Neuropeptides最新文献_第6页

Transcranial pulsed current stimulation alleviates neuronal pyroptosis and neurological dysfunction following traumatic brain injury via the orexin-A/NLRP3 pathway 经颅脉冲电流刺激可通过orexin-A/NLRP3通路缓解外伤性脑损伤后神经元焦亡和神经功能障碍

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-01-04 DOI: 10.1016/j.npep.2025.102501

Peng Yao , Qianhui Zhou , Bingkai Ren , Li Yang , Yang Bai , Zhen Feng

Traumatic brain injury (TBI) is a life-threatening condition with high incidence and mortality rates. The current pharmacological interventions for TBI exhibit limited efficacy, underscoring the necessity to explore novel and effective therapeutic approaches to ameliorate its impact. Previous studies have indicated that transcranial pulsed current stimulation (tPCS) can improve neurofunctional deficits in patients by modulating brain neuroplasticity. However, the exact mechanism underlying this neuroprotective effect remains elusive. In this study, mice with TBI induced by controlled cortical impact were subjected to 30 min of daily tPCS for 5 consecutive days and intraperitoneally administered an orexin receptor type 1 (OX₁R) antagonist (SB334867). The neuroprotective effects of tPCS and its potential mechanisms were assessed through behavioral tests, histopathological examination, immunohistochemistry and Western blotting. In vitro experiments involved stimulating HT22 cells with LPS + ATP to assess the anti-neuroinflammatory effects of Orexin-A (OX-A) using CCK-8, Western blotting, and Flow cytometry. The results demonstrated that tPCS reduced the mNSS in TBI mice, ameliorated tissue damage, improved motor and cognitive deficits, and upregulated OX-A expression. Notably, SB334867 reversed the protective effects of tPCS. In vitro studies revealed that OX-A inhibited the formation and activation of NLRP3 inflammasomes, resulting in reduced levels of ROS and restoration of MMP. However, this effect could be reversed by the NLRP3 agonist BMS-986299. Our findings suggest that tPCS promotes the release of OX-A and modulates the OX₁R/NLRP3 pathway to mitigate the inflammatory response following TBI, thereby exerting neuroprotective effects.

外伤性脑损伤（TBI）是一种发病率高、死亡率高、危及生命的疾病。目前对创伤性脑损伤的药物干预显示出有限的疗效，这强调了探索新的有效治疗方法来改善其影响的必要性。先前的研究表明，经颅脉冲电流刺激（tPCS）可以通过调节脑神经可塑性来改善患者的神经功能缺陷。然而，这种神经保护作用的确切机制仍然难以捉摸。在这项研究中，由控制性皮质冲击诱导的TBI小鼠连续5天每天接受30分钟的tPCS，并腹腔注射食欲素受体1型（OX1R）拮抗剂（SB334867）。通过行为学试验、组织病理学检查、免疫组织化学和免疫印迹法评价tPCS的神经保护作用及其可能机制。体外实验采用CCK-8、Western blotting和流式细胞术，用LPS + ATP刺激HT22细胞，评估Orexin-A （OX-A）的抗神经炎作用。结果表明，tPCS可降低TBI小鼠的mNSS，改善组织损伤，改善运动和认知缺陷，上调OX-A表达。值得注意的是，SB334867逆转了tPCS的保护作用。体外研究表明，OX-A抑制NLRP3炎性小体的形成和激活，导致ROS水平降低，MMP恢复。然而，这种作用可以被NLRP3激动剂BMS-986299逆转。我们的研究结果表明，tPCS促进OX-A的释放并调节OX1R/NLRP3通路，从而减轻TBI后的炎症反应，从而发挥神经保护作用。

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引用次数: 0

The impact of endogenous N/OFQ on DPN: Insights into lower limb blood flow regulation in rats 内源性N/OFQ对DPN的影响：对大鼠下肢血流调节的研究

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-01-01 DOI: 10.1016/j.npep.2024.102492

