Neuropeptides最新文献_第2页

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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引用次数: 0

Neuropeptide Y Y2 receptors in acute and chronic pain and itch 神经肽 Y Y2 受体在急性和慢性疼痛和瘙痒中的作用。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-10-18 DOI: 10.1016/j.npep.2024.102478

Paramita Basu , Bradley K. Taylor

Pain and itch are regulated by a diverse array of neuropeptides and their receptors in superficial laminae of the spinal cord dorsal horn (DH). Neuropeptide Y (NPY) is normally expressed on DH neurons but not sensory neurons. By contrast, the Npy2r receptor (Y2) is expressed on the central and peripheral terminals of sensory neurons but not on DH neurons. Neurophysiological slice recordings indicate that Y2-selective agonists inhibits spinal neurotransmitter release from sensory neurons. However, behavioral pharmacology studies indicate that Y2 agonists exert minimal changes in nociception, even after injury. Additional discrepancies in the behavioral actions of the Y2-antagonist BIIE0246 – reports of either pronociception or antinociception – have now been resolved. In the normal state, spinally-directed (intrathecal) administration of BIIE0246 elicits ongoing nociception, hypersensitivity to sensory stimulation, and aversion. Conversely, in the setting of nerve injury and inflammation, intrathecal BIIE024 reduced not only mechanical and thermal hypersensitivity, but also a measure of the affective dimension of pain (conditioned place preference). When administered in chronic pain models of latent sensitization, BIIE0246 produced a profound reinstatement of pain-like behaviors. We propose that tissue or nerve injury induces a G protein switch in the action of NPY-Y2 signaling from antinociception in the naïve state to the inhibition of mechanical and heat hyperalgesia in the injured state, and then a switch back to antinociception to keep LS in a state of remission. This model clarifies the pharmacotherapeutic potential of Y2 research, pointing to the development of a new non-opioid pharmacotherapy for chronic pain using Y2 antagonists in patients who do not develop LS.

疼痛和瘙痒是由脊髓背角（DH）浅层的多种神经肽及其受体调节的。神经肽 Y（NPY）通常在 DH 神经元上表达，但不在感觉神经元上表达。相比之下，Npy2r 受体（Y2）表达于感觉神经元的中枢和外周末梢，但不表达于 DH 神经元。神经电生理切片记录表明，Y2 选择性激动剂会抑制感觉神经元释放脊髓神经递质。然而，行为药理学研究表明，Y2 激动剂对痛觉的改变微乎其微，即使在损伤后也是如此。Y2-拮抗剂 BIIE0246 在行为学作用上的其他差异--关于代痛觉或抗痛觉的报告--现已得到解决。在正常状态下，脊髓定向（鞘内）给药 BIIE0246 会引起持续的痛觉、感觉刺激过敏和厌恶。相反，在神经损伤和炎症的情况下，鞘内注射 BIIE024 不仅能降低机械和热超敏反应，还能降低疼痛的情感维度（条件性位置偏好）。在慢性疼痛潜敏化模型中给药时，BIIE0246能显著恢复类似疼痛的行为。我们认为，组织或神经损伤会诱导 G 蛋白切换 NPY-Y2 信号的作用，从幼稚状态下的抗痛觉到损伤状态下机械和热超敏痛觉的抑制，然后再切换回抗痛觉以保持 LS 处于缓解状态。这一模型阐明了Y2研究的药物治疗潜力，并指出可以利用Y2拮抗剂开发一种新的非阿片类药物疗法，用于治疗未发展为LS的慢性疼痛患者。

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引用次数: 0

NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model 阻断 NK1 受体可破坏三维鼠乳腺癌模型中微肿瘤的生长和聚集

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-10-16 DOI: 10.1016/j.npep.2024.102479

