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Subanesthetic Ketamine Ameliorates Activity-Based Anorexia of Adult Mice. 亚麻醉氯胺酮改善成年小鼠活动性厌食症。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1002/syn.70005
Yiru Dong, Chiye Aoki

Objective: Anorexia nervosa (AN) is an eating disorder with the second highest mortality of all mental illnesses and high relapse rate, especially among adult females, yet with no accepted pharmacotherapy. A small number of studies have reported that adult females who struggled with severe and relapsing AN experienced sustained remission of the illness following ketamine infusions. Two other reports showed that 30 mg/kg IP ketamine can reduce vulnerability of adolescent mice to activity-based anorexia (ABA), an animal model of AN. However, no study has tested the efficacy of ketamine on adult ABA mice. This study aimed to fill this gap in knowledge.

Methods: Forty-one female mice underwent three cycles of ABA (ABA1, ABA2, and ABA3) to assess relapse vulnerability in adulthood. Of them, 13 received ketamine injections (30 mg/kg, 3 doses) during ABA2 (KET) in adulthood to assess ketamine's acute effects during ABA2 and ketamine's potential for sustained efficacy during ABA3, 10-13 days later. The remaining 28 received vehicle or no injections during ABA2 (CON).

Results: Severe weight loss (>20% of baseline) during ABA3 was observed for 89% of CON but only 69% of KET. Overall wheel running per day was significantly less for KET than CON (p < 0.01) throughout ABA2, including hours of food availability, and these reductions were sustained through ABA3. Food consumption was not altered significantly by ketamine.

Discussion: These findings suggest that ketamine may reduce adult females' vulnerability to ABA and may protect women from AN relapse by reducing hyperactivity.

目的:神经性厌食症(Anorexia神经性厌食症,AN)是所有精神疾病中死亡率和复发率第二高的饮食失调,尤其是在成年女性中,但没有公认的药物治疗方法。少数研究报告说,患有严重和复发性AN的成年女性在注射氯胺酮后病情持续缓解。另外两份报告显示,30 mg/kg IP氯胺酮可以降低青春期小鼠对活动性厌食症(ABA)的易损性,ABA是一种an动物模型。然而,没有研究测试氯胺酮对成年ABA小鼠的功效。本研究旨在填补这一知识空白。方法:41只雌性小鼠接受3个ABA周期(ABA1、ABA2和ABA3),评估成年期复发易感性。其中13例在ABA2 (KET)期间接受氯胺酮注射(30 mg/kg, 3次剂量),以评估ABA2期间氯胺酮的急性效应,以及10-13天后ABA3期间氯胺酮持续疗效的潜力。其余28只在ABA2 (CON)期间接受载体注射或不接受注射。结果:在ABA3期间,89%的CON患者观察到严重体重减轻(基线的20%),而只有69%的KET患者观察到严重体重减轻。在整个ABA2过程中,包括食物可用时间在内,KET组每天的总车轮运行量显著低于CON组(p < 0.01),并且这种减少持续到ABA3。氯胺酮对食物摄入没有显著影响。讨论:这些发现表明氯胺酮可能降低成年女性对ABA的易感,并可能通过减少多动症来保护女性免于AN复发。
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引用次数: 0
Neuroprotective Effect of Curcumin-Metavanadate in the Hippocampus of Aged Rats. 姜黄素对老年大鼠海马的神经保护作用。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1002/syn.70008
Sonia Irais Gonzalez-Cano, Ulises Peña-Rosas, Guadalupe Muñoz-Arenas, Diana Milena Torres-Cinfuentes, Samuel Treviño, Carolina Moran-Raya, Gonzalo Flores, Jorge Guevara, Alfonso Diaz