Yuan-jing Qin , Po Zhang , Peng Zhang , Jing Li , Qixing Yang , Jun-li Sun , Yu-zhang Liang , Li-li Wang , Lin-zhong Zhang , Yi Han

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, often accompanied by impaired vascular endothelial function in the lower limbs. This dysfunction is characterized by a reduced vasodilatory response, leading to decreased blood flow in the lower limbs and ultimately contributing to the development of diabetic peripheral neuropathy. To delve deeper into this pathological process, the study employed bioinformatics to identify and analyze genes highly active in DPN. The investigation revealed that Membrane metallo-endopeptidase (MME) was effectively mitigated by its antagonist. Male Sprague-Dawley (SD) rats served as the model to systematically explore the intrinsic connection among the nociceptible/orphanin FQ-N/OFQ receptor (N/OFQ-NOP) system, femoral artery blood flow in the lower extremities, MME, and DPN. The rats were randomized into two groups: a control group and a DPN group induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ), with 6 rats in each group. The findings indicated that compared to the control group, the DPN group exhibited a significant reduction in femoral artery blood flow. This was accompanied by a notable increase in serum N/OFQ concentration, heightened expression of opioid-related nociceptive protein receptor 1 (OPRL1) and MME in femoral artery tissues of the lower limbs, and an elevated sciatic nerve stimulation threshold. These results suggest that the serum N/OFQ level in DPN rats is increased, which may promote the occurrence of peripheral neuropathy by up regulating MME and reducing peripheral flow distribution.

糖尿病周围神经病变（DPN）是糖尿病的常见并发症，常伴有下肢血管内皮功能受损。这种功能障碍的特点是血管舒张反应降低，导致下肢血流量减少，最终导致糖尿病周围神经病变的发展。为了深入研究这一病理过程，本研究采用生物信息学方法对DPN中高活性的基因进行了鉴定和分析。研究发现，膜金属内肽酶（MME）拮抗剂能有效减轻其活性。以雄性SD大鼠为研究对象，系统探讨了痛觉/孤儿蛋白FQ-N/OFQ受体（N/OFQ- nop）系统、下肢股动脉血流、MME和DPN之间的内在联系。随机分为对照组和单次腹腔注射链脲佐菌素（STZ） 55 mg/kg诱导DPN组，每组6只。研究结果表明，与对照组相比，DPN组的股动脉血流明显减少。与此同时，血清N/OFQ浓度显著升高，下肢股动脉组织中阿片相关伤害性蛋白受体1 （OPRL1）和MME表达升高，坐骨神经刺激阈值升高。上述结果提示，DPN大鼠血清N/OFQ水平升高，可能通过上调MME，降低外周血流分布，促进周围神经病变的发生。

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引用次数: 0

FMRFamide G protein-coupled receptors (GPCR) in the cuttlefish Sepiella japonica: Identification, characterization and expression profile 墨鱼FMRFamide G蛋白偶联受体（GPCR）的鉴定、表征和表达谱。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-01-01 DOI: 10.1016/j.npep.2024.102491

Jian-jun Xie , Ying Li , Jun-hong Wu, Pei-xuan Fang, Shuang Li, Xu Zhou, Chang-feng Chi