Silvia Gutierrez, M. Danilo Boada

Several data indicate that Substance P (SP) neurokinin type 1 receptor (NK1R) is at the center of the interaction between cancer cells and peripheral sensory neurons. Selecting the appropriate cancer cell line and its susceptibility to being modulated by NK1 antagonists are critical to studying this complex interaction. In the current study, we have focused on this selection by comparing several aspects of the triple-negative breast cancer (TNBC) cell line (MDA-MB-231^LUC+) with a modified murine cell line (E0771^LUC+), both expressing luciferase. This comparison was made using several methods, SP stimulation and 3D cell culture models, to better reproduce the heterogenous microenvironment of solid tumors observed in vivo. Furthermore, the susceptibility of the murine cell line (E0771^LUC+) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771^LUC+ recapitulates several essential aspects of the human cell line, rendering this murine line ideal to be used on immune-competent animals during in vivo studies. We have also found that both cell lines are susceptible to SP stimulation, and their proliferation is disrupted by NK1R antagonists (Aprepitant). In vivo studies are required to verify and refine these findings.

一些数据表明，P 物质（SP）神经激肽 1 型受体（NK1R）是癌细胞与外周感觉神经元之间相互作用的中心。选择合适的癌细胞系及其对 NK1 拮抗剂的敏感性是研究这种复杂相互作用的关键。在目前的研究中，我们通过比较三阴性乳腺癌（TNBC）细胞系（MDA-MB-231LUC+）和改良鼠细胞系（E0771LUC+）的几个方面，重点研究了这一选择问题。这种比较采用了多种方法，包括 SP 刺激和三维细胞培养模型，以更好地再现体内观察到的实体瘤的异质微环境。此外，还测试了小鼠细胞系（E0771LUC+）对 NK1R 拮抗剂（Aprepitant）的敏感性。我们的研究结果表明，E0771LUC+ 重现了人类细胞系的几个重要方面，因此这种鼠细胞系非常适合在体内研究中用于免疫功能正常的动物。我们还发现，这两种细胞系都易受 SP 刺激，NK1R 拮抗剂（Aprepitant）会破坏它们的增殖。要验证和完善这些发现，还需要进行体内研究。

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引用次数: 0

Enteroendocrine cell-derived peptide YY signalling is stimulated by pinolenic acid or Intralipid and involves coactivation of fatty acid receptors FFA1, FFA4 and GPR119 蒎烯酸或 Intralipid 可刺激肠内分泌细胞衍生的肽 YY 信号，并涉及脂肪酸受体 FFA1、FFA4 和 GPR119 的协同激活。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-10-11 DOI: 10.1016/j.npep.2024.102477

Iain R. Tough, Runisha Moodaley, Helen M. Cox

Long chain fatty acids are sensed by enteroendocrine L cells that express free-fatty acid receptors, including FFA1, FFA4 and the acylethanolamine receptor GPR119. Here we investigated the acute effects of single or multiple agonism at these G protein-coupled receptors in intestinal mucosae where L cell-derived peptide YY (PYY) is anti-secretory and acts via epithelial Y₁ receptors. Mouse ileal or colonic mucosae were mounted in Ussing chambers, voltage-clamped and the resultant short-circuit current (I_sc) recorded continuously. The agonists used were; FFA1, TAK-875 or AM-1638; for FFA4, Merck A; or for GPR119, AR231453, PSN632408 or AR440006. Their responses were compared with those of pinolenic acid (PA, a presumed dual FFA1/FFA4 agonist) and the lipid emulsion, Intralipid. The FFA1 agonist AM-1638 (EC₅₀ = 38.2 nM) was more potent than TAK-875 (EC₅₀ = 203.1 nM) but exhibited similar efficacy. GPR119 agonism (AR231453) pretreatment enhanced subsequent FFA1 (AM-1638 or TAK-875) and FFA4 (Merck A) signalling. PA (EC₅₀ = 298.2 nM) co-activated epithelial FFA1 and FFA4 and involved endogenous PYY Y₁/Y₂-receptor mechanisms but desensitisation was observed between PA and high GPR119 agonist concentrations. Apical Intralipid co-activated FFA1, FFA4 and GPR119 with a residual component not being attributable to PYY, or this trio of fatty acid receptors.