Brain aging is a multifactorial process that includes a reduction in the biological and metabolic activity of individuals. Oxidative stress and inflammatory processes are characteristic of brain aging. Given the current problems, the need arises to implement new therapeutic approaches. Polyoxidovanadates (POV), as well as curcumin, have stood out for their participation in a variety of biological activities. This work aimed to evaluate the coupling of metavanadate and curcumin (Cuma-MV) on learning, memory, redox balance, neuroinflammation, and cell death in the hippocampal region (CA1 and CA3) and dentate gyrus (DG) of aged rats. Rats 18 months old were administered a daily dose of curcumin (Cuma), sodium metavanadate (MV), or Cuma-MV for two months. The results demonstrated that administration of Cuma-MV for 60 days in aged rats improved short- and long-term recognition memory, decreased reactive oxygen species, and substantially improved lipoperoxidation in the hippocampus. Furthermore, the activity of superoxide dismutase and catalase increased in animals treated with Cuma-MV. It is important to highlight that the treatment with Cuma-MV exhibited a significantly greater effect than the treatments with MV or Cuma in all the parameters evaluated. Finally, we conclude that Cuma-MV represents a potential therapeutic option in the prevention and treatment of cognitive decline associated with aging.

大脑衰老是一个多因素过程,包括个体生物和代谢活动的减少。氧化应激和炎症过程是大脑衰老的特征。鉴于目前的问题,需要实施新的治疗方法。多氧化钒酸盐(Polyoxidovanadates, POV)和姜黄素因其参与多种生物活性而备受关注。本研究旨在评价元氰酸盐和姜黄素(Cuma-MV)偶联对老年大鼠海马区(CA1和CA3)和齿状回(DG)学习、记忆、氧化还原平衡、神经炎症和细胞死亡的影响。18个月大的大鼠每天服用姜黄素(Cuma)、偏氰酸钠(MV)或Cuma-MV,持续两个月。结果表明,老年大鼠服用Cuma-MV 60天可改善短期和长期识别记忆,减少活性氧,并显著改善海马脂质过氧化。此外,Cuma-MV处理动物的超氧化物歧化酶和过氧化氢酶活性增加。值得强调的是,在所有评估的参数中,使用Cuma-MV治疗的效果明显大于使用MV或Cuma治疗。最后,我们得出结论,Cuma-MV代表了预防和治疗与衰老相关的认知能力下降的潜在治疗选择。
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引用次数: 0
Measuring Alcohol-Induced Striatal Dopamine Release in Healthy Humans With [11C]-Raclopride: A Meta-Analysis. 用[11C]-Raclopride测量健康人酒精诱导的纹状体多巴胺释放:一项荟萃分析
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1002/syn.70007
Amir Kania, Natasha Porco, Fernando Caravaggio

Alcohol consumption is known to affect dopamine (DA) release in the brain, with significant implications for understanding addiction and its neurobiological underpinnings. This meta-analysis examined the effects of acute alcohol administration on striatal DA release in healthy humans as measured with [11C]-raclopride positron emission tomography (PET). Oral alcohol administration was associated with a significant reduction in [11C]-raclopride binding potential (BPND) in the ventral striatum (Cohen's d = -0.76), indicative of increased DA release, particularly at lower blood alcohol concentration (BAC) levels (0.08 gm%; Z = 2.34, p = 0.02). That oral alcohol may increase DA release in the ventral striatum at lower doses, and decrease DA release at higher doses, warrants further investigation but appears consistent with other known biphasic, hermetic dose-response effects of alcohol. Additionally, larger effect-sizes in the ventral striatum were observed among those studies which sampled more males than females (Z = -2.08, p = 0.04). While oral alcohol administration was associated with reduced [11C]-raclopride BPND in the caudate (Cohen's d = -0.39) and putamen (Cohen's d = -0.37), these findings in the dorsal striatum were more variable and less robust. Our analyses suggests that study design (i.e., counterbalanced versus fixed order) may moderate effect sizes observed in the putamen across studies (Z = -2.27, p = 0.02). By identifying gaps in the current literature and proposing directions for future research, this study hopes to inform the design of future PET studies aimed at quantifying alcohol-induced dopamine release in the striatum of humans.

