Neuroscience Letters最新文献_第8页

Mini-review: “Hippocalcin: Molecular mechanisms and therapeutic potential in neuronal function” 迷你综述：“希波calcin：神经元功能的分子机制和治疗潜力”。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-20 DOI: 10.1016/j.neulet.2025.138427

Shin-Young Park

Hippocalcin (HPCA), a neuronal Ca²⁺ sensor protein in the EF-hand superfamily, plays a key role in calcium signaling and neurological function in the central nervous system. This review highlights HPCA’s structure–function relationships and clinical significance. Through Ca2⁺-dependent conformational changes and a unique calcium-myristoyl switch, HPCA dynamically associates with membranes, acting as both sensor and effector. It modulates neuronal excitability, synaptic plasticity, neurodevelopment, and neuroprotection. Notably, HPCA is critical in mediating slow afterhyperpolarization, a key mechanism for adjusting neuronal firing patterns and maintaining excitability homeostasis. It also influences neural stem cell fate by promoting neuronal differentiation and suppressing astrocytic differentiation. HPCA maintains mitochondrial calcium homeostasis and activates survival pathways, protecting against apoptosis and oxidative stress. Its dysregulation is implicated in Alzheimer’s and Parkinson’s diseases, epilepsy, depression, schizophrenia, and dystonia. Given its restricted expression in the brain and multifaceted functional roles, further elucidation of HPCA-mediated signaling mechanisms is warranted to advance the development of targeted therapeutic strategies for a broad spectrum of neurological disorders.

Hippocalcin （HPCA）是EF-hand超家族中的一种神经元Ca2+传感器蛋白，在中枢神经系统的钙信号传导和神经功能中起关键作用。本文综述了HPCA的结构功能关系及其临床意义。通过Ca2+依赖的构象变化和独特的肉豆蔻酰基钙开关，HPCA动态地与膜结合，同时作为传感器和效应器。它调节神经元兴奋性、突触可塑性、神经发育和神经保护。值得注意的是，HPCA在调节神经元放电模式和维持兴奋性稳态的关键机制——慢后超极化中起着关键作用。它还通过促进神经元分化和抑制星形细胞分化来影响神经干细胞的命运。HPCA维持线粒体钙稳态，激活生存途径，防止细胞凋亡和氧化应激。它的失调与阿尔茨海默病、帕金森病、癫痫、抑郁症、精神分裂症和肌张力障碍有关。鉴于其在大脑中的限制性表达和多方面的功能作用，进一步阐明hca介导的信号机制是有必要的，以促进针对广泛神经系统疾病的靶向治疗策略的发展。

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引用次数: 0

Combined chronic oral methylphenidate and fluoxetine treatment increases CB1 receptor density in the somatosensory forelimb region 慢性口服哌甲酯和氟西汀联合治疗可增加躯体感觉前肢区域CB1受体密度。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-02 DOI: 10.1016/j.neulet.2025.138407

Abigail M. Lantry , Huy Lu , Matt Marion , John Hamilton , Brittany Richardson , Teresa Quattrin , Lucy D. Mastrandrea , Michael Hadjiargyrou , David Komatsu , Panayotis K. Thanos

Methylphenidate (MP) is a psychostimulant commonly prescribed for attention-deficit/hyperactivity disorder (ADHD), and Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed to treat depression and anxiety disorders. Both are shown to impact neurochemistry and behavior, but little is known about their individual and combined impacts on the endocannabinoid system (ECS). We examined the effects of MP and FLX, both as separate treatments and in combination, on cannabinoid receptor type 1 (CB1) binding in several key brain regions of interest. Male rats were treated with either water, MP, FLX, or MP + FLX via a previously established drinking paradigm for three months. Brains were harvested, and [³H] SR141716A in vitro autoradiography was performed to quantify CB1 binding. The combined treatment of MP + FLX showed significantly higher [³H] SR141716A binding compared to the water, MP, and FLX groups in the somatosensory forelimb (S(FL)) region. This indicates an ability of the common co-usage of MP and FLX to increase CB1 levels in the somatosensory cortex: a region of the brain required for the processing of sensory information.