长链脂肪酸由表达游离脂肪酸受体（包括 FFA1、FFA4 和酰乙醇胺受体 GPR119）的肠内分泌 L 细胞感知。在此，我们研究了单次或多次激动这些 G 蛋白偶联受体对肠粘膜的急性影响，其中 L 细胞衍生的肽 YY（PYY）具有抗分泌作用，并通过上皮 Y1 受体发挥作用。将小鼠回肠或结肠粘膜装入乌星室，进行电压钳夹，并连续记录由此产生的短路电流（Isc）。使用的激动剂有：FFA1，TAK-875 或 AM-1638；FFA4，默克 A；或 GPR119，AR231453、PSN632408 或 AR440006。将它们的反应与松脂酸（PA，一种假定的 FFA1/FFA4 双激动剂）和脂质乳液 Intralipid 的反应进行了比较。FFA1激动剂AM-1638（EC50 = 38.2 nM）比TAK-875（EC50 = 203.1 nM）更有效，但药效相似。GPR119 激动剂（AR231453）预处理增强了随后的 FFA1（AM-1638 或 TAK-875）和 FFA4（默克 A）信号传导。PA（EC50 = 298.2 nM）共同激活上皮 FFA1 和 FFA4，并涉及内源性PYY Y1/Y2 受体机制，但在 PA 和高浓度 GPR119 激动剂之间观察到脱敏现象。Apical Intralipid 可共同激活 FFA1、FFA4 和 GPR119，其残余部分不归因于PYY 或这三种脂肪酸受体。

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引用次数: 0

Adrenomedullin-mediated depressor response with visceral afferent-specific membrane depolarization in isolated nodose ganglion neurons from adult female rat 成年雌鼠离体结节神经元中肾上腺髓质素介导的内脏传入特异性膜去极化抑制反应

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-10-10 DOI: 10.1016/j.npep.2024.102476

Yan Feng , Ying Li , Hua Liu

Adrenomedullin (ADM) is an endogenous and vasoactive neuropeptide that possesses potent central/peripheral regulations on blood pressure (BP) and sex-related vasodilation under physiological conditions. However, the role of ADM on baroreflex afferent function is largely unknown. Here, BP was monitored in adult female rats while ADM was microinjected into the nodose ganglion (NG); Fluorescent intensity against ADM was analyzed in the tissue level and membrane responses elicited by ADM were tested in identified NG neurons isolated from adult female rats with gap-free protocol under current-clamp mode with or without ADM antagonist. The results showed that BP was reduced by ADM (30–300 nM) concentration-dependently; myelinated (HCN1-positive) neurons showed significantly higher fluorescent intensity against ADM antibody vs. unmyelinated (HCN1-negative) neurons. Interestingly, patch-clamp data indicated that membrane potential was not changed in 50 % (6/12) of identified A-types, only 4/12 was hyperpolarized by 30 nM ADM, while 100 nM ADM induced brief hyperpolarization followed by depolarization in 2/12 of recordings; Robustly, ADM depolarized 100 % tested myelinated Ah-type neurons with dramatic and concentration-dependent repetitive discharges; While, a majority (8/9) of unmyelinated C-types were depolarized and few with repetitive dischargers. By application of ADM (22–52), the depolarization elicited by ADM 100 nM was partially or completely abolished in Ah-types or C-types, respectively. These datasets demonstrated for the first time that baroreflex afferents especially female-distributed subpopulation of Ah-types would be a key player in ADM-mediated depressor response unveiling the dominate role of peripheral ADM in neurocontrol of hypotension via baroreflex afferent function and gender-dependent vasodilation promoted by female sex steroid.

