Neuroscience Letters最新文献_第4页

Chlorogenic acid exerts anti-inflammation and neuroprotective effect in pentylenetetrazole-induced epilepsy mouse model by regulating microglia polarization via Nrf2/HO-1 pathway 绿原酸通过Nrf2/HO-1通路调节小胶质细胞极化，在戊四唑致癫痫小鼠模型中发挥抗炎和神经保护作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-19 DOI: 10.1016/j.neulet.2025.138493

Yi Sun , Jiayu Wang , Aoyuan Zhang , Ankang Hu , Lianlian Wu

Chlorogenic acid (CGA) possesses diverse biological functions, including antioxidant, anti-inflammatory, and anti-apoptotic, both in vitro and in vivo. Recent studies have suggested that CGA also has neuroprotective effects. However, its potential to alleviate seizures and attenuate epilepsy-related neuropathology remains unclear. This study investigated the effects and underlying mechanisms of CGA in a pentylenetetrazole (PTZ)-induced epilepsy mouse model. CGA treatment significantly reduced epileptic seizures. Nissl and NeuN immunofluorescence staining revealed that CGA also significantly reduced neuronal damage. Furthermore, CGA promoted microglial polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype and suppressed neuroinflammation, evidenced by iNOS/IBA-1 and Arg-1/IBA-1 immunofluorescence and RT-PCR. BrdU staining revealed that CGA inhibited epilepsy-induced aberrant neurogenesis. In addition, behavioral tests showed improved cognitive performance following CGA treatment. Finally, western blot analysis indicated the activation of the Nrf2/HO-1 pathway, and Nrf2 knockdown reversed CGA’s effects. These findings suggest that CGA exerts anti-seizure and neuroprotective effects via microglial modulation through the Nrf2/HO-1 pathway.

绿原酸（Chlorogenic acid， CGA）在体内体外均具有抗氧化、抗炎、抗细胞凋亡等多种生物学功能。最近的研究表明，CGA也有神经保护作用。然而，其减轻癫痫发作和减轻癫痫相关神经病理的潜力仍不清楚。本研究探讨了CGA在戊四唑（PTZ）诱导癫痫小鼠模型中的作用及其机制。CGA治疗显著减少癫痫发作。Nissl和NeuN免疫荧光染色显示，CGA还能显著减轻神经元损伤。此外，通过iNOS/IBA-1和Arg-1/IBA-1免疫荧光和RT-PCR， CGA促进小胶质细胞从促炎M1表型向抗炎M2表型极化，抑制神经炎症。BrdU染色显示CGA抑制癫痫诱导的异常神经发生。此外，行为测试显示CGA治疗后认知能力有所改善。最后，western blot分析表明Nrf2/HO-1通路激活，Nrf2敲低逆转了CGA的作用。这些发现表明，CGA通过Nrf2/HO-1途径调节小胶质细胞发挥抗癫痫和神经保护作用。

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引用次数: 0

Antinociceptive role of IL-10/STAT3 signaling in trigeminal neuropathic pain male rat model through Pomc and β-endorphin IL-10/STAT3信号通过Pomc和β-内啡肽在三叉神经性疼痛雄性大鼠模型中的抗伤害感受作用

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-18 DOI: 10.1016/j.neulet.2025.138492

Lutfi Putra Perdana , Jaime Fabillar Jr , Dara Sari Arini , Swarnalakshmi Raman , Resmi Raju , Daisuke Ikutame , Masamitsu Oshima , Keiko Miyoshi , Yoshizo Matsuka

Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of recombinant IL-10 (rIL-10) in a rat model of infraorbital nerve constriction. Using male Sprague-Dawley rats, we administered rIL-10 or phosphate-buffered saline to the intra-trigeminal ganglion and observed a peak analgesic effect at 4 h post-injection in the rIL-10 group. Real-time PCR demonstrated significant upregulation of the Proopiomelanocortin (Pomc) gene in rIL-10-treated rats, with immunofluorescence staining confirming increased expression of bioactive peptide β-endorphin (β-END) in the same group. In situ hybridization assay further localized Pomc expression to satellite glial cells and neurons in the trigeminal ganglion, with β-END exhibiting a similar distribution. To elucidate the signaling mechanism, we co-administered a STAT3 inhibitor, Stattic, which abolished the analgesic effect of rIL-10, suppressed Pomc upregulation, and reduced β-END expression. These findings indicate that the STAT3 pathway is a critical mediator of rIL-10-induced analgesia, with Pomc and β-END as potential molecular effectors.