哌醋甲酯（MP）是一种精神兴奋剂，通常用于治疗注意力缺陷多动障碍（ADHD），氟西汀（FLX）是一种血清素选择性再摄取抑制剂（SSRI），通常用于治疗抑郁症和焦虑症。两者都被证明会影响神经化学和行为，但对它们对内源性大麻素系统（ECS）的单独和联合影响知之甚少。我们研究了MP和FLX的作用，无论是单独治疗还是联合治疗，对大麻素受体1型（CB1）在几个关键脑区结合的影响。雄性大鼠分别用水、MP、FLX或MP + FLX通过先前建立的饮用模式治疗三个月。采集脑，对[3H] SR141716A进行体外放射自显影以定量CB1结合。与水、MP和FLX组相比，MP + FLX联合处理在体感觉前肢S（FL）区显示出更高的[3H] SR141716A结合。这表明MP和FLX的共同使用能够增加体感觉皮层（大脑中处理感觉信息所需的区域）中CB1的水平。

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引用次数: 0

Ferulic acid possesses anxiolytic activity: evidence for the involvement of serotonergic and noradrenergic systems 阿魏酸具有抗焦虑活性：证据涉及血清素能和去甲肾上腺素能系统。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-12 DOI: 10.1016/j.neulet.2025.138416

Ozlem Pınar Cetiner , Hazal Eken , Feyza Alyu Altınok , Rana Arslan , Nurcan Bektas

The current study aims to evaluate any potential anxiolytic effects and the action mechanisms of ferulic acid, a phenolic phytochemical compound, in mice. The anxiolytic activity of ferulic acid at the doses of 0.1, 1, 10, and 100 mg/kg, p.o in female BALB/c mice was assessed by open field, hole-board and elevated plus maze tests. The possible roles of noradrenergic, serotonergic, and GABAergic modulation in the anxiolytic action of 100 mg/kg ferulic acid were also investigated by pretreatment with 5 mg/kg (i.p.) yohimbine, 1 mg/kg (i.p.) WAY-100635, and 3 mg/kg (i.p.) flumazenil, respectively, in the hole-board and open field tests. Similar to the positive standard diazepam (1 mg/kg, i.p); without altering the locomotor activity, 100 mg/kg ferulic acid significantly altered all the parameters related to anxiolytic activity, whereas 0.1 and 10 mg/kg doses were found to be effective in only some parameters in elevated plus-maze and open field tests, suggesting a U-shaped dose–response pattern. The anxiolytic effect of 100 mg/kg ferulic acid was significantly antagonized by the pretreatment with 5-HT_1A receptor antagonist WAY-100635 and especially by α-2 adrenoceptor antagonist yohimbine while the anxiolytic action was not blocked by GABA_A/BZ receptor antagonist flumazenil pretreatment. The findings imply that ferulic acid’s anxiolytic effect is mediated by the activation of α-2 adrenoceptors and 5-HT_1A receptors. In conclusion, it is possible to say that ferulic acid can be a safe potential agent which that be used alone or in combination with current effective treatments for anxiety.

本研究旨在评价阿魏酸（一种酚类植物化合物）对小鼠的潜在抗焦虑作用及其作用机制。采用开场、孔板、升高加迷宫试验，评价0.1、1、10、100 mg/kg, p.o剂量阿魏酸对BALB/c雌性小鼠的抗焦虑活性。用5 mg/kg （i.p.）育亨宾和1 mg/kg （i.p.）预处理阿魏酸，探讨去甲肾上腺素能、血清素能和gaba能调节在100 mg/kg阿魏酸抗焦虑作用中的可能作用。WAY-100635和3 mg/kg （i.p.）氟马西尼，分别在孔板试验和露天试验中。与阳性标准地西泮相似（1 mg/kg, i.p）；在不改变运动活性的情况下，100 mg/kg阿威酸显著改变了与焦虑活性相关的所有参数，而0.1和10 mg/kg阿威酸仅对部分参数有效，提示u型剂量-反应模式。100 mg/kg阿魏酸的抗焦虑作用可被5-HT1A受体拮抗剂WAY-100635和α-2肾上腺素受体拮抗剂育亨宾显著拮抗，而GABAA/BZ受体拮抗剂氟马西尼不阻断其抗焦虑作用。提示阿魏酸的抗焦虑作用是通过激活α-2肾上腺素受体和5-HT1A受体介导的。总之，可以说阿魏酸是一种安全的潜在药物，可以单独使用，也可以与目前有效的治疗焦虑症的药物联合使用。