众所周知,饮酒会影响大脑中多巴胺(DA)的释放,这对理解成瘾及其神经生物学基础具有重要意义。本荟萃分析通过[11C]-raclopride正电子发射断层扫描(PET)检测急性酒精给药对健康人纹状体DA释放的影响。口服酒精与腹侧纹状体[11C]-氯氯pride结合电位(BPND)显著降低相关(Cohen’s d = -0.76),表明DA释放增加,特别是在血液酒精浓度(BAC)水平较低时(0.08 gm%;Z = 2.34, p = 0.02)。口服酒精可能在低剂量时增加腹侧纹状体的DA释放,而在高剂量时减少DA释放,这值得进一步研究,但似乎与其他已知的双相、密闭的酒精剂量-反应效应一致。此外,在男性多于女性的研究中,腹侧纹状体的效应量更大(Z = -2.08, p = 0.04)。虽然口服酒精与尾状体(Cohen’s d = -0.39)和壳核(Cohen’s d = -0.37)中[11C]-raclopride BPND的减少有关,但背纹状体的这些发现更不稳定,也不那么有力。我们的分析表明,研究设计(即平衡与固定顺序)可能会调节各组研究中壳核观察到的效应大小(Z = -2.27, p = 0.02)。通过确定当前文献中的空白并提出未来的研究方向,本研究希望为未来旨在量化人类纹状体中酒精诱导的多巴胺释放的PET研究的设计提供信息。
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引用次数: 0
Correction to "[11C]PBB3 binding in Aβ(-) or Aβ(+) corticobasal syndrome". 修正“[11C]PBB3在Aβ(-)或Aβ(+)皮质基底综合征中的结合”。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2025-01-01 DOI: 10.1002/syn.70006
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引用次数: 0
Harnessing Miniscope Imaging in Freely Moving Animals to Unveil Migraine Pathophysiology and Validate Novel Therapeutic Strategies. 利用可自由移动动物的微型显微镜成像揭示偏头痛病理生理学并验证新型治疗策略。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1002/syn.70001
Caroline Degel, Kevin Zitelli, Jonathan Zapata, Jonathan Nassi, Paolo Botta

Migraine is a debilitating neurological disorder that affects millions worldwide. Elucidating its underlying mechanisms is crucial for developing effective therapeutic interventions. In this editorial, we discuss the potential applications of one-photon miniscopes, which enable minimally invasive, high spatiotemporal resolution fluorescence imaging in freely moving animals. By providing real-time visualization of vascular dynamics and neuronal activity, these cutting-edge techniques can offer unique insights into migraine pathophysiology. We explore the significance of these applications in preclinical research with a case study demonstrating their potential to drive the development of novel therapeutic strategies for effective migraine management.

