may influence the accuracy of movement planning after 24 h of immobilization, possibly reflecting changes in processes related to internal model mechanisms.

短期肢体固定是研究本体感觉贡献的一种有价值的方法，因为它暂时减少了感觉和运动输入。虽然有几项研究表明，不动会损害认知和感觉运动过程，但还没有研究表明它是如何具体影响运动方向的编程的。在这里，参与者（N = 32）对位于不同方向的五个视觉目标进行了未经纠正的指向运动-但需要恒定的振幅-没有从任何手部视觉反馈中受益。连续两天由对照组和固定组的参与者进行指指，后者在这24小时内在右臂上佩戴夹板。结果表明，固定化增加了指定手路方向所需的运动规划时间（即更长的反应时间）。在固定组中，在峰值加速度时观察到更大的逆时针方向偏差，并持续到未纠正的运动偏移。这些结果表明，固定化影响方向规划和早期运动控制过程。我们认为，本体感觉剥夺损害了肢体位置的感知，导致运动指令选择更慢和更不准确。总的来说，我们认为缺乏本体感觉反馈和影响拷贝可能会影响24 h固定后运动规划的准确性，这可能反映了与内部模型机制相关的过程的变化。

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引用次数: 0

TEMPOL alleviated tau pathology and cognitive deficits induced by P301S-tau TEMPOL减轻了P301S-tau诱导的tau病理和认知缺陷。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-22 DOI: 10.1016/j.neulet.2025.138465

Xiao Li , Ruijuan Liu , Ye He , Xifei Yang , Ting Li , Yan Feng

Alzheimer’s disease (AD) is the most frequent of neurodegenerative disease affecting elderly people. However, there is still no curative therapeutic strategies in clinical practice. Here, we studied whether TEMPOL as a free radical scavenger can prevent memory deficits in P301S-tau mice. We found that TEMPOL administration markedly restored learning and memory impairments inducing by P301S-tau. We showed that TEMPOL had a potent capacity of inhibiting the expression of tau protein and its phosphorylation levels. The inflammatory response and synaptic defects induced by P301S-tau was also obviously improved TEMPOL treatment. Furthermore, proteomics showed 121 reversed proteins by TEMPOL treatment were primarily involved in immune system processes, innate immune responses, inflammatory responses, autophagosome assembly, lysosome organization, and autophagy. Taken together, TEMPOL played a critical role in P301S-tau-related cognitive impairments. These findings demonstrate that TEMPOL shows promise as a multi-target therapeutic agent for AD by modulating critical pathways implicated in its pathogenesis.

阿尔茨海默病（AD）是影响老年人的最常见的神经退行性疾病。然而，在临床实践中仍没有有效的治疗策略。在这里，我们研究了TEMPOL作为自由基清除剂是否可以预防P301S-tau小鼠的记忆缺陷。我们发现TEMPOL可以明显恢复P301S-tau诱导的学习和记忆障碍。我们发现TEMPOL具有抑制tau蛋白表达及其磷酸化水平的有效能力。经TEMPOL处理后，P301S-tau诱导的炎症反应和突触缺陷也明显改善。此外，蛋白质组学显示，经TEMPOL处理的121个逆转蛋白主要参与免疫系统过程、先天免疫反应、炎症反应、自噬体组装、溶酶体组织和自噬。综上所述，TEMPOL在p301s tau相关的认知障碍中发挥了关键作用。这些发现表明TEMPOL通过调节与AD发病机制相关的关键途径，有望成为AD的多靶点治疗剂。

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引用次数: 0

Transcutaneous auricular vagus nerve stimulation promotes post-spinal cord injury remyelination via α7nAChR-mediated activation of oligodendrocyte precursor cells 经皮耳迷走神经刺激通过α 7nachr介导的少突胶质前体细胞活化促进脊髓损伤后再髓鞘形成。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-26 DOI: 10.1016/j.neulet.2025.138466

Lingxia Min , Cheng Cheng , Jiafei Chen , Chao Ma , Jilan Wang , Mingliang Tan , Ran Ran , Xiaoyu Wu , Rubing Yan , Jingming Hou , Hongliang Liu , Zhou Feng

Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique with emerging therapeutic potential for various central nervous system diseases. However, its therapeutic effects and mechanisms in spinal cord injury (SCI) remain largely unexplored. In this study, we demonstrated that ta-VNS significantly improved motor function recovery in SCI patients. Diffusion tensor imaging (DTI) further indicated that ta-VNS promoted structural repair of injured axons and myelin sheaths. Using a rodent model of SCI, we found that ta-VNS facilitated remyelination, attenuated tissue damage, and enhanced motor function recovery. Mechanistically, ta-VNS upregulated the expression of the α7 nicotinic acetylcholine receptor (α7nAChR) in oligodendrocyte precursor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes, thereby supporting remyelination. These beneficial effects of ta-VNS were abolished by administration of a selective α7nAChR antagonist. This study identifies the α7nAChR-mediated pro-myelination axis as a novel mechanistic basis for ta-VNS therapy, thereby establishing this non-invasive neuromodulation as a compelling strategy for promoting repair and recovery after SCI.

经皮耳迷走神经刺激（ta-VNS）是一种无创神经调节技术，在多种中枢神经系统疾病的治疗中具有新兴的潜力。然而，其在脊髓损伤（SCI）中的治疗作用和机制在很大程度上仍未被探索。在这项研究中，我们证明了ta-VNS可以显著改善SCI患者的运动功能恢复。弥散张量成像（DTI）进一步显示ta-VNS促进了损伤轴突和髓鞘的结构修复。通过啮齿类动物脊髓损伤模型，我们发现ta-VNS促进髓鞘再生，减轻组织损伤，增强运动功能恢复。在机制上，ta-VNS上调α7烟碱乙酰胆碱受体（α7nAChR）在少突胶质前体细胞（OPCs）中的表达，促进其向成熟少突胶质细胞的增殖和分化，从而支持髓鞘再生。ta-VNS的这些有益作用被选择性α7nAChR拮抗剂所消除。本研究确定α 7nachr介导的前髓鞘轴是ta-VNS治疗的新机制基础，从而确立了这种非侵入性神经调节作为促进脊髓损伤后修复和恢复的有力策略。

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引用次数: 0

Involvement of the right inferior parietal lobule network in ipsilateral spatial attention 同侧空间注意中右侧顶叶下小叶网络的受累。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-20 DOI: 10.1016/j.neulet.2025.138463

Marino Iwakiri , Yuhi Takeo , Takashi Ikeda , Masayuki Hara , Hisato Sugata

Unilateral spatial neglect (USN) significantly impairs mobility in patients following a stroke. The amount and quality of evidence supporting effective treatments for USN is still limited, primarily due to the unclear nature of its underlying neural mechanisms. As lesions in USN are not localized to a specific brain region, research has underscored the importance of evaluating USN from a network-based perspective. Nevertheless, the key functional regions at the core of this network are yet to be identified. Previously, we reported that the right inferior parietal lobule (IPL) may serve as the central hub in the neural network associated with USN. Therefore, this study aimed to determine the brain network centered on the right IPL by conducting seed-based functional connectivity analysis. Our results may contribute to a better understanding of the neural mechanisms in USN.

单侧空间忽视（USN）显著损害中风后患者的活动能力。支持USN有效治疗的证据的数量和质量仍然有限，主要是由于其潜在神经机制的不明确性质。由于USN的病变不局限于特定的大脑区域，研究强调了从基于网络的角度评估USN的重要性。然而，该网络核心的关键功能区域尚未确定。在此之前，我们报道了右侧顶叶下小叶（IPL）可能是与USN相关的神经网络的中心枢纽。因此，本研究旨在通过基于种子的功能连通性分析，确定以右侧IPL为中心的大脑网络。我们的结果可能有助于更好地理解USN的神经机制。

引用次数: 0

Everolimus ameliorates cognitive deficits and synaptic dysfunction in mice with prefrontal cortical ADNP knockdown 依维莫司可改善前额皮质ADNP缺失小鼠的认知缺陷和突触功能障碍。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-19 DOI: 10.1016/j.neulet.2025.138460

