Neuropeptides最新文献_第5页

Profile of cocaine and amphetamine regulated transcript peptide (CARTp) and Corticotropin-releasing factor (CRF) in the brain of Euphlyctis cyanophlyctis during puddle desiccation 可卡因和安非他明在水坑干燥时调节蓝绿炎脑内转录肽（CARTp）和促肾上腺皮质激素释放因子（CRF）的特征。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-03-15 DOI: 10.1016/j.npep.2025.102518

Swapnil A. Shewale , Sunil J. Koli , Sneha Sagarkar , Ameeta Ravikumar , Shobha Bhargava

During the post breeding season, anuran tadpoles are subjected to a wide range of environmental variables due to intermittent dry spells leading to pond desiccation. To avoid these harsh conditions, anurans accelerate rate of metamorphosis. In anurans, hypothalamic corticotropin-releasing factor (CRF) senses stress and activates metamorphosis via hypothamalo-pituitary- interenal/thyroid axis. Cocaine and amphetamine regulated transcript peptide (CARTp) is widely reported in the brains of vertebrates except reptiles. Role of CARTp along with CRF in mitigating the physiological effects of stress in mammals is well established. Therefore, we investigated effect of puddle desiccation on the CARTp and CRF peptide immunoreactivity in the brain of prometamorphic tadpoles of Euphlyctis cyanophlyctis. Animals in the naturally occurring desiccating puddle were fixed on field and the expression of CARTp and CRF were studied using immunohistochemistry. CARTp-immunoreactivity in entopeduncular nucleus (AEN and PEN), nucleus medialis septi (NMS) and hypothalamus (dHy and vHy) significantly increased in the prometamorphic tadpoles exposed to puddle desiccation as compared to controls. In preoptic area (POA) and Edinger Westphal nucleus (EW) significant increase in CARTp as well as CRF immunoreactive cells were observed in puddle desiccation group. Strong CRF immunoreactivity was observed in median eminence of stressed group. Puddle desiccation induced increase in the expression of CARTp and CRF peptide in the neuroendocrine axis may suggest their involvement in environmental stress induced accelerated metamorphosis. Moreover, elevated expression of CARTp but not CRF peptide in regions regulating energy homeostasis may indicate starvation due to scarcity of food or stress induced appetite suppression.

在繁殖后的季节，由于间歇性干旱导致池塘干燥，无尾蝌蚪受到各种环境变量的影响。为了避免这些恶劣的环境，无脊椎动物加速了变态的速度。在无尾动物中，下丘脑促肾上腺皮质激素释放因子（CRF）通过下丘脑-垂体-内/甲状腺轴感知压力并激活变态。除爬行动物外，可卡因和安非他命调节转录肽（CARTp）广泛存在于脊椎动物的大脑中。CARTp和CRF在减轻哺乳动物应激生理效应中的作用已得到证实。因此，我们研究了水坑脱水对青绿幼稚蚪脑内CARTp和CRF肽免疫反应性的影响。将自然发生的干燥水坑中的动物固定在野外，用免疫组织化学方法研究CARTp和CRF的表达。与对照组相比，暴露于水坑脱水的早变质蝌蚪核内核（AEN和PEN）、中隔核（NMS）和下丘脑（dHy和vHy）的cartp免疫反应性显著升高。水坑干燥组视前区（POA）和Edinger Westphal核（EW）中CARTp和CRF免疫反应细胞显著升高。应激组正中隆起可见较强的CRF免疫反应性。水坑脱水导致神经内分泌轴上CARTp和CRF肽表达增加，可能与环境应激诱导的加速变态有关。此外，在调节能量稳态的区域，CARTp而非CRF肽的表达升高可能表明由于食物缺乏或应激引起的食欲抑制而导致饥饿。

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引用次数: 0

Factors affecting the physical stability of peptide self-assembly in neurodegenerative disorders 影响神经退行性疾病中多肽自组装物理稳定性的因素。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-03-13 DOI: 10.1016/j.npep.2025.102517