FMRFamide is a ubiquitous neuromodulator in the animal kingdom. Once FMRFamide or similar neuropeptides bind to their G protein-coupled receptors (GPCR), a series of signal transduction events are triggered, thereby mediating various physiological effects. FMRFamide had been reported to be involved in the regulation of sexual maturation in Sepiella japonica. In this research, the full-length cDNA of FMRFamide G protein-coupled receptor of S. japonica (SjFaGPCR) was cloned. The sequence is 1396 bp long and encodes a protein consisting of 418 amino acid residues, lacking a signal peptide at the N-terminal region. The 3D structure of SjFaGPCR was predicted using Todarodes pacificus rhodopsin as a template, and the result indicated the presence of seven transmembrane regions. Multiple sequence alignments and phylogenetic trees indicated that SjFaGPCR is conserved among invertebrates, and shares highly similar sequence characteristics with other cephalopods. In situ hybridization (ISH) results revealed that significant signals of SjFaGPCR were detected in the central medulla and the granular layer cells of the optic lobe, and were also observed in the supraesophageal and subesophageal masses of the brain. Meanwhile, quantitative real-time PCR (qRT-PCR) results showed that a higher expression level of SjFaGPCR mRNA was detected in the brain and optic lobe of female cuttlefish at stage III and stage VI, and also in the brain (stage V) and optic lobe (stages IV and V) of male cuttlefish than that in other tissues. The co-localization results demonstrated that fluorescence signals of SjFMRFamide and SjFaGPCR were overlapped in HEK293 cells, suggesting a possible interaction between the SjFMRFamide and SjFaGPCR. These findings provide molecular support for further exploring the roles of FMRFamide and FaGPCR in the reproductive regulation of S. japonica.

FMRFamide是动物王国中普遍存在的神经调节剂。一旦FMRFamide或类似的神经肽与其G蛋白偶联受体（GPCR）结合，就会触发一系列信号转导事件，从而介导各种生理效应。据报道，FMRFamide参与了Sepiella japonica的性成熟调节。本研究克隆了粳稻FMRFamide G蛋白偶联受体的全长cDNA （SjFaGPCR）。该序列长1396 bp，编码一个由418个氨基酸残基组成的蛋白，在n端缺失一个信号肽。以太平洋红紫质为模板预测SjFaGPCR的三维结构，结果表明存在7个跨膜区。多重序列比对和系统发育树分析表明，SjFaGPCR在无脊椎动物中具有保守性，与其他头足类动物具有高度相似的序列特征。原位杂交（ISH）结果显示，在中央髓质和视叶颗粒层细胞中检测到显著的SjFaGPCR信号，在脑食管上和食管下肿物中也观察到。同时，实时荧光定量PCR （qRT-PCR）结果显示，SjFaGPCR mRNA在III期和VI期雌性墨鱼的大脑和视叶，以及雄性墨鱼的大脑（V期）和视叶（IV期和V期）中的表达水平高于其他组织。共定位结果表明，SjFMRFamide和SjFaGPCR的荧光信号在HEK293细胞中存在重叠，提示SjFMRFamide和SjFaGPCR可能存在相互作用。这些发现为进一步探索FMRFamide和FaGPCR在粳稻生殖调控中的作用提供了分子支持。

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引用次数: 0

Antioxidant PRDX3 gene therapy protects brain cells and prevents neurodegeneration in an animal model of Parkinson's disease 抗氧化剂 PRDX3 基因疗法在帕金森病动物模型中保护脑细胞并防止神经变性。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-12-27 DOI: 10.1016/j.npep.2024.102494

Sheila Adela Villa-Cedillo , Esrom Jared Acosta-Espinoza , Adolfo Soto-Domínguez , Humberto Rodríguez-Rocha , Carlos R. Montes-de-Oca-Saucedo , Aracely García-García , María de Jesús Loera-Arias , Cristina Sarahi Ríos-Vazquez , Guillermo Sánchez-Torres , Jesús Valdés , Odila Saucedo-Cárdenas

Neurodegenerative diseases, including Parkinson's Disease (PD), are a significant global health challenge with no effective therapies to counteract neurodegeneration. Genetic and environmental factors lead to mitochondrial dysfunction and increased reactive oxygen species (ROS), resulting in oxidative stress. This stress reduces levels of Peroxiredoxin 3 (PRDX3), a key protein for maintaining ROS balance at the mitochondrial level, increasing the substantia nigra's susceptibility to damage. To investigate the protective role of antioxidant gene therapy in a PD model, we overexpressed the PRDX3 enzyme using a cell-penetrating peptide-based delivery system (mRVG9R-PRDX3 complex). The mRVG9R peptide was combined with a green fluorescent protein (GFP) reporter plasmid expressing PRDX3 to create the complex. Overexpression of the PRDX3 gene in neuronal phenotype cells was confirmed in vitro using dopaminergic SH-SY5Y cells. Following successful in vitro expression, the mRVG9R-PRDX3 complex was stereotaxically injected into the striatum of male C57BL/6 mice. The PD model was induced by administering paraquat (PQ) twice a week for 6 weeks. After the final PQ injection, motor and cognitive functions were evaluated, followed by histological analysis. Animals treated with the mRVG9R-PRDX3 complex showed a clear reduction in PQ-induced PD symptomatology and prevented cellular senescence in the substantia nigra's neuronal population. The mRVG9R-PRDX3 gene therapy improved motor and cognitive functions in the PD animal model and demonstrated potential in protecting substantia nigra dopaminergic neurons from PQ-induced death.