肾上腺髓质素（ADM）是一种具有血管活性的内源性神经肽，在生理条件下对血压（BP）和与性别相关的血管扩张具有强有力的中枢/外周调节作用。然而，ADM 对气压反射传入功能的作用在很大程度上是未知的。在此，研究人员向成年雌性大鼠的结节神经节（NG）微注射了ADM，同时监测了大鼠的血压；在组织水平分析了针对ADM的荧光强度，并在电流钳模式下使用或不使用ADM拮抗剂，通过无间隙方案检测了从成年雌性大鼠身上分离出的NG神经元中ADM引起的膜反应。结果表明，ADM（30-300 nM）浓度依赖性地降低了血压；与无髓鞘（HCN1 阴性）神经元相比，有髓鞘（HCN1 阳性）神经元对 ADM 抗体的荧光强度明显更高。有趣的是，膜片钳数据显示，50%（6/12）的已识别 A 型神经元的膜电位没有发生变化，只有 4/12 的神经元在 30 nM ADM 的作用下发生超极化，而在 2/12 的记录中，100 nM ADM 会诱导短暂的超极化，随后发生去极化；ADM能使100%接受测试的有髓鞘的AH型神经元去极化，并产生显著的、浓度依赖性的重复放电；而大多数（8/9）无髓鞘的C型神经元去极化，只有极少数产生重复放电。应用 ADM（22-52）后，Ah 型或 C 型神经元分别部分或完全消除了 ADM 100 nM 引起的去极化。这些数据集首次证明了气压反射传入，尤其是雌性分布的 Ah 型亚群在 ADM 介导的降压反应中起着关键作用，揭示了外周 ADM 通过气压反射传入功能和雌性激素促进的性别依赖性血管扩张在低血压神经控制中的主导作用。

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引用次数: 0

Lipid metabolism: Novel approaches for managing idiopathic epilepsy 脂质代谢：治疗特发性癫痫的新方法。

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-29 DOI: 10.1016/j.npep.2024.102475

Chao Wang, Jinxia Zhai, Xuemei Zhou, Yongjun Chen

Epilepsy is a common neurological condition characterized by abnormal neuronal activity, often leading to cellular damage and death. There is evidence to suggest that lipid imbalances resulting in cellular death play a key role in the development of epilepsy, including changes in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Disrupted lipid metabolism acts as a crucial pathological mechanism in epilepsy, potentially linked to processes such as cellular ferroptosis, lipophagy, and immune modulation of gut microbiota (thus influencing the gut-brain axis). Understanding these mechanisms could open up new avenues for epilepsy treatment. This study investigates the association between disturbances in lipid metabolism and the onset of epilepsy.

癫痫是一种常见的神经系统疾病，其特点是神经元活动异常，常常导致细胞损伤和死亡。有证据表明，导致细胞死亡的脂质失衡在癫痫发病中起着关键作用，包括甘油三酯、胆固醇、鞘脂、磷脂、脂滴和胆汁酸（BAs）的变化。脂质代谢紊乱是癫痫的一个重要病理机制，可能与细胞铁凋亡、脂质吞噬和肠道微生物群的免疫调节（从而影响肠道-大脑轴）等过程有关。了解这些机制可为癫痫治疗开辟新途径。本研究探讨了脂质代谢紊乱与癫痫发病之间的关联。

引用次数: 0

Physiologically relevant lactate accumulation from exercise or peripheral injection does not alter central or peripheral appetite signaling in mice 运动或外周注射造成的与生理相关的乳酸积累不会改变小鼠的中枢或外周食欲信号传导

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-19 DOI: 10.1016/j.npep.2024.102473