Jahnu Saikia , Mouli Sarkar , Vibin Ramakrishnan

Biological systems comprise of diverse biomolecules, including proteins, nucleic acids, lipids, and carbohydrates. Peptides, which are short chains of amino acids, exhibit unique properties when assembled to nano-level architectures. Self-assembling peptides possess a remarkable ability to organize into structured aggregates such as nanofibers, nanotubes, nanoribbons, and nanovesicles. These intricate structures are linked to neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Prion disease, Huntington's disease, and type II diabetes. Peptide nano assembly can be guided by external stimuli, such as temperature, pH, ultrasound, electric and magnetic fields. In this review, the discussion will be centred around the various factors that influence the self-assembly of peptides alongside therapeutic interventions that align with the fundamental principles of thermodynamics and kinetics to modulate the aggregation characteristics of peptide self-assembly.

生物系统由多种生物分子组成，包括蛋白质、核酸、脂质和碳水化合物。肽是一种短链氨基酸，在组装成纳米级结构时表现出独特的性质。自组装肽具有组织成结构聚集体的显著能力，如纳米纤维、纳米管、纳米带和纳米囊泡。这些复杂的结构与神经退行性疾病有关，包括阿尔茨海默病、帕金森氏病、朊病毒病、亨廷顿氏病和II型糖尿病。肽纳米组装可以受到外界刺激的引导，如温度、pH、超声、电场和磁场。在这篇综述中，讨论将集中在影响多肽自组装的各种因素，以及与热力学和动力学基本原理相一致的治疗干预措施，以调节多肽自组装的聚集特征。

引用次数: 0

Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders GDNF/GFRA1/RET和PI3K/AKT/ERK信号相互作用在神经保护中的分子机制：治疗神经系统疾病的治疗策略

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-03-12 DOI: 10.1016/j.npep.2025.102516

MD Nasiruddin Khan , Divya Choudhary , Sidharth Mehan , Zuber Khan , Ghanshyam Das Gupta , Acharan S. Narula

Neurological disorders, marked by progressive neuronal degeneration, impair essential cognitive functions like memory and motor coordination… This manuscript explores the significant roles of glial cell line-derived neurotrophic factor (GDNF), its co-receptors (GFRA1), and the receptor tyrosine kinase (RET) in mediating neuronal survival and function in various neurodegenerative conditions. The interplay between pivotal signaling pathways—PI3K/AKT and ERK1/2—facilitated by GDNF/GFRA1/RET, is emphasized for its neuroprotective effects. Dysregulation of these pathways is implicated in neurodegenerative and neuropsychiatric processes, with overactivation of GSK3β contributing to neuronal damage and apoptosis. Experimental evidence supports that activation of the RET receptor by GDNF enhances AKT signaling, promoting cell survival by inhibiting apoptotic pathways—therapeutic strategies incorporating GDNF delivery and RET activation present promising neuronal protection and regeneration options. Furthermore, inhibition of GSK3β demonstrates potential in ameliorating tau-related pathologies, while small molecule RET agonists may enhance therapeutic efficacy. This review explores the knowledge of GDNF/GFRA1/RET and PI3K/AKT/ERK1/2 associated signaling cascades, underscoring their significance in neuroprotection and therapeutic targeting to combat neurodegenerative diseases. Emerging approaches such as gene therapy and small-molecule RET agonists may offer novel avenues for treatment, although challenges like targeted delivery across the blood-brain barrier remain pertinent.

神经系统疾病，以进行性神经元变性为特征，损害了基本的认知功能，如记忆和运动协调…本文探讨了神经胶质细胞系来源的神经营养因子（GDNF），其共受体（GFRA1）和受体酪氨酸激酶（RET）在各种神经退行性疾病中介导神经元存活和功能的重要作用。GDNF/GFRA1/RET促进的关键信号通路pi3k /AKT和erk1 /2之间的相互作用强调了其神经保护作用。这些通路的失调与神经退行性和神经精神过程有关，GSK3β的过度激活有助于神经元损伤和凋亡。实验证据支持GDNF激活RET受体增强AKT信号，通过抑制凋亡途径促进细胞存活——结合GDNF和RET激活的治疗策略提供了有希望的神经元保护和再生选择。此外，抑制GSK3β显示出改善tau相关病理的潜力，而小分子RET激动剂可能增强治疗效果。本文综述了GDNF/GFRA1/RET和PI3K/AKT/ERK1/2相关信号级联的相关知识，强调了它们在神经保护和靶向治疗神经退行性疾病中的重要意义。诸如基因疗法和小分子RET激动剂等新兴方法可能为治疗提供新的途径，尽管诸如通过血脑屏障靶向递送等挑战仍然相关。