神经退行性疾病，包括帕金森病（PD），是一个重大的全球健康挑战，没有有效的治疗方法来对抗神经退行性疾病。遗传和环境因素导致线粒体功能障碍和活性氧（ROS）增加，导致氧化应激。这种应激降低了过氧化物还氧蛋白3 （PRDX3）的水平，PRDX3是维持线粒体水平活性氧平衡的关键蛋白，增加了黑质对损伤的易感性。为了研究抗氧化基因治疗在帕金森病模型中的保护作用，我们使用基于细胞穿透肽的递送系统（mRVG9R-PRDX3复合物）过表达PRDX3酶。mRVG9R肽与表达PRDX3的绿色荧光蛋白（GFP）报告质粒结合，形成复合物。体外多巴胺能SH-SY5Y细胞证实了PRDX3基因在神经元表型细胞中的过表达。体外表达成功后，将mRVG9R-PRDX3复合物立体定向注射到雄性C57BL/6小鼠纹状体中。采用百草枯（PQ）灌胃，每周2次，连续灌胃6周。最后一次注射PQ后，评估运动和认知功能，然后进行组织学分析。用mRVG9R-PRDX3复合物治疗的动物显示pq诱导的PD症状明显减少，并阻止了黑质神经元群的细胞衰老。mRVG9R-PRDX3基因治疗可改善帕金森病动物模型的运动和认知功能，并显示出保护黑质多巴胺能神经元免受pq诱导死亡的潜力。

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引用次数: 0

Phoenixin-14 inhibits the formation of cerebral aneurysms in rats by downregulating the p38/NF-κB signaling pathway 凤凰素14通过下调p38/NF-κB信号通路抑制大鼠脑动脉瘤的形成。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-12-20 DOI: 10.1016/j.npep.2024.102493

Qizheng Li , Lin Zeng , Songyang Peng , Mengting Zhu , Yaodan Zhang

Cerebral aneurysms (CA) are a serious condition characterized by the bulging of a blood vessel in the brain, which can lead to rupture and life-threatening bleeding. The pathophysiology of CA involves complex processes, particularly inflammation and macrophage infiltration. Phoenixin-14 (PNX-14) is a neuropeptide with diverse biological effects, including roles in reproduction, energy homeostasis, and inflammation. Recent evidence has highlighted the therapeutic potential of PNX-14 in various conditions. Notably, PNX-14 has demonstrated neuroprotective effects in the central nervous system, and we hypothesized that it could also offer vascular protection in the context of CA. In this study, we demonstrate that serum PNX-14 levels are reduced in patients and rat models with CA compared to healthy controls. Our findings show that PNX-14 administration significantly reduces aneurysmal size in a rat model with left renal artery ligation. Furthermore, PNX-14 mitigates the inflammatory response by inhibiting the expression of IL-1β and MCP-1 at both the mRNA and protein levels in the Circle of Willis (COW) region. PNX-14 treatment also decreases the levels of MMP-2 and MMP-9 in the COW region. Mechanistically, PNX-14 suppresses macrophage infiltration and inhibits the activation of the p38/NF-κB signaling pathway. These findings suggest that PNX-14 could be a promising therapeutic agent for the prevention and treatment of CA.