Yu Xiang , Zeyu Zhang , Yunrui Jiang , Hongen Wei

Activity-dependent neuroprotective protein (ADNP), a major risk gene for autism spectrum disorder (ASD) and intellectual disability (ID), is critical for brain development and cognition. Among its regulated processes, autophagy is notably affected, with mTORC1 overactivation acting as a negative regulator and frequently reported in ASD. Rapamycin can rescue ASD-related behaviors, and everolimus (EVR), an optimized derivative, is widely applied in clinical practice. However, its role in ADNP-related pathology remains unknown. Here, we established a prefrontal cortex (PFC) ADNP knockdown (KD) mouse model to examine behavioral and molecular consequences, and whether EVR provides benefit. We found that ADNP KD resulted in mTORC1 pathway activation, autophagy impairment, learning and memory deficits, and anxiety-like behaviors, concurrent with dysregulation of microtubule and synaptic proteins. Daily intraperitoneal EVR (5 mg/kg) can effectively alleviate the behavioral and molecular phenotypes caused by ADNP deficiency in the PFC, thereby establishing a strong rationale for targeting the mTOR pathway in treating ADNP-related cognitive impairments.

活动依赖性神经保护蛋白（ADNP）是自闭症谱系障碍（ASD）和智力残疾（ID）的主要风险基因，对大脑发育和认知至关重要。在其受调节的过程中，自噬受到显著影响，mTORC1过度激活作为负调节因子，在ASD中经常被报道。雷帕霉素可以挽救asd相关行为，其优化衍生物依维莫司（everolimus， EVR）被广泛应用于临床。然而，其在adnp相关病理中的作用尚不清楚。在这里，我们建立了一个前额皮质（PFC） ADNP敲低（KD）小鼠模型，以研究行为和分子后果，以及EVR是否提供益处。我们发现ADNP KD导致mTORC1通路激活、自噬损伤、学习和记忆缺陷以及焦虑样行为，同时伴有微管和突触蛋白的失调。每日腹腔内EVR（5 mg/kg）可有效缓解PFC中ADNP缺乏引起的行为和分子表型，从而为靶向mTOR途径治疗ADNP相关认知障碍建立了强有力的理论基础。

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引用次数: 0

Piracetam reverses scopolamine-induced memory disorder in mice: an animal model using behavioral, oxidative, and cholinesterase biomarkers 吡拉西坦逆转小鼠东莨菪碱诱导的记忆障碍：使用行为，氧化和胆碱酯酶生物标志物的动物模型。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-10 Epub Date: 2025-11-19 DOI: 10.1016/j.neulet.2025.138462

Valfran da Silva Lima , Guilherme Luz Emerick , Valéria Dornelles Gindri Sinhorin , Ritane Rose da Silva Lima , Helidi Schaiane da Silva , Kaiany Fernanda da Silva , Antônio Carlos Alves de Sousa , Francielly Rieger Silveira , Amanda Lika Mizuno Saito , Evelyn Lezzo Estevam , Márcia Queiroz Latorraca

Memory impairment diseases have become a serious health problem worldwide. In this context, an animal model capable of recognizing substances with the ability to recover memory disorders would be welcome. Thus, the present work aims to evaluate the effect of piracetam on reversal of scopolamine-induced memory deficit in male Swiss mice (n = 6) after fifteen days of treatment. To achieve this objective, behavioral, oxidative and cholinesterase inhibition markers were used. Memory impairment was evaluated by object and social recognition and step-down inhibitory avoidance tests. The evaluation of the redox state included superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, thiobarbituric acid reactive substances, carbonyl proteins, ascorbic acid, and reduced glutathione. Scopolamine caused cognitive deficit, evidenced by the reduction in latency period and in the discrimination index (DI) of aversive, social, and declarative memories. However, piracetam significantly reversed those deficits. Scopolamine has increased the levels of thiobarbituric acid reactive substances. Scopolamine inhibited significantly brain and plasma cholinesterase activity. In conclusion, scopolamine at a dose of 0.8 mg/kg for 15 days induced memory deficit, oxidative damage and cholinesterase inhibition in brain of mice. Furthermore, piracetam at a dose of 200 mg/kg could reverse the memory impairment induced by scopolamine by mechanisms that are independent of the antioxidant action and cholinesterase inhibition. The present model has showed great sensibility and could be used to evaluate other drugs with the potential for the treatment of diseases related to memory damage.

