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The persistence of changes in insulin sensitivity and metabolic gene expression after acute exercise in male and female mice 雄性和雌性小鼠急性运动后胰岛素敏感性和代谢基因表达的持续变化
IF 1.7 Q3 PHYSIOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.crphys.2025.100170
Jack H. Thompson, Alexa M. Fooskas, Erica J. Locke, Renee N. Washart, Alexandria M. Chin, Paige A.P. Ponzo, Joshua Oduwole, Nicholas DiGiuseppe, Max Matalavage, Stephen C. Kolwicz Jr.

Background

Acute exercise has been suggested to increase insulin sensitivity, although the duration of the improvement may last anywhere from 4 to 72 h. In addition, changes in gene expression in response to exercise is suggested to last at least 24 h. Despite this, exercise training studies assess metabolism anywhere from immediately after to 72 h after the last exercise session, which could confuse the acute versus chronic exercise effects. Therefore, the purpose of this study was to assess the duration of changes in insulin sensitivity after acute exercise and the impact of acute exercise on metabolic gene expression.

Materials and methods

Male and female mice endured a single bout of aerobic exercise and underwent insulin sensitivity tests at 30 min, 4 h, and 24 h following acute exercise. Furthermore, skeletal muscle was harvested, and gene expression analysis was performed at 30 min and 24, 48, and 72 h after the exercise bout.

Results

Females had increased insulin sensitivity compared to males independent of exercise. However, males showed increased sensitivity 30 min following exercise while females did not. Neither males nor females had improved insulin sensitivity 24 h following exercise. Both male and female mice had upregulation of several metabolic genes 24 h after acute exercise, which was comparable to sedentary controls after 48–72 h of recovery.

Conclusions

The results show that acute exercise does not significantly affect insulin sensitivity 24 h after exercise but the effects of acute exercise on metabolic gene expression persist after 24 h and return to baseline within 48–72 h.
研究表明,急性运动可以增加胰岛素敏感性,尽管改善的持续时间可能从4到72小时不等。此外,运动后基因表达的变化被认为至少持续24小时。尽管如此,运动训练研究评估的是最后一次运动后立即到72小时的任何地方的代谢,这可能会混淆急性和慢性运动的影响。因此,本研究的目的是评估急性运动后胰岛素敏感性变化的持续时间以及急性运动对代谢基因表达的影响。材料和方法雄性和雌性小鼠进行单次有氧运动,并在急性运动后30分钟、4小时和24小时进行胰岛素敏感性测试。此外,采集骨骼肌,并在运动后30分钟、24、48和72小时进行基因表达分析。结果与独立运动的男性相比,女性的胰岛素敏感性增加。然而,运动后30分钟,男性的敏感性有所提高,而女性则没有。运动后24小时,男性和女性的胰岛素敏感性都没有改善。在剧烈运动后24小时,雄性和雌性小鼠的几个代谢基因都出现了上调,在48-72小时的恢复后,这与久坐对照组相当。结论急性运动对运动后24 h胰岛素敏感性无显著影响,但对代谢基因表达的影响在24 h后持续存在,并在48 ~ 72 h内恢复到基线水平。
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引用次数: 0
How PPAR-alpha mediated inflammation may affect the pathophysiology of chronic kidney disease PPAR-α 介导的炎症如何影响慢性肾病的病理生理学
IF 2.1 Q3 PHYSIOLOGY Pub Date : 2024-11-14 DOI: 10.1016/j.crphys.2024.100133
Sepiso K. Masenga , Selam Desta , Mark Hatcher , Annet Kirabo , Dexter L. Lee
Chronic kidney disease (CKD) is a major risk factor for death in adults. Inflammation plays a role in the pathogenesis of CKD, but the mechanisms are poorly understood. Peroxisome proliferator-activated receptor alpha (PPAR-α) is a nuclear receptor and one of the three members (PPARα, PPARβ/δ, and PPARγ) of the PPARs that plays an important role in ameliorating pathological processes that accelerate acute and chronic kidney disease. Although other PPARs members are well studied, the role of PPAR-α is not well described and its role in inflammation-mediated chronic disease is not clear. Herein, we review the role of PPAR-α in chronic kidney disease with implications for the immune system.
慢性肾脏病(CKD)是成年人死亡的主要风险因素。炎症在慢性肾脏病的发病机制中起着一定的作用,但对其机制却知之甚少。过氧化物酶体增殖激活受体α(PPAR-α)是一种核受体,也是 PPARs 三大成员(PPARα、PPARβ/δ 和 PPARγ)之一,在改善加速急性和慢性肾病的病理过程中发挥着重要作用。虽然对 PPARs 的其他成员进行了深入研究,但 PPAR-α 的作用尚未得到很好的描述,其在炎症介导的慢性疾病中的作用也不明确。在此,我们回顾了 PPAR-α 在慢性肾病中的作用以及对免疫系统的影响。
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引用次数: 0
Cell-based homologous expression system for in-vitro characterization of environmental effects on transmembrane peptide transport in fish 基于细胞的同源表达系统,用于体外鉴定环境对鱼类跨膜肽转运的影响
Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100118
Pazit Con , Jens Hamar , Jakob Biran , Dietmar Kültz , Avner Cnaani