脑动脉瘤（CA）是一种严重的疾病，其特征是大脑血管膨胀，可能导致破裂和危及生命的出血。CA的病理生理过程复杂，尤其是炎症和巨噬细胞浸润。Phoenixin-14 （PNX-14）是一种具有多种生物学作用的神经肽，包括生殖、能量稳态和炎症。最近的证据强调了PNX-14在各种情况下的治疗潜力。值得注意的是，PNX-14在中枢神经系统中显示出神经保护作用，我们假设它也可以在CA的情况下提供血管保护。在本研究中，我们证明与健康对照组相比，CA患者和大鼠模型的血清PNX-14水平降低。我们的研究结果表明，PNX-14给药可显著减少左肾动脉结扎大鼠模型的动脉瘤大小。此外，PNX-14通过抑制威利斯圈（COW）区mRNA和蛋白水平上IL-1β和MCP-1的表达来减轻炎症反应。PNX-14处理也降低了奶牛区MMP-2和MMP-9的水平。机制上，PNX-14抑制巨噬细胞浸润，抑制p38/NF-κB信号通路的激活。这些结果提示PNX-14可能是一种很有前景的预防和治疗CA的药物。

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引用次数: 0

Protective effect of Apelin-13 on D-glutamic acid-induced excitotoxicity in SH-SY5Y cell line: An in-vitro study Apelin-13对D-谷氨酸诱导的SH-SY5Y细胞系兴奋毒性的保护作用：体外研究

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-11-12 DOI: 10.1016/j.npep.2024.102483

Kadriye Yağmur Oruç , Gökhan Ağtürk , Aykut Oruç , Karolin Yanar , Hakkı Oktay Seymen

Excitotoxicity, resulting from excessive accumulation of glutamate in the extracellular space, leads to neuronal cell death. This study investigates the protective effects of Apelin-13 on D-Glutamic acid-induced excitotoxicity in SH-SY5Y human neuroblastoma cells, an in-vitro model for neurodegenerative diseases. Unlike the commonly studied L-glutamic acid, this research focuses on D-Glutamic acid to understand its specific impacts. SH-SY5Y cells were treated with varying concentrations of D-Glutamic acid and Apelin-13, followed by analyses at 12 and 24 h to evaluate cell viability, oxidative stress markers, and inflammatory cytokine levels. Cell viability assays revealed significant cytotoxic effects of D-Glutamic acid at doses of 10 mM and 20 mM, reducing viability by over 50 %. However, Apelin-13 treatment mitigated these effects, especially at 2 μg/ml, enhancing cell viability and reducing inflammatory cytokine levels (IL-1β and TNF-α). Apelin-13 also increased anti-inflammatory cytokine levels (IL-10 and TGF-β1) and brain-derived neurotrophic factor (BDNF), indicating its neuroprotective role. Oxidative stress markers, including ROS, AGE, AOPP, DT, T-SH, were significantly elevated by D-Glutamic acid but effectively reduced by Apelin-13. The neuroprotective mechanisms of Apelin-13 involve modulation of cAMP/PKA and MAPK signaling pathways, enhancing BDNF synthesis and suppressing oxidative stress and inflammatory responses. This study is the first to demonstrate the effects of D-Glutamic acid on SH-SY5Y cells. It highlights Apelin-13's potential as a therapeutic agent against excitotoxicity-induced neuronal damage, emphasizing its ability to modulate key molecular pathways involved in inflammation and oxidative stress. Further in-vivo studies are warranted to explore the long-term neuroprotective effects of Apelin-13 in treating neurodegenerative diseases.