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引用次数: 0

Insulin-regulated aminopeptidase inhibitor C9 restores cellular activity in methadone-damaged primary cell cultures 胰岛素调节的氨基肽酶抑制剂C9在美沙酮损伤的原代细胞培养中恢复细胞活性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-10 DOI: 10.1016/j.neulet.2025.138415

Frida Stam , Sara Bjurling , Erik Nylander , Esther Olaniran Håkansson , Johan Gising , Mats Larhed , Luke R. Odell , Alfhild Grönbladh , Mathias Hallberg

Insulin-regulated aminopeptidase (IRAP) is emerging as a pharmaceutical target for treatment of neurotoxic- and neurodegenerative symptoms commonly seen in cognitive impairments. Ligands of IRAP, such as Angiotensin IV and similar analogues, bind to the active site of IRAP and causes an inhibition of its enzymatic activity, which is suggested to improve cognitive functions. Opioids are widely used in the clinic to treat for example pain and opioid use disorder, however opioid use have been associated with cognitive impairments, impaired neuronal development, and neuronal damage. To evaluate the potential of the macrocyclic IRAP inhibitor compound 9 (C9), the present study examined the restorative effects of C9 after opioid-induced cell toxicity. The toxic impact of the commonly used opioids methadone and buprenorphine was determined in rat primary hippocampal and cortical cells, along with the effects on various viability markers after subsequent treatment with C9. The metabolism of tetrazolium bromide salt (MTT) was measured to assess mitochondrial activity, and the level of membrane damage was assessed by measuring lactate dehydrogenase (LDH) in the cell media. Fluorescent calcein dye was used to evaluate intracellular esterase activity. In conclusion, this study demonstrate that methadone and buprenorphine induce toxic effects in primary hippocampal and cortical cell cultures and that IRAP inhibitor C9 has a restorative effect on intracellular esterase activity in methadone-damaged cells.

胰岛素调节氨基肽酶（IRAP）正在成为治疗认知障碍中常见的神经毒性和神经退行性症状的药物靶点。IRAP的配体，如血管紧张素IV和类似的类似物，结合到IRAP的活性位点并抑制其酶活性，这被认为可以改善认知功能。阿片类药物在临床上被广泛用于治疗疼痛和阿片类药物使用障碍，然而阿片类药物的使用与认知障碍、神经元发育受损和神经元损伤有关。为了评估大环IRAP抑制剂化合物9 （C9）的潜力，本研究检测了C9在阿片类药物诱导的细胞毒性后的恢复作用。研究了常用阿片类药物美沙酮和丁丙诺啡对大鼠海马和皮质细胞的毒性作用，以及C9后续治疗对各种活力指标的影响。通过测定四氮唑溴化盐（MTT）代谢来评估线粒体活性，通过测定细胞培养基中的乳酸脱氢酶（LDH）来评估膜损伤水平。荧光钙黄蛋白染色法测定细胞内酯酶活性。总之，本研究表明，美沙酮和丁丙诺啡在原代海马和皮质细胞培养中诱导毒性作用，并且IRAP抑制剂C9对美沙酮损伤细胞的细胞内酯酶活性具有恢复作用。

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引用次数: 0

Site-Specific Regulation of Tau phosphorylation by MAPK pathways during HFS-Induced synaptic plasticity in the Rat hippocampus hfs诱导大鼠海马突触可塑性过程中MAPK通路对Tau磷酸化的位点特异性调控。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-21 DOI: 10.1016/j.neulet.2025.138426

Cem Süer, Burak Tan, Nurcan Dursun, Bilal Koşar, Ercan Babur

This study examined the role of MAPKs in Tau phosphorylation and synaptic plasticity at perforant pathway–dentate gyrus (PP–DG) synapses following high-frequency stimulation (HFS). In vivo experiments were conducted on adult male Wistar rats under urethane anesthesia. Field potentials (fEPSP and PS) were recorded in the DG granule cell layer in response to PP stimulation. Western blotting assessed total and phosphorylated levels of Tau, ERK1/2, JNK, and P38 MAPK in HFS-induced hippocampus. MAPK inhibition disrupted early somatic potentiation when applied during induction, and JNK inhibition alone impaired late potentiation. Reduced somatic activity correlated with decreased MAPK phosphorylation and Tau phosphorylation at Ser422. Findings suggest that ERK1/2, JNK, and P38 are essential for Tau phosphorylation at Ser422 in HFS-induced hippocampal synapses.