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引用次数: 0

Bioactive peptides as multipotent molecules bespoke and designed for Alzheimer's disease 生物活性肽是为阿尔茨海默病定制和设计的多能分子

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-03-04 DOI: 10.1016/j.npep.2025.102515

Ana Mesias, Sandra Borges, Manuela Pintado, Sara Baptista-Silva

In an increasingly aging world where neurodegenerative diseases (NDs) are exponentially rising, research into more effective and innovative treatments seems paramount. Bioactive peptides (BPs) emerge as promising compounds with revolutionary potential in the treatment of NDs, particularly in well-known conditions like Alzheimer's disease (AD). The biological potential of these compounds is primarily attributed to their drug development advantages such as enhanced penetration, low toxicity, and rapid clearance, as well as, their antioxidant, and anti-inflammatory properties bio-linked to the neuroprotective effect, able to attenuate the multifactorial pathologies of AD. BPs can be sourced from common dietary origins, like animals, plants, marine, and from emerging sources like edible insects. However, to isolate an active BP with beneficial biological effects it must first be released from its parent protein, followed by a synthesis-flow. While in silico approaches can predict a BP's potential bioactivity and structural characteristics, in vitro, cell-based, and in vivo assays should be conducted to ensure these properties. The blood-brain-barrier (BBB) microenvironment and permeability in health or disease state are key factors to consider since they can limit the ability of circulating therapeutical agents, including BPs, to reach the brain. This review focuses on the bioactivity properties of BPs from different dietary protein sources and explores their beneficial effect and neuroprotective activity in AD, unraveling new paths of treatment.

在一个日益老龄化的世界中，神经退行性疾病（NDs）呈指数级上升，研究更有效和创新的治疗方法似乎至关重要。生物活性肽（bp）作为一种具有革命性潜力的有前途的化合物出现在NDs的治疗中，特别是在阿尔茨海默病（AD）等众所周知的疾病中。这些化合物的生物学潜力主要归因于它们的药物开发优势，如增强渗透、低毒性和快速清除，以及它们的抗氧化和抗炎特性与神经保护作用生物相关，能够减轻AD的多因素病理。bp可以来自常见的饮食来源，如动物、植物、海洋，也可以来自可食用昆虫等新兴来源。然而，要分离出具有有益生物效应的活性BP，必须首先将其从母体蛋白中释放出来，然后进行合成流程。虽然计算机方法可以预测BP的潜在生物活性和结构特征，但应该进行体外、细胞和体内试验以确保这些特性。血脑屏障（BBB）微环境和健康或疾病状态下的渗透性是需要考虑的关键因素，因为它们可以限制循环治疗药物（包括bp）到达大脑的能力。本文综述了不同膳食蛋白质来源的bp的生物活性特性，并探讨了它们在AD中的有益作用和神经保护作用，揭示了新的治疗途径。

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引用次数: 0

Ginsenoside Rg1 improves autophagy dysfunction to ameliorate Alzheimer's disease via targeting FGR proto-oncogene 人参皂苷Rg1通过靶向FGR原癌基因改善自噬功能障碍，改善阿尔茨海默病

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-03-04 DOI: 10.1016/j.npep.2025.102514