谷氨酸在细胞外空间的过度积累会导致兴奋性中毒，从而导致神经细胞死亡。本研究调查了 Apelin-13 对 D-谷氨酸诱导的 SH-SY5Y 人类神经母细胞瘤细胞兴奋毒性的保护作用，SH-SY5Y 人类神经母细胞瘤细胞是神经退行性疾病的体外模型。与通常研究的 L-谷氨酸不同，本研究侧重于 D-谷氨酸，以了解其具体影响。用不同浓度的 D-谷氨酸和 Apelin-13 处理 SH-SY5Y 细胞，然后在 12 和 24 小时后进行分析，以评估细胞活力、氧化应激标记物和炎症细胞因子水平。细胞活力测定显示，剂量为 10 毫摩尔和 20 毫摩尔的 D-谷氨酸具有明显的细胞毒性作用，可使细胞活力降低 50%以上。然而，Apelin-13 处理可减轻这些影响，尤其是在 2 μg/ml 剂量时，可提高细胞活力并降低炎性细胞因子水平（IL-1β 和 TNF-α）。Apelin-13还能提高抗炎细胞因子（IL-10和TGF-β1）和脑源性神经营养因子（BDNF）的水平，表明其具有神经保护作用。氧化应激标志物，包括 ROS、AGE、AOPP、DT、T-SH，在 D-谷氨酸的作用下显著升高，但 Apelin-13 能有效降低这些标志物。Apelin-13的神经保护机制包括调节cAMP/PKA和MAPK信号通路，促进BDNF合成，抑制氧化应激和炎症反应。这项研究首次证明了 D-谷氨酸对 SH-SY5Y 细胞的影响。该研究强调了 Apelin-13 作为一种治疗剂来对抗兴奋性毒性诱导的神经元损伤的潜力，并强调了其调节参与炎症和氧化应激的关键分子通路的能力。有必要进一步开展体内研究，探索 Apelin-13 在治疗神经退行性疾病方面的长期神经保护作用。

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引用次数: 0

Neuroanatomical mapping of spexin and nesfatin-1-expressing neurons in the human brainstem 人类脑干中表达 spexin 和 nesfatin-1 神经元的神经解剖图。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-11-08 DOI: 10.1016/j.npep.2024.102484

Artur Pałasz , Klaudia Ozimirska , Aleksandra Suszka-Świtek , Katarzyna Bogus , Iwona Błaszczyk , Veerta Sharma , Marta Pukowiec , John J. Worthington , Izabela Młynarczuk-Biały , Anna Lipiec-Borowicz

Neuropeptides are involved in numerous brain activities being able to control a wide spectrum of physiological functions. In recent years, a number of novel pleiotropic regulatory peptides have been discovered in animal brain structures. The purpose of this descriptive neurochemical investigation was to detect the possible expression of the novel multifunctional neuropeptides spexin (SPX) and nesfatin-1 within the human brainstem. Using immunohistochemical and fluorescence techniques, neuroanatomical analysis of the SPX and nesfatin-1 expression and distribution was performed in selected sections of the human midbrain and medulla oblongata. The presence of SPX-positive neurons in the human brainstem was revealed for the first time and previous reports on the expression of nesfatin-1 were additionally confirmed. The research results suggest that SPX and nesfatin-1 are new regulatory neuropeptides of the human brainstem potentially involved in the regulation of key autonomic activities of this brain region.

神经肽参与多种大脑活动，能够控制多种生理功能。近年来，在动物大脑结构中发现了一些新型的多效调节肽。这项描述性神经化学研究的目的是检测新型多功能神经肽spexin（SPX）和nesfatin-1在人类脑干中的可能表达。研究人员利用免疫组化和荧光技术，在人中脑和延髓的部分切片中对 SPX 和 nesfatin-1 的表达和分布进行了神经解剖学分析。研究首次发现人脑干中存在 SPX 阳性神经元，并进一步证实了之前关于内司蛋白-1 表达的报道。研究结果表明，SPX 和 nesfatin-1 是人类脑干新的调节神经肽，可能参与调节该脑区的主要自律神经活动。

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引用次数: 0

Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice 神经肽 FF 通过非 NPFF 受体机制防止雄性小鼠出现组胺或氯喹诱发的急性瘙痒行为

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-11-04 DOI: 10.1016/j.npep.2024.102481

Honghai Tang , Ting Zhang , Jiamin Feng , Mengna Zhang , Biao Xu , Qinqin Zhang , Ning Li , Nan Zhang , Quan Fang