本研究探讨了MAPKs在高频刺激（HFS）后穿孔通路-齿状回（PP-DG）突触Tau磷酸化和突触可塑性中的作用。以成年雄性Wistar大鼠为实验对象，在氨基甲酸乙酯麻醉下进行体内实验。在PP刺激下记录DG颗粒细胞层的场电位（fEPSP和PS）。Western blotting检测hfs诱导海马中Tau、ERK1/2、JNK和P38 MAPK的总水平和磷酸化水平。当在诱导过程中应用MAPK抑制时，会破坏早期体细胞增强，而JNK单独抑制会破坏晚期增强。体细胞活性降低与MAPK磷酸化和Tau蛋白Ser422磷酸化降低相关。研究结果表明，ERK1/2、JNK和P38对于hfs诱导的海马突触Ser422位点的Tau磷酸化至关重要。

引用次数: 0

Acute exposure to vaporized cannabidiol remodels coding and noncoding transcriptomes in the mouse striatum 急性暴露于汽化大麻二酚重塑编码和非编码转录组在小鼠纹状体。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-26 DOI: 10.1016/j.neulet.2025.138428

Mi Ran Choi , Chaeeun Park , Jihun Kim , Jeong-Hyeon Heo , Seok Hwan Chang , Han-Na Kim , Yeung Bae Jin , Sang-Rae Lee

Cannabidiol (CBD) is increasingly consumed via vaping, but its acute molecular impact on the striatum, a critical hub for motor control and reward processing that is highly sensitive to cannabinoid modulation, remains poorly understood. This study investigated differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the striatum after acute exposure to vaporized CBD. Male ICR mice (n = 5 per group) were exposed to vaporized CBD oil (50 mg) and striatal tissues were collected 24 h later. Differentially expressed mRNAs and lncRNAs were identified using total RNA sequencing and mRNA–lncRNA co-expression networks were constructed. Selected transcripts were validated using qRT-PCR and discriminative capacity was assessed by ROC analysis. CBD exposure altered the expression of 931 mRNAs and 229 lncRNAs. GO and KEGG analyses revealed bidirectional regulation of pathways involved in neural development and synaptic transmission, including both up- and downregulated genes in categories such as glutamatergic synapse. Ion transport genes (Trpm2, Tmem63a, Tmem175, Glrb) were robustly upregulated, while genes involved in excitatory synaptic structure (Dlgap2, Shisa9, Tac1) and dopaminergic-associated pathways (Drd3, Oxt) were downregulated. mRNA–lncRNA network analysis highlighted regulatory hubs including NONMMUT114016.1 and NONMMUT057055.2, and ROC analysis identified strong biomarker candidates such as Tmem175, Ptprd, NONMMUT042895.2, and NONMMUT151847.1. These findings indicate that acute CBD vaping induces widespread transcriptomic remodeling in the striatum, enhancing ion transport and inhibitory signaling while suppressing excitatory and dopaminergic pathways. This study provides the first comprehensive striatal transcriptome profiling of coding and noncoding RNAs in response to vaporized CBD.