Seth F. McCarthy , Michael S. Finch , Rebecca E.K. MacPherson , Tom J. Hazell

Lactate has been implicated in exercise-induced appetite suppression though little work has explored the mechanisms underpinning its role. Recent work suggests lactate accumulation via exercise and intracerebroventricular injection can alter central appetite regulating pathways, though a supraphysiological dose of lactate was administered centrally and there was no assessment of peripheral appetite markers. Therefore, we examined how physiologically relevant lactate accumulation via exercise or intraperitoneal injection altered central and peripheral appetite signaling pathways and whether the lactate dehydrogenase inhibitor oxamate could blunt any exercise effect. Forty 10-week-old C57BL/6 J male mice (n = 10/group) were assigned to either: 1) sedentary (SED + SAL; saline); 2) exercise (EX+SAL; saline); 3) exercise with oxamate (EX+OX; 750 mg‧kg⁻¹ body mass); or 4) lactate (SED + LAC; 1.0 g‧kg⁻¹ body mass). Blood, stomach, and hypothalamus samples were collected ∼2 h post-exercise/injection. Though oxamate blunted exercise-induced lactate accumulation compared to the EX+SAL condition (P = 0.044, d = 0.73), there were no differences in circulating acylated ghrelin or stomach ghrelin O-acyltransferase content between groups (P > 0.213,

η_{p}^{2}

<0.125). There were also no differences in hypothalamic content for neuropeptide Y, proopiomelanocortin, agouti-related peptide, and alpha melanocyte-stimulating hormone (P > 0.150,

η_{p}^{2}

<0.170). Exercise did increase phosphorylated-total signal transducer and activator of transcription 3 (pSTAT3) compared to EX+OX (p = 0.065, d = 1.23) but there were no differences in other markers of lactate signaling: phosphorylated-total adenosine monophosphate activated protein kinase, and protein kinase b (P > 0.121,

η_{p}^{2}

<0.160). Our results suggest that lactate accumulation due to exercise or peripheral injection does not alter central or peripheral appetite signaling when measured 2 h post-exercise/injection, though pSTAT3 was blunted with oxamate.

乳酸盐与运动引起的食欲抑制有关，但很少有研究探讨其作用机制。最近的研究表明，通过运动和脑室内注射进行乳酸盐蓄积可改变中枢食欲调节途径，但乳酸盐是超生理剂量的，而且没有对外周食欲标记物进行评估。因此，我们研究了通过运动或腹腔注射造成的生理学相关乳酸累积如何改变中枢和外周食欲信号通路，以及乳酸脱氢酶抑制剂草酸盐是否能减弱任何运动效应。40只10周大的C57BL/6 J雄性小鼠（n = 10/组）被分配到以下任一组：1）静坐（SED + SAL；生理盐水）；2）运动（EX+SAL；生理盐水）；3）含草酸盐的运动（EX+OX；750 mg‧kg-1体重）；或4）乳酸盐（SED + LAC；1.0 g‧kg-1体重）。运动/注射后 2 小时采集血液、胃和下丘脑样本。虽然与 EX+SAL 条件相比，草氨酸盐能减弱运动诱导的乳酸累积（P = 0.044，d = 0.73），但不同组间的循环酰化胃泌素或胃泌素 O-酰基转移酶含量没有差异（P > 0.213，ηp2<0.125）。下丘脑中的神经肽 Y、前黑皮素、激动相关肽和α-黑素细胞刺激素含量也没有差异（P> 0.150, ηp2<0.170）。与 EX+OX 相比，运动确实增加了磷酸化-信号转导子和转录激活子 3（pSTAT3）的总量（P = 0.065，d = 1.23），但乳酸信号转导的其他标记物：磷酸化-单磷酸腺苷激活的蛋白激酶总量和蛋白激酶 b（P > 0.121，ηp2<0.160）并无差异。我们的结果表明，运动或外周注射导致的乳酸积聚不会改变运动/注射后 2 小时的中枢或外周食欲信号传导，尽管草氨酸会减弱 pSTAT3。

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引用次数: 0

GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA GnRH对AANAT-siRNA诱导的长期延时损伤的保护作用

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides

Pub Date : 2024-09-18 DOI: 10.1016/j.npep.2024.102474

Leila Karimi-Zandi , Tahereh Ghorbandaiepour , Maryam Zahmatkesh , Esmaeil Sadroddiny

There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.

Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.

GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.