白介素-10 （IL-10）是一种对三叉神经性疼痛（TNP）具有镇痛作用的细胞因子。然而，其确切机制尚不清楚。在这项研究中，我们研究了重组IL-10 （IL-10）在眶下神经收缩大鼠模型中的抗感觉作用。我们以雄性Sprague-Dawley大鼠为实验动物，在三叉神经节内注射rIL-10或磷酸盐缓冲盐水，观察il -10组在注射后4 h达到镇痛效果峰值。Real-time PCR结果显示，il -10处理大鼠的Proopiomelanocortin （Pomc）基因显著上调，免疫荧光染色证实同一组大鼠的生物活性肽β-内啡肽（β-END）表达增加。原位杂交实验进一步将Pomc的表达定位到三叉神经节的卫星胶质细胞和神经元中，β-END的表达也表现出类似的分布。为了阐明信号传导机制，我们联合使用STAT3抑制剂Stattic，该抑制剂可消除rIL-10的镇痛作用，抑制Pomc上调，并降低β-END表达。这些发现表明STAT3通路是ril -10诱导的镇痛的关键介质，Pomc和β-END是潜在的分子效应物。

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引用次数: 0

Suppression of 5-HT2 receptor signaling impairs normal eye development in zebrafish 抑制5-HT2受体信号会损害斑马鱼正常的眼睛发育。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-16 DOI: 10.1016/j.neulet.2025.138491

Zulvikar Syambani Ulhaq , Mitsuyo Kishida

Serotonin (5-HT) signaling plays essential roles in vertebrate development beyond neurotransmission, including in ocular morphogenesis. Here, we investigated the effects of Ritanserin, a non-selective 5-HT₂ receptor antagonist, on zebrafish embryonic development with a focus on eye formation. While Ritanserin exposure (0.1–10 μM) did not affect mortality or hatching rates up to 96 h post-fertilization (hpf), higher concentrations (5–10 μM) induced developmental abnormalities, such as microphthalmia, pericardial edema, blood congestion, and craniofacial malformations by 5 days post-fertilization (dpf). Ritanserin significantly reduced the expression of cyp19a1b, encoding brain aromatase (AroB) involved in local estrogen synthesis within the eye, and pax6a, a key regulator of retinal neurogenesis, without altering cyp19a1a levels. Co-treatment with exogenous 5-HT or estradiol (E₂) partially rescued eye size, optic nerve morphology, pax6a expression, and reduced retinal apoptosis. Moreover, visual deficits induced by Ritanserin, as shown by impaired visual background adaptation (VBA) and optomotor responses (OMR), were similarly reversed by 5-HT or E₂. These findings demonstrate that 5-HT₂ signaling is critical for proper eye development in zebrafish, likely through regulation of estrogen synthesis and neuroretinal gene expression, and suggest that serotonergic disruption during early development can lead to structural and functional visual deficits.

5-羟色胺（5-HT）信号在脊椎动物的发育中起着重要的作用，包括神经传递，包括眼形态发生。在这里，我们研究了利坦色林（一种非选择性5-HT2受体拮抗剂）对斑马鱼胚胎发育的影响，重点是眼睛的形成。在受精后96 h （hpf）内，利坦色林暴露（0.1 ~ 10  μM）对死亡率和孵化率没有影响，但在受精后5 d （dpf）内，利坦色林暴露（5 ~ 10  μM）会引起发育异常，如小眼症、心包水肿、充血和颅面畸形。利坦色林显著降低cyp19a1b的表达，cyp19a1b编码脑芳香化酶（AroB），参与眼内局部雌激素合成，pax6a是视网膜神经发生的关键调节因子，而cyp19a1a的水平没有改变。外源性5-羟色胺或雌二醇（E2）联合治疗部分恢复了眼睛大小、视神经形态、pax6a表达，并减少了视网膜凋亡。此外，利坦色林引起的视觉缺陷，如视觉背景适应（VBA）和光运动反应（OMR）受损，同样可以被5-HT或E2逆转。这些发现表明，5-HT2信号对斑马鱼正常的眼睛发育至关重要，可能通过调节雌激素合成和神经视网膜基因表达，并表明在早期发育过程中5-羟色胺能中断可能导致结构性和功能性视觉缺陷。

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引用次数: 0

The effects of lithium chloride in N-methyl-N-nitrosourea induced retinal damage in rats 氯化锂对n -甲基-n -亚硝基脲致大鼠视网膜损伤的影响。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-11 DOI: 10.1016/j.neulet.2025.138489

