Neuroscience Letters最新文献_第3页

MEGF10 knockout promotes cortical and hippocampal amyloid deposition in AD mouse model 在AD小鼠模型中，敲除MEGF10促进皮层和海马淀粉样蛋白沉积。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-06 DOI: 10.1016/j.neulet.2025.138487

Yu Fujita , Taichi Yabe , Yoshikazu Yamada , Ryo Kiuchi , Motoi Nagase , Ryosuke Nakamori , Seisuke Ichikawa , Takahide Obara , Hibiki Yasuda , Jyoichiro Kurano , Tsubasa Honda , Hiroto Komano , Kun Zou , Yoshiyuki Tanabe , Tomoji Maeda

Multiple epidermal growth factor (EGF)-like domains 10 (MEGF10) is a single-pass transmembrane protein expressed in neurons and astrocytes, functioning as a phagocytic receptor for apoptotic cells and mediating homotypic adhesion in the mammalian brain. We previously demonstrated that MEGF10 facilitates the uptake of toxic amyloid-β (Aβ) species Aβ42 and Aβ43 by neurons and astrocytes in vitro. However, whether MEGF10 also serves as a phagocytic receptor for Aβ in the brain in vivo, particularly under neurodegenerative conditions such as Alzheimer’s disease (AD), remains unclear. To address this question, we generated MEGF10 knockout mice on an AD model background and analyzed brain Aβ deposition and Aβ42 levels. We observed a significant increase in Aβ deposition and Aβ42 levels in the hippocampus and cortex of MEGF10-deficient AD mice compared with AD model controls. To assess cognitive function, we performed the Y-maze test. MEGF10 knockout AD mice exhibited impaired spatial memory relative to wild-type controls; however, no significant difference was found between MEGF10 knockout AD mice and AD model controls. These findings suggest that MEGF10 contributes to Aβ clearance in the brain and support its role as a phagocytic receptor for Aβ in vivo, potentially helping to maintain brain homeostasis in the context of Alzheimer’s pathology.

多表皮生长因子（EGF）样结构域10 （MEGF10）是一种在神经元和星形胶质细胞中表达的单代跨膜蛋白，在哺乳动物大脑中作为凋亡细胞的吞噬受体并介导同型粘附。我们之前在体外证明了MEGF10促进了神经元和星形胶质细胞对毒性淀粉样蛋白-β (Aβ)物种Aβ42和Aβ43的摄取。然而，MEGF10是否也在体内的大脑中作为a β的吞噬受体，特别是在阿尔茨海默病（AD）等神经退行性疾病中，仍不清楚。为了解决这个问题，我们在AD模型背景下产生了MEGF10敲除小鼠，并分析了脑Aβ沉积和Aβ42水平。我们观察到，与AD模型对照组相比，megf10缺陷AD小鼠海马和皮层中a β沉积和a β42水平显著增加。为了评估认知功能，我们进行了y形迷宫测试。与野生型对照相比，MEGF10基因敲除的AD小鼠表现出空间记忆受损；然而，在MEGF10基因敲除AD小鼠和AD模型对照组之间没有发现显著差异。这些发现表明，MEGF10有助于大脑中a β的清除，并支持其作为体内a β吞噬受体的作用，可能有助于在阿尔茨海默病病理背景下维持大脑稳态。

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引用次数: 0

NNT inhibits microglial activation via mitochondrial oxidative stress in spinal cord injury NNT通过线粒体氧化应激抑制脊髓损伤中的小胶质细胞激活。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-05 DOI: 10.1016/j.neulet.2025.138486

Ming Li , Qiuyue Gu , Zhenyu Fan , Chengwei Duan

Spinal cord injury (SCI) is a major public health challenge, often leading to severe neurological and physical disabilities. Microglia, the primary immune cells in the spinal cord, play critical roles in both the physiology and pathology of SCI. A deeper understanding of microglial activation is thus crucial for developing new therapeutic strategies. In this study, we observed that nicotinamide nucleotide transhydrogenase (NNT), a mitochondrial protein in eukaryotic cells, was upregulated in the injured spinal cord of mice, coinciding with elevated inflammatory factors and microglial activation. In vitro, lipopolysaccharide (LPS) induced microglial activation and increased NNT expression in BV2 cells. NNT overexpression effectively mitigated LPS-induced inflammation, proliferation, and oxidative stress in BV2 microglia. Furthermore, treatment with the mitochondria-targeting peptide SS-31 reduced mitochondrial superoxide levels. SS-31 also suppressed the inflammatory, proliferative, and oxidative stress responses caused by NNT deficiency in BV2 cells. Critically, in vivo overexpression of NNT in the spinal cord attenuated microglial activation and promoted functional recovery after SCI. Our findings reveal that NNT suppresses microglial activation by modulating mitochondrial oxidative stress, offering a promising therapeutic avenue for SCI.