Qiankun Quan , Xinxin Ma , JianJun Feng , Wanni Li , Xi Li

Alzheimer's disease (AD) is a neurodegeneration driven by beta-amyloid (Aβ) deposits in the brain involving autophagy dysfunction. Ginsenoside Rg1, a pharmacologically active compound found in ginseng, has possible therapeutic effects for AD. This study discovered that FGR proto-oncogene (FGR) was a therapeutic target of Rg1 in AD and it was possibly involved in autophagy. C57BL/6 J mice were injected with 5 μL (1 μg/mL) Aβ_1–42 in the right lateral ventricle to establish an AD model. AD mouse hippocampus had high FGR expression. Intragastrically administered Rg1 (40 mg/kg) decreased FGR protein levels in AD mice's hippocampus and improved memory function in AD mice. Both sides of the mice hippocampal fissure were administered with 2 μL lentiviral particles (1 × 10⁷ TU) containing FGR overexpression plasmids. FGR overexpression rendered Rg1 ineffectual in restoring memory function and reducing hippocampal neuron damage. We injected 2 μL lentiviral particles (1 × 10⁷ TU) containing short hairpin RNA plasmids targeting FGR to the mice hippocampal fissures. FGR knockdown improved spatial memory function of AD mice, reduced hippocampal neuron apoptosis, and prevented Aβ accumulation. HT22 cells were transfected with small interfering RNA targeting FGR. FGR knockdown increased the viability of Aβ_1–42 treated HT22 cells. BACE1 and LC3II/I protein levels were decreased and p62 and SIRT1 were increased in AD mice and cells with FGR knockdown. LC3 was down-regulated after inhibiting FGR expression in Aβ_1–42 treated hippocampal neurons. In conclusion, Rg1 exerts anti-AD functions by targeting FGR and downregulating its expression.

阿尔茨海默病（AD）是一种由大脑中β -淀粉样蛋白（a β）沉积引起的神经变性，涉及自噬功能障碍。人参皂苷Rg1是人参中发现的一种药理活性化合物，可能对阿尔茨海默病有治疗作用。本研究发现FGR原癌基因（FGR）是Rg1在AD中的治疗靶点，并可能参与自噬。将5 μL (1 μg/mL) Aβ1-42注入C57BL/6 J小鼠右侧脑室，建立AD模型。AD小鼠海马FGR高表达。灌胃Rg1 （40 mg/kg）可降低AD小鼠海马FGR蛋白水平，改善AD小鼠记忆功能。用含FGR过表达质粒的慢病毒颗粒2 μL （1 × 107 TU）灌胃小鼠海马双侧裂。FGR过表达使Rg1在恢复记忆功能和减轻海马神经元损伤方面无效。将含有短发夹RNA质粒的慢病毒颗粒（1 × 107 TU） 2 μL注射到小鼠海马裂隙中。FGR敲低可改善AD小鼠空间记忆功能，减少海马神经元凋亡，抑制Aβ积累。用靶向FGR的小干扰RNA转染HT22细胞。FGR敲除增加了Aβ1-42处理的HT22细胞的活力。在AD小鼠和FGR敲低的细胞中，BACE1和LC3II/I蛋白水平降低，p62和SIRT1升高。抑制Aβ1-42处理海马神经元FGR表达后，LC3下调。综上所述，Rg1通过靶向FGR并下调其表达来发挥抗ad功能。

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引用次数: 0

BDNF-mediated depressor response by direct baroreceptor activation benefits for prevention and control of hypertension in high-latitude cold region 通过直接激活气压感受器，BDNF 介导的降压反应有利于预防和控制高纬度寒冷地区的高血压

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-02-25 DOI: 10.1016/j.npep.2025.102506