大麻二酚（CBD）越来越多地通过电子烟消耗，但其对纹状体的急性分子影响仍然知之甚少，纹状体是运动控制和奖励处理的关键枢纽，对大麻素调节高度敏感。本研究研究了急性暴露于汽化CBD后纹状体中长链非编码rna （lncRNAs）和mrna的差异表达。雄性ICR小鼠（n = 每组5只）暴露于蒸发的CBD油（50 mg）， 24 h后收集纹状体组织。利用总RNA测序技术鉴定差异表达mrna和lncrna，构建mRNA-lncRNA共表达网络。选取的转录本采用qRT-PCR验证，并采用ROC分析评估其鉴别能力。CBD暴露改变了931个mrna和229个lncrna的表达。GO和KEGG分析揭示了参与神经发育和突触传递的双向调控通路，包括谷氨酸突触等类别的上调和下调基因。离子转运基因（Trpm2、Tmem63a、Tmem175、Glrb）显著上调，而参与兴奋性突触结构的基因（dgap2、Shisa9、Tac1）和多巴胺能相关通路（Drd3、Oxt）下调。mRNA-lncRNA网络分析突出了调控枢纽，包括NONMMUT114016.1和NONMMUT057055.2， ROC分析确定了强有力的生物标志物候选，如Tmem175、Ptprd、NONMMUT042895.2和NONMMUT151847.1。这些发现表明，急性CBD雾化诱导纹状体广泛的转录组重塑，增强离子运输和抑制信号传导，同时抑制兴奋和多巴胺能通路。这项研究提供了第一个全面的纹状体转录组分析编码和非编码rna对汽化CBD的反应。

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引用次数: 0

From stress to Alzheimer’s: A circuit-based framework for prefrontal cognitive dysfunction 从压力到阿尔茨海默病：前额叶认知功能障碍的电路基础框架

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-18 DOI: 10.1016/j.neulet.2025.138424

Jee Hyun Yi

Impairments in working memory and cognitive flexibility are early and consistent features of both Alzheimer’s disease (AD) and stress. These functions depend critically on prefrontal cortical (PFC) circuits, which are particularly vulnerable to neuromodulatory and pathological insults. Recent studies suggest that stress and AD do not simply act globally, but instead converge on specific molecular and cellular targets within distinct neural populations. Notably, both chronic stress and Alzheimer’s disease models exhibit dysregulation of synaptic signaling via NR2B-containing NMDA receptors and aberrant GSK-3β activation. These changes often emerge in a cell-type-specific manner, affecting excitatory pyramidal neurons and vulnerable interneuron subtypes such as SST+, PV+, and VIP + cells. The resulting imbalance in excitation and inhibition disrupts the integrity of prefrontal circuits, impairing adaptive behavior. This review synthesizes evidence across molecular, cellular, and circuit levels to outline a framework in which stress and AD pathology converge on shared vulnerable pathways. Understanding how specific cell populations mediate this vulnerability may lead to targeted strategies for enhancing cognitive resilience in neurodegenerative and stress-related disorders.

工作记忆和认知灵活性的损伤是阿尔茨海默病（AD）和压力的早期和一致特征。这些功能主要依赖于前额皮质（PFC）回路，该回路特别容易受到神经调节和病理损伤。最近的研究表明，压力和AD并不是简单地在全球范围内起作用，而是集中在不同神经群体中的特定分子和细胞目标上。值得注意的是，慢性应激和阿尔茨海默病模型均表现出通过含有nr2b的NMDA受体和GSK-3β异常激活的突触信号失调。这些变化通常以细胞类型特异性的方式出现，影响兴奋性锥体神经元和脆弱的中间神经元亚型，如SST+、PV+和VIP +细胞。由此产生的兴奋和抑制的不平衡破坏了前额叶回路的完整性，损害了适应性行为。本综述综合了分子、细胞和神经回路水平的证据，概述了应激和AD病理在共同易感通路上趋同的框架。了解特定细胞群如何介导这种脆弱性可能会导致有针对性的策略，以增强神经退行性和压力相关疾病的认知弹性。

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引用次数: 0

Limitations of antibody-mediated neutrophil depletion in understanding the role of neutrophils following spinal cord injury in mice 抗体介导的中性粒细胞耗竭在了解小鼠脊髓损伤后中性粒细胞作用方面的局限性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-12-10 Epub Date: 2025-10-17 DOI: 10.1016/j.neulet.2025.138425