脊髓损伤（SCI）是一个重大的公共卫生挑战，经常导致严重的神经和身体残疾。小胶质细胞是脊髓中的初级免疫细胞，在脊髓损伤的生理和病理中起着至关重要的作用。因此，更深入地了解小胶质细胞的激活对于开发新的治疗策略至关重要。在这项研究中，我们观察到真核细胞中的线粒体蛋白烟酰胺核苷酸转氢酶（NNT）在小鼠损伤脊髓中上调，与炎症因子升高和小胶质细胞激活相一致。在体外，脂多糖（LPS）诱导BV2细胞的小胶质细胞活化并增加NNT的表达。NNT过表达可有效减轻脂多糖诱导的BV2小胶质细胞炎症、增殖和氧化应激。此外，线粒体靶向肽SS-31治疗降低了线粒体超氧化物水平。SS-31还能抑制由NNT缺乏引起的BV2细胞炎症、增殖和氧化应激反应。至关重要的是，脊髓中NNT的体内过度表达减弱了脊髓损伤后小胶质细胞的激活并促进了功能恢复。我们的研究结果表明，NNT通过调节线粒体氧化应激来抑制小胶质细胞的激活，为脊髓损伤提供了一个有希望的治疗途径。

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引用次数: 0

The impact of guanethidine-induced sympathectomy on satellite glial cell activation in a rat model of neuropathic pain 胍乙啶诱导的交感神经切除术对神经性疼痛大鼠模型卫星神经胶质细胞活化的影响。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-02 DOI: 10.1016/j.neulet.2025.138483

Xicun Han , Xiaohua Jiang , Yabin Liu , Guowu Chen

The involvement of satellite glial cells (SGCs) in neuropathic pain has been well-established; however, it remains unclear whether the sprouted sympathetic fibers within the dorsal root ganglion (DRG) after peripheral nerve injury affect the activation of SGCs. A rat model of neuropathic pain induced by spinal nerve ligation injury (SNL) was established. The mechanical withdrawal threshold (MWT) was evaluated using the von Frey test on postoperative days (POD) 1, 3, 7, and 14 to quantify mechanical allodynia. Immunofluorescence staining was performed to detect the expression of glial fibrillary acidic protein (GFAP, a marker for activated SGCs), tyrosine hydroxylase (TH, a marker for sympathetic nerve fibers), and α2-adrenergic receptor (α2-AR) in the ipsilateral DRG. Reversible sympathectomy was achieved by means of a single high-dose intraperitoneal injection of guanethidine (Gua). Western blotting(WB) was used to assess the effect of sympathectomy on GFAP expression in the DRG of SNL rats. After spinal nerve injury, the MWT of the ipsilateral hindlimb in rats decreased rapidly. Immunofluorescence results confirmed that the expression levels of GFAP and TH in the ipsilateral DRG of SNL rats gradually increased along with the development of mechanical allodynia. Notably, the co-expression of α2-AR and GFAP in the DRG gradually increased after SNL, suggesting that the newly formed noradrenergic-SGCs signaling within the DRG was involved in the initiation and maintenance of neuropathic pain. On 14 days post-SNL, Gua-induced sympathectomy significantly alleviated mechanical allodynia in rats and remarkably inhibited GFAP expression in the ipsilateral DRG. We concluded that in the rat model of neuropathic pain induced by SNL, the sprouted sympathetic fibers within the DRG may also participate in the maintenance of neuropathic pain by regulating the activation of SGCs.

卫星神经胶质细胞（SGCs）在神经性疼痛中的作用已得到证实；然而，周围神经损伤后背根神经节（DRG）内出现的交感神经纤维是否影响上神经细胞的激活尚不清楚。建立大鼠脊神经结扎损伤（SNL）致神经性疼痛模型。术后第1、3、7、14天采用von Frey试验评估机械戒断阈值（MWT），量化机械异常性痛。免疫荧光染色检测同侧DRG中胶质纤维酸性蛋白（GFAP）、酪氨酸羟化酶（TH）和α2-肾上腺素能受体（α2-AR）的表达。可逆交感神经切除术是通过单次高剂量的鸟乙啶腹腔注射（Gua）实现的。采用Western blotting（WB）方法观察交感神经切除术对SNL大鼠DRG中GFAP表达的影响。脊髓神经损伤后，大鼠同侧后肢MWT迅速下降。免疫荧光结果证实，GFAP和TH在SNL大鼠同侧DRG中的表达水平随着机械异常性疼痛的发展而逐渐升高。值得注意的是，SNL后DRG中α2-AR和GFAP的共表达逐渐增加，提示DRG内新形成的去甲肾上腺素能- sgcs信号参与了神经性疼痛的发生和维持。在snl后14 天，瓜氨酸诱导的交感神经切除术显著减轻了大鼠的机械异常性痛，并显著抑制了同侧DRG中GFAP的表达。我们认为，在SNL诱导的神经性疼痛大鼠模型中，DRG内萌发的交感神经纤维也可能通过调节SGCs的激活参与神经性疼痛的维持。