记忆障碍疾病已成为世界范围内严重的健康问题。在这种情况下，一种能够识别具有恢复记忆障碍能力的物质的动物模型将受到欢迎。因此，本研究旨在评估吡拉西坦在治疗15天后对雄性瑞士小鼠（n = 6）东莨菪碱诱导的记忆缺陷的逆转作用。为了达到这个目的，使用了行为、氧化和胆碱酯酶抑制标记。通过对象识别和社会识别以及降压抑制回避测试评估记忆障碍。氧化还原状态的评价包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽s-转移酶、谷胱甘肽过氧化物酶、硫代巴比妥酸活性物质、羰基蛋白、抗坏血酸和还原性谷胱甘肽。东莨菪碱可导致认知缺陷，其表现为潜伏期的缩短以及厌恶记忆、社交记忆和陈述性记忆的辨别指数（DI）的降低。然而，吡拉西坦显著扭转了这些缺陷。东莨菪碱增加了硫代巴比妥酸反应物质的水平。东莨菪碱显著抑制脑和血浆胆碱酯酶活性。结果表明，0.8 mg/kg东莨菪碱给药15 d可引起小鼠大脑记忆缺损、氧化损伤和胆碱酯酶抑制。此外，200 mg/kg剂量的吡拉西坦可以通过不依赖于抗氧化作用和胆碱酯酶抑制的机制逆转东莨菪碱引起的记忆障碍。目前的模型显示出很强的敏感性，可以用来评估其他有可能治疗与记忆损伤相关疾病的药物。

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引用次数: 0

Constraint-induced movement therapy combined with Nogo-A downregulation enhances corticospinal tract remodeling and motor function in hemiplegic cerebral palsy mice 约束运动疗法联合Nogo-A下调可增强偏瘫脑瘫小鼠皮质脊髓束重构和运动功能。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-01 Epub Date: 2025-11-15 DOI: 10.1016/j.neulet.2025.138447

Yuan Huang , Yunlan Xie , Liru Liu , Danxia Fan , Wen Le , Xiaoying Zhang , Tingting Peng , Wenhui Li , Huijuan Lin , Lu He , Hongmei Tang , Kaishou Xu

Constraint-induced movement therapy (CIMT) enhances hand function in hemiplegic cerebral palsy (HCP) and stroke, partly by strengthening corticospinal tract (CST) projections, while down-regulated Nogo-A has been shown to facilitate neural regeneration in stroke and multiple sclerosis. However, their combined therapeutic effect remains unclear. Therefore, this study explored the impact of CIMT combined with Nogo-A downregulation on CST remodeling and motor function in HCP mice. Mice were randomly assigned to five groups: control, HCP, HCP + CIMT, HCP + SN (siRNA-Nogo-A treatment) and HCP + SN + CIMT. Rotarod and grip test were performed to assess the motor function. Western blot and immunofluorescence staining were performed to quantify Nogo-A and PKCγ expression in the M1 region. Diffusion tensor imaging and transmission electron microscopy were applied to assess fractional anisotropy (FA) of CST and myelin remodeling. Compared with controls, the HCP group exhibited significant motor dysfunction and myelin impairment, characterized by increased Nogo-A expression, decreased PKCγ expression, and reduced FA value of CST (p < 0.05). In contrast, mice treated with CIMT or SN exhibited improved motor function, reduced Nogo-A expression, elevated PKCγ expression, increased FA value of CST, and enhanced myelin remodeling compared with the HCP group (p < 0.05). Notably, CIMT and SN exerted synergistic effects, as the HCP + SN + CIMT group outperformed either single-treatment group (p < 0.05). These findings suggest CIMT combined with Nogo-A downregulation synergistically enhances motor function in HCP mice by reducing Nogo-A expression in M1 region and promoting CST remodeling.

