Neuropeptides最新文献

The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN) 促肾上腺皮质激素释放因子（CRF）和尿皮质素对中脑核（RN）释放血清素（羟色胺，5HT）的影响。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-01-09 DOI: 10.1016/j.npep.2025.102503

Aliz Kovács , Patrícia Tancsics , Miklós Palotai , Zsolt Bagosi

Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides. They regulate the neuroendocrine, autonomic and behavioral responses to stress via two CRF receptors (CRF1 and CRF2). Stress, anxiety and depression affects the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the serotoninergic neurotransmission, both being regulated by CRF and CRF-related peptides. However, the exact action of CRF and urocortins on the serotonin (5-hydroxytryptamine, 5HT) release was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the 5HT released from the rat raphe nuclei (RN), the most important brain regions producing 5HT, and the participation of CRF receptors in these actions. In order to do so, male Wistar rats were used, their RN were isolated and dissected, and the RN slices were incubated with tritium-labelled 5HT, superfused and stimulated electrically. During superfusion, the RN slices were treated with CRF, UCN1, UCN2 or UCN3, and, when significant effect was observed, pretreated with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B. The release of tritium-labelled 5HT from the RN was determined by liquid scintillation counting. CRF and UCN1 decreased significantly the tritium-labelled 5HT release from the RN, and these effects were reversed by antalarmin, but not by astressin2B. In addition, UCN3, but not UCN2, increased significantly the tritium-labelled 5HT release from the RN, and this effect was reduced by astressin2B, but not antalarmin. Our results indicate the existence of two apparently opposing CRF systems in the RN: activation of CRF1 by CRF and UCN1 may inhibit, whereas activation of CRF2 by UCN3 may stimulate the 5HT release. The dysbalance between CRF1 and CRF2 activation and, consequently, alteration of serotoninergic signalling may result in anxiety and depression, associated with hyperactivity of the HPA axis.

促肾上腺皮质激素释放因子（CRF）和尿皮质素（UCN1、UCN2和UCN3）属于同一个CRF神经肽家族。它们通过两个CRF受体（CRF1和CRF2）调节神经内分泌、自主神经和对压力的行为反应。应激、焦虑和抑郁影响下丘脑-垂体-肾上腺（HPA）轴的活动和血清素能神经传递，两者都受CRF和CRF相关肽的调节。然而，CRF和尿皮质素对血清素（5-羟色胺，5HT）释放的确切作用尚未完全阐明。因此，本研究的目的是研究CRF和尿皮质素对大鼠中隔核（RN）释放5HT的作用，以及CRF受体在这些作用中的参与。中隔核是产生5HT的最重要的脑区。为此，使用雄性Wistar大鼠，分离并解剖其RN，将RN切片与氚标记的5HT孵育，并进行超灌注和电刺激。在灌注过程中，分别用CRF、UCN1、UCN2或UCN3处理RN切片，当观察到有显著效果时，再用选择性CRF1拮抗剂安talarmin或选择性CRF2拮抗剂astressin2B预处理。通过液体闪烁计数测定氚标记的5HT从RN的释放量。CRF和UCN1显著降低了RN中氚标记的5HT的释放，这些作用被安塔拉明逆转，但不被应激素2b逆转。此外，UCN3显著增加了RN中氚标记的5HT的释放，而UCN2则没有，并且这种作用被astressin2B而不是antalarmin所降低。我们的研究结果表明，在RN中存在两种明显相反的CRF系统：CRF和UCN1激活CRF1可能会抑制，而UCN3激活CRF2可能会刺激5HT的释放。CRF1和CRF2激活之间的失衡以及由此引起的5 -羟色胺能信号的改变可能导致焦虑和抑郁，并与HPA轴的过度活跃有关。

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引用次数: 0

Sucralose uses reward pathways to promote acute caloric intake 三氯蔗糖利用奖励途径促进急性热量摄入。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-01-06 DOI: 10.1016/j.npep.2025.102502

Qiao-Ping Wang , An-Qi Li , Bei Wang , Xin-Yuan Zhao , Sha-Sha Li , Herbert Herzog , G. Gregory Neely

Non-nutritive sweeteners (NNSs) are used to reduce caloric intake by replacing sugar with compounds that are sweet but contain little or no calories. In this study, we investigate how non-nutritive sweetener sucralose to promote acute food intake in the fruit fly Drosophila melanogaster. Our results showed that acute exposure to NNSs sweetness induces a robust hyperphagic response in flies. Cellular and molecular dissection of this acute effect revealed the requirement of a reward pathway comprising of sweet taste neurons, octopaminergic neurons, and NPF neurons which drive increased food intake in response to sucralose. These data provide mechanistic insight into how NNSs can increase food intake, information that may help us better understand how artificially sweeteners may impact our physiology.

非营养性甜味剂（NNSs）是用来减少热量摄入的，它是用甜的但含有很少或不含热量的化合物来代替糖。在这项研究中，我们研究了非营养性甜味剂三氯蔗糖如何促进果蝇的急性食物摄入。我们的研究结果表明，急性暴露于NNSs甜度会引起果蝇强烈的贪食反应。对这种急性效应的细胞和分子解剖揭示了由甜味神经元、八胺能神经元和NPF神经元组成的奖赏通路的要求，这些神经元驱动对三氯蔗糖的食物摄入增加。这些数据为NNSs如何增加食物摄入量提供了机制上的见解，这些信息可能有助于我们更好地理解人工甜味剂如何影响我们的生理。

引用次数: 0

Transcranial pulsed current stimulation alleviates neuronal pyroptosis and neurological dysfunction following traumatic brain injury via the orexin-A/NLRP3 pathway

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.

{"title":"Transcranial pulsed current stimulation alleviates neuronal pyroptosis and neurological dysfunction following traumatic brain injury via the orexin-A/NLRP3 pathway","authors":"Peng Yao , Qianhui Zhou , Bingkai Ren , Li Yang , Yang Bai , Zhen Feng","doi":"10.1016/j.npep.2025.102501","DOIUrl":"10.1016/j.npep.2025.102501","url":null,"abstract":"<div><div>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 (OX<sub>1</sub>R) 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 OX<sub>1</sub>R/NLRP3 pathway to mitigate the inflammatory response following TBI, thereby exerting neuroprotective effects.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"110 ","pages":"Article 102501"},"PeriodicalIF":2.5,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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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