偏头痛是一种使人衰弱的神经系统疾病,影响着全球数百万人。阐明其潜在机制对于开发有效的治疗干预措施至关重要。在这篇社论中,我们讨论了单光子微型显微镜的潜在应用,这种显微镜可对自由活动的动物进行微创、高时空分辨率的荧光成像。通过提供血管动态和神经元活动的实时可视化,这些尖端技术可以为偏头痛的病理生理学提供独特的见解。我们通过一个案例研究探讨了这些应用在临床前研究中的意义,并展示了它们在推动开发新型治疗策略以有效控制偏头痛方面的潜力。
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引用次数: 0
ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic ERK1/2 通过调节 DRP1 介导的线粒体动态来调控癫痫发作
IF 2.3 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-09-17 DOI: 10.1002/syn.22309
Ting Chen, Juan Yang, Yongsu Zheng, Xuejiao Zhou, Hao Huang, Haiqing Zhang, Zucai Xu
After seizures, the hyperactivation of extracellular signal‐regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin‐related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl‐Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi‐1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi‐1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p‐DRP1‐Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p‐DRP1‐Ser616 expression, which could inhibit DRP1‐mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.
癫痫发作后,细胞外信号调节激酶(ERK1/2)过度激活会导致线粒体功能障碍。通过达纳明相关蛋白 1(DRP1)的引导,ERK1/2 在多种疾病的发病机制中发挥作用。在此,我们推测ERK1/2会影响线粒体分裂,并通过调节DRP1的活性参与癫痫的发病机制。本研究通过腹腔注射氯化锂建立了大鼠癫痫状态(SE)模型。在诱导 SE 之前,腹腔注射 PD98059 和 Mdivi-1。然后监测发作次数和首次发作前的潜伏期。此外,还采用 Western 印迹法测定了大鼠海马中磷酸化和总 ERK1/2 及 DRP1 蛋白的表达水平。此外,免疫组化显示了 ERK1/2 和 DRP1 在海马 CA1 和 CA3 神经元中的分布。根据行为学研究结果,PD98059和Mdivi-1都能降低大鼠对癫痫发作的易感性。通过抑制 ERK1/2 磷酸化,Western 印迹显示 PD98059 间接降低了 DRP1 在 Ser616 的磷酸化(p-DRP1-Ser616)。通过免疫组化,ERK1/2和DRP1最终分布在神经元的细胞质中。抑制ERK1/2信号通路可下调p-DRP1-Ser616的表达,从而抑制DRP1介导的线粒体过度裂变,进而调控癫痫的发病机制。
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引用次数: 0
Calsyntenin-1 expression and function in brain tissue of lithium-pilocarpine rat seizure models. 锂-匹罗卡品大鼠癫痫模型脑组织中 Calsyntenin-1 的表达和功能。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-09-01 DOI: 10.1002/syn.22307
Fu Zhou, Rong Hu, Yuzhu Wang, Xiaohui Wu, Xuan Chen, Zhiqin Xi, Kebin Zeng

To present the expression of calsyntenin-1 (Clstn1) in the brain and investigate the potential mechanism of Clstn1 in lithium-pilocarpine rat seizure models. Thirty-five male SD adult rats were induced to have seizures by intraperitoneal injection of lithium chloride pilocarpine. Rats exhibiting spontaneous seizures were divided into the epilepsy (EP) group (n = 15), whereas those without seizures were divided into the control group (n = 14). Evaluate the expression of Clstn1 in the temporal lobe of two groups using Western blotting, immunohistochemistry, and immunofluorescence. Additionally, 55 male SD rats were subjected to status epilepticus (SE) using the same induction method. Rats experiencing seizures exceeding Racine's level 4 (n = 48) were randomly divided into three groups: SE, SE + control lentivirus (lentiviral vector expressing green fluorescent protein [LV-GFP]), and SE + Clstn1-targeted RNA interference lentivirus (LV-Clstn1-RNAi). The LV-GFP group served as a control for the lentiviral vector, whereas the LV-Clstn1-RNAi group received a lentivirus designed to silence Clstn1 expression. These lentiviral treatments were administered via hippocampal stereotactic injection 2 days after SE induction. Seven days after SE, Western blot analysis was performed to evaluate the expression of Clstn1 in the hippocampus and temporal lobe. Meanwhile, we observed the latency of spontaneous seizures and the frequency of spontaneous seizures within 8 weeks among the three groups. The expression of Clstn1 in the cortex and hippocampus of the EP group was significantly increased compared to the control group (p < .05). Immunohistochemistry and immunofluorescence showed that Clstn1 was widely distributed in the cerebral cortex and hippocampus of rats, and colocalization analysis revealed that it was mainly co expressed with neurons in the cytoplasm. Compared with the SE group (11.80 ± 2.17 days) and the SE + GFP group (12.40 ± 1.67 days), there was a statistically significant difference (p < .05) in the latency period of spontaneous seizures (15.14 ± 2.41 days) in the SE + Clstn1 + RNAi group rats. Compared with the SE group (4.60 ± 1.67 times) and the SE + GFP group (4.80 ± 2.05 times), the SE + Clstn1 + RNAi group (2.0 ± .89 times) showed a significant reduction in the frequency of spontaneous seizures within 2 weeks of chronic phase in rats (p < .05). Elevated Clstn1 expression in EP group suggests its role in EP onset. Targeting Clstn1 may be a potential therapeutic approach for EP management.