Yan Feng , Lei Yin , Ying Li

Brian-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling impacts on neuronal and cardiovascular physiology; however, its role in neurocontrol of circulation via baroreflex afferent pathway is largely unknown. Gene and protein expression of BDNF/TrkB were detected in the nodose (NG) and nucleus of tractus solitary (NTS) and expression levels were higher in male compared with female rats, which is relevant well with the blood pressure (BP, males > females in average). Microinjection of BDNF into NG dose-dependently reduced BP and this reduction was more dramatic in shamed control vs. renovascular hypertension (RVH) model rats, which partially inhibited in the presence of TrkB inhibitor K252a, indicating that BDNF-TrkB tends to lower BP under physiological and hypertensive conditions due presumably to a negative feed-back control by BP or compensatory mechanism. To answer this question, expression profiles for BDNF-TrkB were tested in the tissue of NG and NTS collected from RVH model rats. Consistently, the expression of both BDNF-TrkB were significantly up-regulated in RVH model alone with the elevation of BP. Taken these data together, our observation provides direct evidence showing the fundamental role of BDNF-TrkB signaling in autonomic control of BP regulation through baroreflex afferent function, potentially dominant role of BDNF-TrkB-mediated BP reduction in vivo baroreceptor activation due to distinct cellular mechanism compared with their role in the NTS, which extends our understanding of activity-dependent or compensatory mechanism of BDNF-TrkB in response to BP change, and sheds new light of BDNF-TrkB as potential target in prevention and control of hypertension in cold-region.

脑源性神经营养因子(BDNF)-酪氨酸激酶B （TrkB）信号传导对神经元和心血管生理的影响然而，它在通过压力反射传入通路的循环神经控制中的作用在很大程度上是未知的。BDNF/TrkB基因和蛋白在结节（NG）和孤束核（NTS）中均有表达，且雄性大鼠表达量高于雌性大鼠，与血压(BP，雄性>；女性平均)。将BDNF微量注射到NG中，剂量依赖性地降低了血压，并且这种降低在羞愧对照与肾血管性高血压（RVH）模型大鼠中更为显著，RVH在TrkB抑制剂K252a的存在下部分抑制，表明BDNF-TrkB倾向于在生理和高血压条件下降低血压，可能是由于BP的负反馈控制或代偿机制。为了回答这个问题，我们在RVH模型大鼠的NG和NTS组织中检测了BDNF-TrkB的表达谱。与此一致的是，在RVH模型中，BDNF-TrkB的表达均随着血压升高而显著上调。综合这些数据，我们的观察结果提供了直接证据，表明BDNF-TrkB信号在通过压力反射传入功能自主控制血压调节中的基本作用，BDNF-TrkB介导的血压降低在体内压力感受器激活中的潜在主导作用，由于其不同的细胞机制，与它们在NTS中的作用相比，这扩展了我们对BDNF-TrkB响应血压变化的活性依赖或代偿机制的理解。揭示了BDNF-TrkB在寒冷地区高血压防控中的潜在靶点。

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引用次数: 0

Mechanistic role of proteins and peptides in Management of Neurodegenerative Disorders 蛋白质和多肽在神经退行性疾病治疗中的机制作用

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-02-13 DOI: 10.1016/j.npep.2025.102505

Saumya Awasthi , Prafulla Chandra Tiwari , Srishti Awasthi , Arpit Dwivedi , Shikha Srivastava

Proteins and peptides have emerged as significant contributors in the management of neurodegenerative disorders due to their diverse biological functions. These biomolecules influence various cellular processes, including cellular repair, inflammation reduction, and neuronal survival, which are crucial for mitigating the effects of diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS). By interacting with specific cellular receptors, proteins and peptides like neurotrophic factors, cytokines, and enzyme inhibitors promote neurogenesis, reduce oxidative stress, and enhance synaptic plasticity. Nevertheless, till certain limitations and challenges do exist to deliver these fragile therapeutic bioactives. Moreover, targeted delivery systems, such as nanoparticles and biomolecular carriers, are being developed to improve the bioavailability and specificity of these protein-based therapeutics, ensuring efficient crossing of the blood-brain barrier. This review explores the mechanistic pathways through which these biomolecules act, emphasizing their potential to modify disease progression and improve the quality of life in patients with neurodegenerative conditions. Overall, proteins and peptides are not only seen as promising therapeutic agents but also as foundational tools in advancing personalized medicine in the field of neurodegenerative disorders.