Canan Akdeniz İncili , Yesari Eröksüz , Hatice Eröksüz , Abdullah Aslan

The aim of the current study was to assess the potential neuroprotective effects of lithium chloride (LiCl) against retinal degeneration (RD) induced by N-methyl-N-nitrosourea (MNU) in the rats. 108 rats were assigned to 6 groups: Control, MNU (80 mg/kg), MNU + 30 mg/kg LiCI, MNU + 60 mg/kg LiCI, 30 mg/kg LiCI, and 60 mg/kg LiCI. The experimental groups comprised 18 rats each and the animals were euthanised on the 2nd, 7th and 14th days following the administration of MNU. Compared with the MNU group, both doses of LiCl significantly reduced retinal cell apoptosis and increased retinal thickness (P < 0.05). MNU group had a higher apoptotic index than the treatment groups, as evidenced by increased immunoreactivities of caspase-3, caspase-6, Bax, and 8-OHdG and decreased immunoreactivities of Bcl-2 at day 2. The outer nuclear layer (ONL) of the retina in rats treated with MNU exhibited a significant reduction in comparison the control group on both days 7 and 14 (P < 0.05). In contrast to the MNU-treated figgroup, the LiCl-injected rats exhibited a notable elevation in the expression levels of BDNF and Bcl-2 (P < 0.05). Conversely, the MNU-treated group exhibited markedly increased expression of GSK-3β, Bax, 8-OHdG, caspase-3, and caspase 6 (P < 0.05). In conclusion, LiCl demonstrated dose-dependent neuroprotective effects against MNU-induced RD in rats. These effects included a reduction in retinal cell apoptosis, an improvement in retinal thickness, and the potential involvement of anti-apoptotic mechanisms, glial activation inhibition, and neurotrophic factor modulation.

本研究旨在评估氯化锂（LiCl）对n -甲基-n -亚硝基脲（MNU）所致大鼠视网膜变性（RD）的潜在神经保护作用。将108只大鼠分为6组：对照组、MNU（80 mg/kg）、MNU + 30 mg/kg LiCI、MNU + 60 mg/kg LiCI、30 mg/kg LiCI和60 mg/kg LiCI。各组大鼠18只，分别于给药后第2、7、14天实施安乐死。与MNU组比较，两种剂量的LiCl均显著降低视网膜细胞凋亡，增加视网膜厚度（P < 0.05）。MNU组细胞凋亡指数高于治疗组，表现为第2天caspase-3、caspase-6、Bax和8-OHdG的免疫反应活性升高，Bcl-2的免疫反应活性降低。与对照组相比，MNU处理大鼠视网膜外核层（ONL）在第7天和第14天均显著降低（P < 0.05）。与mnu处理的fig组相比，licl注射大鼠BDNF和Bcl-2表达水平显著升高（P < 0.05）。相反，mnu处理组GSK-3β、Bax、8-OHdG、caspase-3和caspase 6的表达显著增加（P < 0.05）。综上所述，LiCl对mnu诱导的RD具有剂量依赖性的神经保护作用。这些作用包括视网膜细胞凋亡的减少，视网膜厚度的改善，以及抗凋亡机制，神经胶质活化抑制和神经营养因子调节的潜在参与。

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引用次数: 0

Bovine lactoferrin-induced antinociception through 5-HT1A/1D receptors in formalin-induced tonic pain 牛乳铁蛋白通过5-HT1A/1D受体在福尔马林诱导的强直性疼痛中诱导抗炎反应

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 DOI: 10.1016/j.neulet.2025.138490

Sergio Ernesto Ávila-Morales, Maria Elisa Drago-Serrano, Beatriz Godínez-Chaparro

Bovine lactoferrin (bLF) is a multifunctional glycoprotein that displays modulatory effects on pain through pathways not fully known. Therefore, we determined the role of the serotonergic system as a potential mechanism underlying the antinociceptive effect of bLF on formalin-induced tonic nociception. The formalin test was used to assess the antinociceptive effect—pain-like behaviour (flinching) at 1 h. The bLF-induced antinociceptive effect was prevented by the intrathecal (3 µg/rat), but not the intraplantar (30 µg/rat) administration of methiothepin, a non-selective 5-hydroxytryptamine (5-HT) antagonist. Moreover, intrathecal administration of WAY-100635 (6 µg/rat; selective 5-HT_1A receptor antagonist) and BRL1555724 (4 µg/rat; selective 5-HT_1D receptor antagonist) prevented the bLF-induced antinociceptive effect. However, intrathecal administration of SB-224289 (5 µg/rat; selective 5-TH_1B receptor antagonist) and SB-699551 µg/rat; selective 5-TH_5A receptor antagonist) did not prevent the bLF-induced antinociceptive effect. The above finding suggests that bLF reduces acute nociception induced by formalin, and this antinociceptive effect is mediated, at least in part, by the serotonergic system, acting only at the spinal level and not at the peripheral level, via activation of central 5-HT_1A/1D serotonergic receptors.