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引用次数: 0

Facilitation of supplementary motor area activity modulates the sense of effort: a theta burst stimulation study 辅助运动区活动的促进调节努力感：一项θ波爆发刺激研究。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-01 DOI: 10.1016/j.neulet.2025.138482

Taishi Okegawa , Daiki Yamasaki , Naotsugu Kaneko , Kimitaka Nakazawa

The sense of effort, defined as the phenomenological experience of invested physical resources in the task, is a critical component of motor control. The supplementary motor area (SMA) has been implicated in generating this sense, yet it remains unclear how modulating SMA activity affects unconscious motor output when individuals intend to exert the same level of effort. The present study aimed to investigate how inhibiting and facilitating SMA activity influences the subjective sense of effort and associated motor output.

Twelve healthy volunteers received both facilitatory and inhibitory theta burst transcranial magnetic stimulation (TBS) applied to the SMA. We assessed corticospinal excitability, submaximal effort force production in an index finger abduction task (at a subjective effort level of 35% without visual feedback), and force-matching performance before and after the TBS protocols.

Results showed that facilitatory TBS led to a significant reduction in the submaximal index finger abduction force, which was accompanied by decreased EMG activity. In contrast, inhibitory TBS did not produce significant changes in submaximal force. Importantly, TBS applied to the SMA did not significantly alter motor-evoked potentials, indicating that corticospinal excitability remained unchanged. These findings suggest that enhanced SMA activity increases the effort required to produce a given force. The underlying mechanism likely involves changes in efference copy signals, as the effect occurred without altering the corticospinal excitability. In addition, force-matching performance was improved at 30 min after facilitatory TBS applied to the SMA. This delayed behavioral improvement may suggest a time-dependent modulation of sensorimotor processing, possibly involving the SMA and posterior parietal cortex, although network-level mechanisms remain speculative.

This study provides causal evidence for the SMA’s role in processing effort-related signals and contributes to a growing understanding of the cortical mechanisms underlying the sense of effort.

努力感被定义为在任务中投入体力资源的现象学经验，是运动控制的关键组成部分。辅助运动区（SMA）与产生这种感觉有关，但当个体打算施加相同水平的努力时，调节SMA活动如何影响无意识运动输出仍不清楚。本研究旨在探讨抑制和促进SMA活动如何影响主观努力感和相关的运动输出。12名健康志愿者同时接受了促进性和抑制性经颅磁刺激（TBS）。我们评估了皮质脊髓兴奋性、食指外展任务（在没有视觉反馈的情况下主观努力水平为35%）的次最大努力力产生，以及TBS方案前后的力匹配表现。结果表明，促进性TBS可显著降低大鼠食指次最大外展力，并伴有肌电活动降低。相比之下，抑制性TBS不产生显著的亚极大力变化。重要的是，对SMA施加TBS并没有显著改变运动诱发电位，这表明皮质脊髓兴奋性保持不变。这些发现表明，增强的SMA活动增加了产生给定力所需的努力。潜在的机制可能涉及到影响复制信号的变化，因为这种效应发生时没有改变皮质脊髓的兴奋性。此外，在30 min时，将促进性TBS应用于SMA后，力匹配性能得到改善。这种延迟的行为改善可能表明感觉运动加工的时间依赖性调节，可能涉及SMA和后顶叶皮层，尽管网络层面的机制仍然是推测性的。本研究为SMA在处理努力相关信号中的作用提供了因果证据，并有助于加深对努力感背后的皮层机制的理解。

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引用次数: 0

Structure–function characterization of Olea dioica Roxb. PGK-1: Acetylcholinesterase inhibition, molecular docking, and amelioration of Aβ40-induced toxicity in SH-SY5Y neuronal cells and the UAS-Aβ42; ey-GAL4 drosophila model of Alzheimer’s disease 油橄榄PGK-1的结构-功能表征：乙酰胆碱酯酶抑制、分子对接和改善a - β42对SH-SY5Y神经元细胞和uas - a - β42的毒性眼- gal4果蝇阿尔茨海默病模型

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-26 DOI: 10.1016/j.neulet.2025.138467

G.K. Pratap , Pramod G Nagaraju , Chandrashekhar G. Joshi , Lokesh Koodlur Sannegowda , Manjula Shantaram , Poornima Priyadarshini

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 : 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 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 : 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

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 : 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

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 : 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

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 : 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