The neuropeptide FF (NPFF) system regulates various physiological and pharmacological functions, particularly pain modulation. However, the modulatory effect of NPFF system on itch remains unclear. To investigate the modulatory effect and functional mechanism induced by NPFF system on acute itch, we examined the effects of supraspinal administration of NPFF and related peptides on acute itch induced by intradermal (i.d.) injection of histamine or chloroquine in male mice. Our results indicated that intracerebroventricular (i.c.v.) administration of NPFF dose-dependently prevented histamine- or chloroquine-induced acute itch behaviors. In addition, the modulatory effect of NPFF was not affected by the selective NPFF receptor antagonist RF9. Furthermore, we investigated the effects of NPVF and dNPA, the selective agonists of NPFF₁ and NPFF₂ receptors respectively, on the acute itch. The results demonstrated that both NPFF agonists effectively prevented acute itch induced by histamine or chloroquine in a manner similar to NPFF, and their effects were also not modified by RF9. To further investigate the possible mechanism of the NPFF receptors agonists, the NPFF-derived analogues [Phg⁸]-NPFF and NPFF(1–7)-NH₂ that could not activate NPFF receptors in cAMP assays were subsequently tested in the acute itch model. Interestingly, [Phg⁸]-NPFF, but not NPFF(1–7)-NH₂, prevented acute itch behavior after i.c.v. administration. In conclusion, our findings reveal that NPFF and related peptides prevent histamine- and chloroquine-induced acute itch through a NPFF receptor-independent mechanism. And it was revealed that the C-terminal phenyl structure of NPFF may play a crucial role in these modulatory effects on acute itch.

神经肽 FF（NPFF）系统调节各种生理和药理功能，尤其是疼痛调节功能。然而，NPFF系统对痒的调节作用仍不清楚。为了研究 NPFF 系统对急性瘙痒的调节作用和功能机制，我们研究了在雄性小鼠皮内注射组胺或氯喹引起的急性瘙痒时，椎上注射 NPFF 和相关肽的影响。我们的研究结果表明，脑室内注射 NPFF 可剂量依赖性地阻止组胺或氯喹诱发的急性瘙痒行为。此外，NPFF的调节作用不受选择性NPFF受体拮抗剂RF9的影响。此外，我们还研究了 NPVF 和 dNPA（分别是 NPFF1 和 NPFF2 受体的选择性激动剂）对急性瘙痒的影响。结果表明，这两种NPFF受体激动剂都能有效地防止组胺或氯喹诱导的急性瘙痒，其作用方式与NPFF相似，而且RF9也不会改变它们的作用。为了进一步研究 NPFF 受体激动剂的可能机制，随后在急性瘙痒模型中测试了在 cAMP 试验中不能激活 NPFF 受体的 NPFF 衍生类似物 [Phg8]-NPFF 和 NPFF（1-7）-NH2。有趣的是，[Phg8]-NPFF（而非 NPFF（1-7）-NH2）在静脉注射后能防止急性瘙痒行为。总之，我们的研究结果表明，NPFF 和相关肽通过一种与 NPFF 受体无关的机制防止组胺和氯喹引起的急性瘙痒。研究还发现，NPFF 的 C 端苯基结构可能在这些对急性瘙痒的调节作用中发挥了关键作用。

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引用次数: 0

Neuropeptides or their receptors in pathogenesis of lung diseases and therapeutic potentials 肺部疾病发病机制中的神经肽或其受体及其治疗潜力。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-11-02 DOI: 10.1016/j.npep.2024.102482

Changgen Li , Na Zang , Enmei Liu

There are complex interactions between the immune system and the nervous system in the lung. The nervous system perceives environmental stimuli and transmits these signals to immune cells via neurotransmitters, which is essential for effective immunity and environmental balance. Neuropeptides are important neurotransmitters in the lung, where they regulate immune responses through direct and indirect mechanisms, affecting the occurrence and development of lung diseases. In this review, we emphasize the role of neuropeptides in the pathogeneis of lung diseases and their potential therapeutic value for lung diseases.