牛乳铁蛋白（bLF）是一种多功能糖蛋白，通过尚不完全清楚的途径对疼痛表现出调节作用。因此，我们确定了血清素能系统的作用，作为bLF对福尔马林诱导的强直性伤害性的抗伤害性作用的潜在机制。福尔马林试验用于评估1 h时的抗痛觉效应-疼痛样行为（退缩）。鞘内注射（3µg/大鼠）可阻止blf诱导的抗痛觉效应，但足底注射（30µg/大鼠）甲氧thepin（一种非选择性5-羟色胺（5-HT）拮抗剂）不能阻止。此外，鞘内给药WAY-100635（6µg/大鼠，选择性5-HT1A受体拮抗剂）和BRL1555724（4µg/大鼠，选择性5-HT1D受体拮抗剂）可阻止blf诱导的抗伤害感受作用。然而，鞘内给药SB-224289（5µg/大鼠；选择性5- th1b受体拮抗剂）和SB-699551µg/大鼠；选择性5-TH5A受体拮抗剂)不能阻止blf诱导的抗伤害性作用。上述发现表明，bLF可减少福尔马林引起的急性伤害感受，而这种抗伤害感受作用至少部分是由血清素能系统介导的，该系统通过激活中枢5-HT1A/1D血清素能受体，仅在脊髓水平而不在外周水平起作用。

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引用次数: 0

The anti-epileptic mechanism of a ketogenic diet regulating the gut microbiota via SIRT2 activation of the PI3K/AKT signaling pathway 生酮饮食通过SIRT2激活PI3K/AKT信号通路调节肠道微生物群的抗癫痫机制

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-09 DOI: 10.1016/j.neulet.2025.138488

Minghua Li, Haifeng Deng, Ling Ma, Manli Sun

Purpose

Epilepsy (EP) is a disorder caused by sudden abnormal discharges of neurons in the brain. A ketogenic diet (KD) has significant anticonvulsant effects in some epileptic patients, but the signaling pathway remains unclear. This study aims to investigate the mechanisms underlying the anticonvulsant effects of a KD.

Methods

Acute epilepsy models were induced by kainic acid (KA) and pentylenetetrazol (PTZ), synaptic electrical activity in the hippocampus was measured. The effects of KD on the expression levels of postsynaptic proteins and SIRT2 was determined, as well as the phosphorylation of the PI3K and Akt-S-473 signaling pathways. Metabolomic analysis was used to investigate the effect of KD on the gut microbiota.

Results

The KD inhibited acute seizures and promoted the amplitude of induced inhibitory postsynaptic current (IPSC) transmission and the frequency of spontaneous IPSC transmission in cortical brain regions. KD upregulated the expression of PI3K, activated the phosphorylation of AKT-S-473, and increased SIRT2 expression. Metabolomic analysis indicated shifts in host metabolism, particularly involving Clostridiales(e.g., Blautia and Lachnospiraceae). Based on existing literature, we hypothesize tha KD may support gut barrier function and anti-inflammatory responses.

Conclusion

The anti-epileptic effect of KD in the prefrontal cortex is associated with the activation of the PI3K/Akt signaling pathway and an increase in SIRT2 expression. Additionally, our data are consistent with the emerging concept that the anti-seizure effects of KD may also involve modulation of the gut microbiota. This provides valuable insights for the development of new therapeutic interventions.

目的：癫痫（EP）是一种由大脑神经元突然异常放电引起的疾病。生酮饮食（KD）对一些癫痫患者具有显著的抗惊厥作用，但其信号通路尚不清楚。方法：用kainic acid （KA）和pentylenetetrazol （PTZ）诱导急性癫痫模型，测量海马突触电活动。测定KD对突触后蛋白和SIRT2表达水平的影响，以及PI3K和Akt-S-473信号通路的磷酸化。采用代谢组学分析研究KD对肠道菌群的影响。结果：KD能抑制急性发作，提高脑皮质区诱导抑制性突触后电流（IPSC）传递幅度和自发IPSC传递频率。KD上调PI3K的表达，激活AKT-S-473的磷酸化，增加SIRT2的表达。代谢组学分析表明，宿主代谢发生了变化，特别是涉及梭菌(如：，蓝藻和毛螺科)。基于现有文献，我们假设KD可能支持肠道屏障功能和抗炎反应。结论：KD在前额皮质的抗癫痫作用与激活PI3K/Akt信号通路和增加SIRT2表达有关。此外，我们的数据与新兴的概念一致，即KD的抗癫痫作用也可能涉及肠道微生物群的调节。这为开发新的治疗干预措施提供了有价值的见解。

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引用次数: 0

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