促性腺激素释放激素（GnRH）和褪黑激素能系统之间存在相互作用。褪黑激素合成的关键酶（芳基烷基胺 N-乙酰转移酶，AANAT）和促性腺激素释放激素受体都在海马中表达。有研究表明，海马 AANAT 酶的活性是海马正常认知功能所必需的，但它们在长期延时（LTP）诱导中的作用尚未完全明了。本研究在抑制海马褪黑激素合成的同时，研究了GnRH对LTP诱导的影响。通过AANAT-siRNA抑制褪黑激素的合成，并使用体内场电位电生理记录诱导LTP。动物被分为 5 组：动物分为 5 组：完整组、载体组、siRNA 组、GnRH 组和 siRNA+GnRH 组。除完整组外，所有动物均接受立体定向手术和海马内插管，分别接受载体、AANAT siRNA（0.5 μg/hip）、GnRH（1 ng/rat）和AANAT siRNA+GnRH。识别记忆通过新物体识别测试进行评估。场电位电生理学实验通过刺激沙弗侧路进行，LTP诱导通过高频刺激（HFS）进行。记录结束后，动物大脑被分离并快速冷冻，以进一步通过LC-MS测定海马褪黑激素水平，并通过qRT-PCR测定AANAT mRNA水平。在海马中注射 GnRH 增加了局部 AANAT mRNA 的表达和褪黑激素水平。经GnRH处理的动物的LTP振幅高于完整组、车辆组和siRNA组。AANAT-siRNA 降低了海马褪黑激素水平，抑制了 LTP 并损害了识别记忆，而 GnRH 则防止了这些不利影响。这些数据表明，GnRH对AANAT-siRNA诱导的LTP下降具有保护作用。这种保护机制至少部分可能与局部 AANAT-mRNA 表达的增加有关。

{"title":"GnRH protective effects against long-term potentiation impairment induced by AANAT-siRNA","authors":"Leila Karimi-Zandi , Tahereh Ghorbandaiepour , Maryam Zahmatkesh , Esmaeil Sadroddiny","doi":"10.1016/j.npep.2024.102474","DOIUrl":"10.1016/j.npep.2024.102474","url":null,"abstract":"<div><div>There is an interplay between the gonadotropin-releasing hormone (GnRH) and melatoninergic systems. The key enzyme of melatonin synthesis (arylalkylamine <em>N</em>-acetyltransferase, AANAT), and GnRH receptors are expressed in the hippocampus. While it has been shown that hippocampal AANAT enzyme activity is necessary for proper hippocampal cognitive function, their role in long-term potentiation (LTP) induction is not fully understood. In current study, the impact of GnRH on LTP induction was investigated, while hippocampal melatonin synthesis had been inhibited. The melatonin synthesis was inhibited by AANAT-siRNA administration, and LTP was induced using in vivo field potential electrophysiological recording.</div><div>Animals were divided into 5 groups: Intact, vehicle, siRNA, GnRH and siRNA+GnRH. All animals, except intact group, experienced the stereotaxic surgery and intra-hippocampal cannulation to receive vehicle agent, AANAT siRNA (0.5 μg/hip), GnRH (1 ng/rat), and AANAT siRNA+GnRH. The recognition memory was assessed by Novel object recognition test. The field potential electrophysiology experiment was conducted by stimulating the Schaffer collateral pathway, and LTP induction was carried out through high-frequency stimulation (HFS). After recording, animals' brain was isolated and quickly frozen for further hippocampal melatonin levels measurement by LC-MS and AANAT mRNA levels by qRT-PCR.</div><div>GnRH injection in the hippocampus increased local AANAT-mRNA expression and melatonin levels. GnRH-treated animals displayed higher LTP amplitude compared to intact, vehicle and siRNA groups. While the reduction in hippocampal melatonin levels by AANAT-siRNA inhibited LTP and impaired recognition memory, the GnRH prevented these adverse effects. The data suggests that GnRH have protective effects against AANAT-siRNA-induced LTP decline. The protective mechanism at least partially, may be related to the increased expression of local AANAT-mRNA.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102474"},"PeriodicalIF":2.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292235","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}

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