肺部的免疫系统和神经系统之间存在着复杂的相互作用。神经系统感知环境刺激，并通过神经递质将这些信号传递给免疫细胞，这对有效免疫和环境平衡至关重要。神经肽是肺部重要的神经递质，通过直接和间接机制调节免疫反应，影响肺部疾病的发生和发展。在这篇综述中，我们强调了神经肽在肺部疾病病因中的作用及其对肺部疾病的潜在治疗价值。

引用次数: 0

Neuritogenesis and protective effects activated by Angiotensin 1–7 in astrocytes-neuron interaction 血管紧张素 1-7 在星形胶质细胞与神经元相互作用中激活的神经细胞生成和保护作用

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-10-28 DOI: 10.1016/j.npep.2024.102480

Gabriel Alberto de Carvalho Barbosa , Marina Prado Rubinho , Milton Kennedy Aquino-Júnior , Jéssica Rodrigues Pedro , Lívia Fligioli Donato , Leonardo Trisciuzzi , Alessandra Oliveira Silva , Silvia Graciela Ruginsk , Carla Speroni Ceron , Nathalia Peixoto , Marcos Vinícios Salles Dias , Marília Gabriella Alves Goulart Pereira

The renin angiotensin system (RAS) has been studied for its effects on various neurological disorders. The identification of functional receptors for Ang-(1–7) and Ang II peptides in astrocytes highlights the physiological modulation and the important role of these cells in the central nervous system. The present study aims to understand the role of RAS peptides, particularly Ang-(1–7) and Ang II, in the secretion of trophic factors by astrocytes and their effects on hippocampal neurons. We used primary cultures of astrocytes and neurons from the hippocampus of either sex neonate of Wistar strain rats. In the present study, we demonstrated that the treatment of astrocytes with Ang-(1–7) acts on the modulation of these cells, inducing reactive astrogliosis, identified through the increase in the expression of GFAP. Furthermore, we obtained a conditioned medium from astrocytes treated with Ang-(1–7), which in addition to promoting the secretion of neurotrophic factors essential for neuronal-glial interactions that are fundamental for neuritogenesis and neuronal survival, showed a neuroprotective effect against glutamatergic excitotoxicity. In turn, Ang II does not exhibit the same effects on astrocyte modulation, exacerbating deleterious effects on brain RAS. Neuron-astrocyte interactions have been shown to be an integral part of the central effects mediated by RAS, and this study has significantly contributed to the understanding of the biochemical mechanisms involved in the functioning of this system.

人们一直在研究肾素血管紧张素系统（RAS）对各种神经系统疾病的影响。在星形胶质细胞中发现了 Ang-(1-7) 和 Ang II 肽的功能受体，突显了这些细胞在中枢神经系统中的生理调节和重要作用。本研究旨在了解 RAS 肽（尤其是 Ang-(1-7) 和 Ang II）在星形胶质细胞分泌营养因子中的作用及其对海马神经元的影响。我们使用了来自 Wistar 株大鼠海马的星形胶质细胞和神经元原代培养物。在本研究中，我们证明了 Ang-(1-7) 对星形胶质细胞的作用，即通过增加 GFAP 的表达诱导反应性星形胶质细胞增生。此外，我们还从用 Ang-(1-7) 处理过的星形胶质细胞中获得了一种条件培养基，这种培养基除了能促进神经元-胶质细胞相互作用所必需的神经营养因子（神经元-胶质细胞相互作用是神经元发生和存活的基础）的分泌外，还对谷氨酸能兴奋毒性具有神经保护作用。反过来，Ang II 对星形胶质细胞的调节作用却不尽相同，从而加剧了对大脑 RAS 的有害影响。神经元与星形胶质细胞之间的相互作用已被证明是 RAS 所介导的中枢效应的一个组成部分，这项研究极大地促进了人们对这一系统运作所涉及的生化机制的理解。

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