介绍钙调蛋白-1(Clstn1)在大脑中的表达,并研究Clstn1在氯化锂-皮洛卡品大鼠癫痫模型中的潜在机制。通过腹腔注射氯化锂皮洛卡品诱导35只雄性SD成年大鼠癫痫发作。表现为自发性癫痫发作的大鼠被分为癫痫(EP)组(n = 15),而没有癫痫发作的大鼠被分为对照组(n = 14)。使用 Western 印迹、免疫组织化学和免疫荧光评估两组大鼠颞叶中 Clstn1 的表达。此外,采用相同的诱导方法对 55 只雄性 SD 大鼠进行癫痫状态(SE)诱导。将癫痫发作超过拉辛4级的大鼠(n = 48)随机分为三组:SE、SE + 对照慢病毒(表达绿色荧光蛋白 [LV-GFP] 的慢病毒载体)和 SE + Clstn1 靶向 RNA 干扰慢病毒(LV-Clstn1-RNAi)。LV-GFP 组是慢病毒载体的对照组,而 LV-Clstn1-RNAi 组则接受了旨在抑制 Clstn1 表达的慢病毒。这些慢病毒治疗是在诱导 SE 2 天后通过海马立体定向注射进行的。SE七天后,我们进行了Western印迹分析,以评估Clstn1在海马和颞叶中的表达。同时,我们观察了三组患者自发癫痫发作的潜伏期和8周内自发癫痫发作的频率。与对照组相比,EP 组大脑皮层和海马中 Clstn1 的表达明显增加(p
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引用次数: 0
High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines. 高强度 AMPAkines 可诱导皮质神经元中 Gq 蛋白偶联的内质钙释放:解释高强度 AMPAkines 毒性的可能机制。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-09-01 DOI: 10.1002/syn.22310
Daniel P Radin, Sheng Zhong, Rok Cerne, Jeffrey M Witkin, Arnold Lippa

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase Cβ-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.

α-氨基-3-羟基-5-甲基-4-异噁唑丙酸受体(AMPAR)正异构调节剂(AMPAkines)具有许多有前途的治疗特性。然而,由于钙依赖性神经元毒性和体内抽搐的出现,高影响 AMPAkines 的药物开发受到了限制。而在浓度特别高的低浓度 AMPAkines 中却没有观察到这种毒性。由于大多数 AMPAR 对钙具有一定的不渗透性,本研究试图探讨在高浓度安巴碱存在时,不同机制对细胞内钙升高的影响程度。在仅有 AMPA 存在的情况下,细胞膜钙的升高表现为钠依赖性。然而,在环噻嗪(CTZ)或 CX614 等高活性 AMPA 碱的作用下,AMPAR 的增效还激活了另一种机制,促使钙从内质网(ER)贮存中释放出来。连接 AMPAR 与 ER 系统的途径包括 Gq 蛋白、磷脂酶 Cβ 介导的三磷酸肌醇(InsP3)形成,以及最终刺激位于 ER 上的 InsP3 受体。使用高浓度的低影响 AMPAkines、CX516(Ampalex)和 CX717 并未观察到相同的联系。我们还证明,CX614 在治疗剂量下会产生神经元过度兴奋,而新一代低影响 AMPAkine CX1739 在超高剂量下是安全的。尽管早先的研究已经证明了 AMPAR 与 G 蛋白之间的功能联系,但本报告表明,在高冲击 AMPAkine 的作用下,AMPAR 也会与 Gq 蛋白耦合,从而引发ER 的二次钙释放,这也让我们对高冲击和低冲击 AMPAkine 的不同作用有了更深入的了解。
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引用次数: 0
microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11. microRNA-125b-5p通过靶向SOX11缓解CCI诱导的神经病理性疼痛并调节神经炎症。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-09-01 DOI: 10.1002/syn.22306
Liping Wang, Bei Wang, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Haining Zhen

Background: Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP.