Rubing Zhou, Dawei Song, Miao Li, Hua Gao

The role of neutrophils in spinal cord injury (SCI) remains incompletely understood due to the absence of effective intervention strategies. Some studies employing antibody-mediated neutrophil depletion (ND) in vivo have yielded various conclusions. However, the mechanism of ND remains unclear, and a comprehensive assessment of its effects was largely lacking prior to application. In this study, we aimed to evaluate neutrophil-related changes following ND in SCI. Hematological analysis revealed that ND attenuated the SCI-induced rise in neutrophil counts but had a negligible effect on baseline levels. The level of IL-1β and IL-8 increased in plasma and intact spinal cord after ND, but exhibited divergent changes post-SCI. Tissue concentrations of TNF-α were elevated in the intact spinal cord but declined following SCI with ND. Neutrophil elastase, a neutrophil cytoplasm-specific protein, increased in both intact and injured spinal cord following ND. Furthermore, ND did not markedly affect SCI-induced blood-spinal cord barrier (BSCB) leakage. These findings indicate that antibody-mediated ND produces complicated effects, rendering it a suboptimal approach for studying neutrophils’ contributions in SCI pathophysiology. Conclusions derived from this method should be interpreted with caution, and alternative strategies should be pursued to better elucidate the role of neutrophils in SCI.

由于缺乏有效的干预策略，中性粒细胞在脊髓损伤（SCI）中的作用仍然不完全清楚。一些在体内使用抗体介导的中性粒细胞耗竭（ND）的研究已经得出了不同的结论。然而，ND的机制尚不清楚，在应用前对其效果的全面评估在很大程度上缺乏。在这项研究中，我们旨在评估脊髓损伤后中性粒细胞相关的变化。血液学分析显示ND可减弱sci诱导的中性粒细胞计数升高，但对基线水平的影响可以忽略不计。ND后血浆和完整脊髓中IL-1β和IL-8水平升高，但脊髓损伤后呈发散性变化。TNF-α的组织浓度在完整脊髓中升高，但在脊髓损伤合并ND后下降。中性粒细胞弹性蛋白酶，一种中性粒细胞细胞质特异性蛋白，在ND后完好和损伤的脊髓中均增加。此外，ND对sci诱导的血脊髓屏障（BSCB）渗漏无明显影响。这些发现表明，抗体介导的ND产生复杂的作用，因此它不是研究中性粒细胞在脊髓损伤病理生理中的作用的最佳方法。从该方法得出的结论应谨慎解释，并应寻求替代策略，以更好地阐明中性粒细胞在脊髓损伤中的作用。

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引用次数: 0

Cannabidiol engages the peripheral endogenous opioid system to produce analgesia in neuropathic mice 大麻二酚参与外周内源性阿片系统对神经病小鼠产生镇痛作用。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-09-27 DOI: 10.1016/j.neulet.2025.138393

Douglas Lamounier de Almeida , Walace Cássio Pinto Barra , Renata Cristina Mendes Ferreira , Flávia Cristina Fonseca , Daniel Portela Dias Machado , Danielle Diniz Aguiar , Francisco Silveira Guimaraes , Igor Dimitri Gama Duarte , Thiago Roberto Lima Romero

Cannabidiol (CBD) has been getting attention from the scientific community regarding its potential for the treatment of different conditions, such as epilepsy, anxiety, and pain. This potential can be useful in clinical practice as an alternative or as an adjuvant alongside conventional therapeutic approaches; however, its mechanisms of action should be best described for its more effective application. Thus, our study aimed to evaluate whether the peripheral opioid system is involved in the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain. Male Swiss mice were subjected to the sciatic constriction injury, and their nociceptive threshold was evaluated using the mechanical paw pressure test. Cannabidiol 20 mg/Kg produced an antinociceptive effect. Bestatin (400 µg/paw), a selective aminopeptidase-N inhibitor, potentiates the intermediate analgesic response of CBD at the dose of 2 mg/Kg. Naloxone (50 µg/paw), a non-selective opioid receptor antagonist, reversed the CBD-mediated analgesia. CTOP (5, 10, and 20 µg/paw) and naltrindole (30, 60, and 120 µg/paw), μ and Δ opioid receptor antagonists, but not norBNI (200 µg/paw), a κ opioid receptor antagonist, partially reversed the CBD analgesia. Thus, our study shows that cannabidiol may induce activation of opioid receptors in the periphery as a part of its analgesic mechanism in neuropathic pain.