All organisms encounter environmental changes that lead to physiological adjustments that could drive evolutionary adaptations. The ability to adjust performance in order to cope with environmental changes depends on the organism's physiological plasticity. These adjustments can be reflected in behavioral, physiological, and molecular changes, which interact and affect each other. Deciphering the role of molecular adjustments in physiological changes will help to understand how multiple levels of biological organization are synchronized during adaptations. Transmembrane transporters, which facilitate a cell's interaction with its surroundings, are prime targets for molecular studies of the environmental effects on an organism's physiology. Fish are subjected to environmental fluctuations and exhibit different coping mechanisms. To study the molecular adjustments of fish transporters to their external surrounding, suitable experimental systems must be established. The Mozambique tilapia (Oreochromis mossambicus) is an excellent model for environmental stress studies, due to its extreme salinity tolerance. We established a homologous cellular-based expression system and uptake assay that allowed us to study the effects of environmental conditions on transmembrane transport. We applied our expression system to investigate the effects of environmental conditions on the activity of PepT2, a transmembrane transporter critical in the absorption of dietary peptides and drugs. We created a stable, modified fish cell-line, in which we exogenously expressed the tilapia PepT2, and tested the effects of water temperature and salinity on the uptake of a fluorescent di-peptide, β-Ala-Lys-AMCA. While temperature affected only Vmax, medium salinity had a bi-directional effect, with significantly reduced Vmax in hyposaline conditions and significantly increased Km in hypersaline conditions. These assays demonstrate the importance of suitable experimental systems for fish ecophysiology studies. Furthermore, our in-vitro results show how the effect of hypersaline conditions on the transporter activity can explain expression shifts seen in the intestine of saltwater-acclimated fish, emphasizing the importance of complimentary studies in better understanding environmental physiology. This research highlights the advantages of using homologous expression systems to study environmental effects encountered by fish, in a relevant cellular context. The presented tools and methods can be adapted to study other transporters in-vitro.

所有生物都会遇到环境变化,从而导致生理调整,进而推动进化适应。调整性能以应对环境变化的能力取决于生物的生理可塑性。这些调整可以反映在行为、生理和分子变化上,而这些变化是相互作用和相互影响的。破译分子调整在生理变化中的作用将有助于了解生物组织的多个层次在适应过程中是如何同步进行的。跨膜转运体可促进细胞与周围环境的相互作用,是研究环境对生物生理影响的分子研究的主要目标。鱼类会受到环境波动的影响,并表现出不同的应对机制。要研究鱼类转运体对外界环境的分子调节,必须建立合适的实验系统。莫桑比克罗非鱼(Oreochromis mossambicus)具有极强的耐盐性,是研究环境压力的绝佳模型。我们建立了一个基于细胞的同源表达系统和摄取检测方法,使我们能够研究环境条件对跨膜转运的影响。我们应用我们的表达系统研究了环境条件对 PepT2 活性的影响,PepT2 是一种跨膜转运体,对膳食肽和药物的吸收至关重要。我们创建了一个稳定的改良鱼细胞系,在其中外源表达罗非鱼 PepT2,并测试了水温和盐度对荧光二肽 β-Ala-Lys-AMCA 吸收的影响。温度只影响Vmax,而中盐度则具有双向影响,在低盐度条件下Vmax显著降低,而在高盐度条件下Km显著增加。这些实验证明了合适的实验系统对鱼类生态生理学研究的重要性。此外,我们的体外实验结果表明,低盐条件对转运体活性的影响可以解释盐水适应性鱼类肠道中的表达变化,强调了辅助研究对更好地理解环境生理学的重要性。这项研究强调了利用同源表达系统在相关细胞环境中研究鱼类所受环境影响的优势。介绍的工具和方法可用于体外研究其他转运体。
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引用次数: 0
Effect of a cajuína hydroelectrolytic drink on the physical performance and hydration status of recreational runners 水苏碱水电解饮料对休闲跑步者运动表现和水合状态的影响
Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100119
Valmir Oliveira Silvino , Mara Cristina Carvalho Batista , Manoel Miranda Neto , André Luiz Berzoti Ribeiro , Paulo Pedro do Nascimento , Esmeralda Maria Lustosa Barros , Rayane Carvalho de Moura , Karen Christie Gomes Sales , Luanne Morais Vieira Galvão , Lívio César Cunha Nunes , Alessandra Durazzo , Alexandre Sérgio Silva , Marcos Antonio Pereira dos Santos