Methods: NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting.

Results: Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p.

Conclusion: miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.

背景:越来越多的证据表明,微RNA(miRNA)参与了神经病理性疼痛(NP)的发生和发展。探索神经病理性疼痛的分子机制并确定关键分子可为治疗神经病理性疼痛提供潜在靶点。本研究对miR-125b-5p调控NP的功能和机制进行了研究,旨在寻找NP的潜在治疗靶点:方法:采用慢性收缩损伤(CCI)法建立 NP 大鼠模型。方法:采用慢性收缩性损伤(CCI)方法建立 NP 大鼠模型,评估大鼠爪退缩阈值和爪退缩潜伏期,以评价大鼠的建立和恢复情况。用脂多糖(LPS)处理大鼠小胶质细胞系--高侵袭性增殖永生(HAPI)小胶质细胞。通过酶联免疫吸附试验和免疫印迹法对 M1/M2 极化和炎症进行了评估:结果:在CCI大鼠和LPS诱导的HAPI细胞中观察到miR-125b-5p减少和SOX11增加。过表达 miR-125b-5p 可减轻 CCI 大鼠的机械异感和热痛,并抑制炎症。miR-125b-5p能负向调节SOX11在CCI大鼠和LPS诱导的HAPI细胞中的表达。结论:miR-125b-5p 通过负向调节 SOX11 来调节炎症和小胶质细胞的极化,从而对 NP 起保护作用。
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引用次数: 0
Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine. 氟西汀对小龙虾运动轴突动作电位的抑制性调节。
IF 1.6 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-07-01 DOI: 10.1002/syn.22304
Selene Wang, Si Seng Lam, Anisah Aguilar, Stephanie Anakwe, Katherine Barahona, Hani Haider, Olivia Hunyadi, Kaahini Jain, Derek Kolodziejski, Anindita Lal, Man Li, Frank MacKenzie, John Miller, Oliviero Nardin, Emily Nguyen, Jaii Pappu, Melissa Rodriguez, Jen-Wei Lin

The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.

本报告旨在利用小龙虾腹侧浅屈肌制备方法,探讨 K2P 通道如何调节轴突兴奋性。这种制备方法可同时记录来自肌纤维的运动神经胞外动作电位(eAP)和胞内兴奋交界电位(EJP)。之前的药理学研究已经证明了小龙虾体内存在 K2P 样通道。本研究使用氟西汀(50 µM)阻断 K2P 通道。阻断剂导致运动轴突动作电位逐渐下降,最终完全阻断。在阻滞的中间阶段,当 eAP 的峰-峰振幅下降到对照值的∼60%-80% 时,eAP 初始正分量的振幅下降速度快于代表钠流入的负峰值。此外,钠流入后的第二个正峰值(对应于细胞内记录的动作电位(iAP)的超极化后阶段)在 eAP 阻滞的中间阶段变得更大。最后,与 eAP 同时记录的 EJP 在振幅上没有变化,但在突触延迟上有显著增加。eAP 形状和 EJP 延迟的这些变化被解释为 K2P 通道阻滞后静息膜电位去极化的结果。除了深入了解 K2P 通道在无髓鞘轴突中可能发挥的功能外,本文介绍的结果还可作为一个实例,说明 eAP 形状的变化所包含的信息可用于推断细胞内事件的改变。这种 eAP-iAP 交叉推论对于深入了解这里的机理很有价值,也可能适用于其他模型系统。
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Synapse
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