约束诱导运动疗法（CIMT）增强偏瘫脑瘫（HCP）和中风患者的手部功能，部分是通过增强皮质脊髓束（CST）投射，而下调Nogo-A已被证明可促进中风和多发性硬化症患者的神经再生。然而，它们的联合治疗效果尚不清楚。因此，本研究探讨了CIMT联合Nogo-A下调对HCP小鼠CST重塑和运动功能的影响。小鼠随机分为5组：对照组、HCP、HCP + CIMT、HCP + SN （siRNA-Nogo-A治疗）和HCP + SN + CIMT。采用旋转杆和握力试验评估运动功能。Western blot和免疫荧光染色定量检测M1区Nogo-A和PKCγ的表达。应用扩散张量成像和透射电镜观察CST各向异性分数（FA）和髓鞘重塑。与对照组相比，HCP组表现出明显的运动功能障碍和髓磷脂损伤，其特征是Nogo-A表达增加，pkc - γ表达降低，CST FA值降低(p

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引用次数: 0

Neuro-protection of swertisin against impairment induced by Aβ25-35 by acting on COX-2 to up-regulate 2-AG and suppressing neuroinflammation 獐牙菜素通过作用于COX-2上调2-AG和抑制神经炎症对Aβ25-35损伤的神经保护作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2026-01-01 Epub Date: 2025-10-28 DOI: 10.1016/j.neulet.2025.138429

Jiang Wu , Lijin Zhou , Chao Lang

Ziziphi Spinosae Semen (Suan Zao Ren) is a traditional Chinese medicine with the functions of nourishing the heart and liver, calming the mind, and stopping sweating. Swertisin, one of the main active ingredients in Ziziphi Spinosae Semen, has a wide range of pharmacological effects such as anti-inflammation, anti-oxidation, and enhancement of learning and memory. Based on the Aβ cascade and the neuroinflammatory theory, combined with the anti-inflammatory neuroprotective effect of endocannabinoid 2-AG, this work integrated modern biochemical technology methods such as liquid chromatography-mass spectrometry, Western blot, and electrophysiological technique to explore the neuroprotective effects and potential mechanism of swertisin on the Alzheimer’s disease (AD) model induced by Aβ_25-35. The results showed that swertisin relieved impairment of learning and memory caused by Aβ_25-35 on hippocampus slice by decreasing COX-2 expression and inhibiting COX-2 activity to up-regulate the endogenous 2-AG, and suppressing neuroinflammation and neuronal apoptosis via CB1R-dependent NF-κB pathway. It was further discovered that swertisin protected the primary hippocampal neurons, reduced over-expression of COX-2, and relieved the neuroinflammatory against Aβ_25-35 through the CB1R-dependent NF-κB signaling pathway. Finally, it was confirmed that swertisin alleviated BV-2 cell apoptosis induced by Aβ_25-35. These results help us understand the mechanism of swertisin against AD and promote the development of related drugs and healthy products.

酸枣仁（酸枣仁）是一种传统的中药，具有滋补心肝、安神、止汗的作用。獐牙菜素是酸枣中的主要活性成分之一，具有抗炎、抗氧化、增强学习记忆等广泛的药理作用。本研究基于Aβ级联反应和神经炎症理论，结合内源性大麻素2-AG的抗炎神经保护作用，结合液相色谱-质谱、Western blot、电生理技术等现代生化技术手段，探讨獐角菜素对Aβ25-35诱导的阿尔茨海默病（AD）模型的神经保护作用及其潜在机制。结果表明，獐尾鱼素可通过降低COX-2表达和抑制COX-2活性上调内源性2-AG，通过cb1r依赖的NF-κB通路抑制神经炎症和神经元凋亡，缓解a - β25-35在海马片上引起的学习记忆障碍。进一步发现獐牙菜素通过cb1r依赖的NF-κB信号通路，保护海马原代神经元，降低COX-2的过表达，减轻a - β25-35的神经炎症。最后证实獐牙菜素可减轻a - β25-35诱导的BV-2细胞凋亡。这些结果有助于我们了解獐牙菜素抗AD的作用机制，促进相关药物和保健品的开发。

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引用次数: 0