大麻二酚（CBD）因其治疗癫痫、焦虑和疼痛等不同疾病的潜力而受到科学界的关注。这种潜力可以在临床实践中作为替代或辅助常规治疗方法；但是，为了更有效地应用它，最好描述它的作用机制。因此，我们的研究旨在评估外周阿片系统是否参与大麻二酚系统性治疗神经性疼痛的镇痛机制。雄性瑞士小鼠坐骨收缩损伤后，采用机械爪压试验评估损伤阈值。大麻二酚20 mg/Kg具有抗伤害感受作用。Bestatin（400 µg/paw）是一种选择性氨基肽酶- n抑制剂，在剂量为2 mg/Kg时可增强CBD的中间镇痛反应。非选择性阿片受体拮抗剂纳洛酮（50 µg/爪）逆转了cbd介导的镇痛作用。CTOP（5、10和20 µg/爪）和纳曲多（30、60和120 µg/爪），μ和Δ阿片受体拮抗剂，但κ阿片受体拮抗剂norBNI（200 µg/爪）不能部分逆转CBD镇痛。因此，我们的研究表明，大麻二酚可能诱导外周阿片受体的激活，作为其在神经性疼痛镇痛机制的一部分。

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引用次数: 0

Increased reactive oxygen species in the spinal cord drive renal sympathetic vasomotor activity in Goldblatt hypertensive rats Goldblatt高血压大鼠脊髓活性氧增加驱动肾交感血管舒张活性。

IF 2 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters

Pub Date : 2025-11-20 Epub Date: 2025-10-03 DOI: 10.1016/j.neulet.2025.138408

Fernanda M. Tagliapietra, Maycon I.O. Milanez, Edina da Luz Abreu, Erika E. Nishi, Cássia T. Bergamaschi, Ruy R. Campos

Increased production of reactive oxygen species (ROS) in brain regions contributes to the sympathetic vasomotor overactivity in Goldblatt hypertension (2K1C). Previously, studies reported that overexpression of spinal angiotensin II (Ang II) type I (AT1) contributes to sympathetic vasomotor overactivation in 2K1C rats. Considering that Ang II leads to an imbalance of oxidative stress, the present study evaluated the role of spinal ROS in regulating the activity of sympathetic preganglionic neurons in 2K1C rats. Hypertension was induced by clipping the left renal artery. Six weeks after clipping, a catheter was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of intrathecal (i.t.) injection of Tempol on mean arterial pressure (MAP), heart rate (HR), renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively) were evaluated over 60 consecutive minutes. mRNA expression of enzymes involved in oxidative balance was analyzed in the spinal cord. In addition, spinal ROS abundance was quantified by the DHE fluorescence method. An increase in ROS production was observed in the thoracic region of 2K1C rats compared to the control group. I.t. administration of Tempol triggered a significant and preferential reduction in rSNA in the 2K1C but not in control rats. Thus, the data suggest that renal sympathoexcitation in 2K1C rats was associated with an increase in oxidative imbalance in the spinal cord, particularly in sympathetic preganglionic neurons that drive rSNA.

脑区活性氧（ROS）的产生增加有助于Goldblatt高血压（2K1C）交感血管舒动过度活跃。先前的研究报道，脊髓血管紧张素II (Ang II) I型（AT1）的过度表达有助于2K1C大鼠交感血管舒缩过度激活。考虑到Ang II导致氧化应激失衡，本研究评估了脊髓ROS在调节2K1C大鼠交感神经节前神经元活性中的作用。左肾动脉夹持引起高血压。夹持6周后，将导管插入蛛网膜下腔并推进至尿道麻醉大鼠的T10-11椎体水平。观察连续60分钟鞘内注射Tempol对大鼠平均动脉压（MAP）、心率（HR）、肾脏和内脏交感神经活动（rSNA和sSNA）的影响。分析脊髓中参与氧化平衡的酶的mRNA表达。此外，用DHE荧光法定量脊髓ROS丰度。与对照组相比，在2K1C大鼠的胸部区域观察到ROS的产生增加。Tempol在2K1C大鼠中触发了显著的、优先的rSNA减少，但在对照大鼠中没有。因此，这些数据表明，2K1C大鼠的肾交感神经兴奋与脊髓氧化不平衡的增加有关，特别是在驱动rSNA的交感神经节前神经元中。

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