由于蛋白质和多肽具有不同的生物学功能，它们已成为神经退行性疾病治疗的重要贡献者。这些生物分子影响各种细胞过程，包括细胞修复、炎症减少和神经元存活，这对于减轻阿尔茨海默病、帕金森病和肌萎缩侧索硬化症（ALS）等疾病的影响至关重要。通过与特定的细胞受体、蛋白质和多肽如神经营养因子、细胞因子和酶抑制剂相互作用，促进神经发生，减少氧化应激，增强突触可塑性。然而，在提供这些脆弱的治疗性生物活性方面仍然存在某些限制和挑战。此外，正在开发靶向递送系统，如纳米颗粒和生物分子载体，以提高这些基于蛋白质的治疗方法的生物利用度和特异性，确保有效地穿过血脑屏障。这篇综述探讨了这些生物分子作用的机制途径，强调了它们在改变疾病进展和改善神经退行性疾病患者生活质量方面的潜力。总的来说，蛋白质和多肽不仅被视为有前途的治疗药物，而且是推进神经退行性疾病领域个性化医疗的基础工具。

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引用次数: 0

Modulation of temporoammonic-CA1 synapses by neuropeptide Y is through Y1 receptors in mice 神经肽Y通过Y1受体调节小鼠颞氨- ca1突触

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2025-02-03 DOI: 10.1016/j.npep.2025.102504

Mariana A. Cortes , Aundrea F. Bartley , Qin Li , Taylor R. Davis , Stephen E. Cunningham , Mary Anne Garner , Patric J. Perez , Adela C. Harvey , Alecia K. Gross , Lynn E. Dobrunz

Reduced levels of neuropeptide Y (NPY), an abundant neuromodulator in the brain, are linked to multiple neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is important for anxiety regulation and highly expresses NPY. Injecting NPY into CA1 is anxiolytic and alleviates behavioral symptoms in a model of traumatic stress; these anxiolytic effects are blocked by a Y1 receptor antagonist. However the location of Y1Rs that mediate NPY's anxiolytic effects in CA1 remains unclear. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which is important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this reduction is unknown. Here we demonstrate that in mice both exogenous (bath-applied) and endogenously-released NPY act through Y1 receptors in the TA pathway. This is the first demonstration of Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic overexpression of NPY (in NPY-expressing interneurons) impairs the sensitivity of the TA-evoked synaptic response to a Y1 receptor agonist. However, the long-known NPY Y2 receptor-mediated effect on the Schaffer collateral (SC) pathway is unaffected by NPY overexpression. Therefore, NPY can have a pathway-specific impact on synaptic transmission in CA1 based on the differential expression of NPY receptors and their response to overexpression of NPY. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.

神经肽Y （NPY）是大脑中丰富的神经调节剂，其水平降低与多种神经精神疾病有关，包括创伤后应激障碍（PTSD）。海马CA1区在焦虑调节中起重要作用，并高度表达NPY。在创伤应激模型中，向CA1注射NPY具有抗焦虑和缓解行为症状的作用；这些抗焦虑作用被Y1受体拮抗剂阻断。然而，介导NPY抗焦虑作用的Y1Rs在CA1中的位置尚不清楚。CA1通过颞氨通路（temporamic pathway， TA）接收来自内嗅皮层的输入，这一通路对恐惧学习和应激敏感至关重要。我们的实验室先前表明，NPY减少ta诱发的突触反应，然而，介导这种减少的NPY受体亚型尚不清楚。在这里，我们证明了在小鼠中外源性（浴敷）和内源性释放的NPY在TA通路中通过Y1受体起作用。这是首次证明Y1受体介导的对CA1突触功能的影响。有趣的是，NPY的慢性过度表达（在表达NPY的中间神经元中）会损害ta诱发的突触反应对Y1受体激动剂的敏感性。然而，众所周知的NPY Y2受体介导的Schaffer侧枝通路的作用不受NPY过表达的影响。因此，NPY可以通过NPY受体的差异表达及其对NPY过表达的反应对CA1突触传递产生通路特异性影响。我们的研究结果表明，NPY在TA通路中作用于Y1受体，这与TA通路是NPY在CA1中抗焦虑作用的基础的观点是一致的。

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引用次数: 0

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