Cajuína is a processed drink derived from cashew and is widely consumed in the northeast region of Brazil. This study evaluated the effect of a cajuína-based hydroelectrolytic drink on the aerobic performance and hydration status of recreational runners. Seventeen males (31.9 ± 1.6 years, 51.0 ± 1.4 ml/kg/min) performed three time-to-exhaustion running sessions on a treadmill at 70% VO2max, ingesting cajuína hydroelectrolytic drink (CJ), high carbohydrate commercial hydroelectrolytic drink (CH) and mineral water (W) every 15 min during the running test. The participants ran 80.3 ± 8.4 min in CJ, 70.3 ± 6.8 min in CH and 71.8 ± 6.9 min in W, with no statistical difference between procedures. Nevertheless, an effect size of η2 = 0.10 (moderate) was observed. No statistical difference was observed in the concentrations of sodium, potassium, and osmolality in both serum and urine between the three conditions. However, the effect size was moderate (urine sodium) and high (serum sodium, potassium, and osmolality). Urine specific gravity, sweating rate and heart rate were not significantly different between drinks. The cajuína-based hydroelectrolytic drink promotes similar effects compared to commercial hydroelectrolytic drink and water, considering specific urine gravity, heart rate, sweating, and time to exhaustion in recreational runners.

Cajuína 是一种从腰果中提取的加工饮料,在巴西东北部地区被广泛饮用。本研究评估了卡朱伊纳水电解饮料对休闲跑步者有氧运动表现和水合状态的影响。17 名男性(31.9±1.6 岁,51.0±1.4 毫升/千克/分钟)在跑步机上以 70% VO2max 的速度进行了三次耗时耗力跑步测试,在跑步测试期间每 15 分钟摄入一次水苏碱水电解饮料(CJ)、高碳水化合物商业水电解饮料(CH)和矿泉水(W)。参试者饮用 CJ 后的跑步时间为 80.3 ± 8.4 分钟,饮用 CH 后的跑步时间为 70.3 ± 6.8 分钟,饮用 W 后的跑步时间为 71.8 ± 6.9 分钟。不过,观察到的效应大小为 η2 = 0.10(中等)。在三种条件下,血清和尿液中的钠、钾和渗透压浓度均无统计学差异。然而,影响大小为中度(尿钠)和高度(血清钠、钾和渗透压)。不同饮料之间的尿比重、出汗率和心率没有显著差异。考虑到休闲跑步者的尿比重、心率、出汗率和体力耗尽时间,水苏碱水电解饮料与商业水电解饮料和水相比具有相似的效果。
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引用次数: 0
Immediate effects of passion fruit juice supplementation on working ability and attention in healthy participants 补充百香果汁对健康参与者工作能力和注意力的直接影响
Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100120
Piyapong Prasertsri , Kittiya Sinnitithavorn , Chonlakan Raroengjai , Rujirat Phichayaworawit , Pimonpan Taweekarn , Kunavut Vannajak , Uraiporn Booranasuksakul

This study investigated the effects of a single consumption of passion fruit juice (PFJ) on working ability and attention. It included 14 healthy participants aged 20–30 years. Participants randomly consumed either placebo or 50% PFJ at 3.5 mL/kg body mass. Each intervention was divided into two phases (before and after consumption). Before consumption, the participants underwent blood glucose, blood pressure, and heart rate examinations. Then, working ability and attention were evaluated. Thereafter, the blood glucose, blood pressure, and heart rate were repeatedly examined. Next, the participants completed consumption. After consumption, the participants underwent the same experiments performed before consumption. The total working ability scores after consumption were significantly high in both interventions (P < 0.05). However, PFJ intervention had a significantly higher working ability at 1, 2, 3, 4, and 5 min than placebo intervention (P < 0.05). Moreover, PFJ intervention had greater increases in attention than placebo intervention. There were no significant differences in attention between two interventions. The blood glucose levels were significantly lower in PFJ intervention than in placebo intervention both before the working ability test and after the attention test (P < 0.05). A single consumption of PFJ improved working ability in healthy participants. This may be enhanced by improving attentional focus and maintaining postprandial blood glucose.

本研究调查了单次饮用百香果汁(PFJ)对工作能力和注意力的影响。研究对象包括 14 名 20-30 岁的健康参与者。参与者随机饮用安慰剂或 50%的百香果汁(3.5 毫升/千克体重)。每次干预分为两个阶段(饮用前和饮用后)。在服用前,参与者接受了血糖、血压和心率检查。然后,对工作能力和注意力进行评估。之后,反复检查血糖、血压和心率。接下来,受试者完成进食。进食后,参与者进行了与进食前相同的实验。在两种干预中,进食后的工作能力总分都明显较高(P <0.05)。然而,PFJ干预在1、2、3、4和5分钟的工作能力明显高于安慰剂干预(P <0.05)。此外,与安慰剂干预相比,PFJ干预对注意力的提高更大。两种干预方法在注意力方面没有明显差异。在工作能力测试前和注意力测试后,PFJ干预者的血糖水平都明显低于安慰剂干预者(P < 0.05)。单次饮用 PFJ 可提高健康参与者的工作能力。这可能是通过提高注意力和维持餐后血糖来实现的。
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引用次数: 0
Investigating the role of CFTR in human and mouse myometrium 研究 CFTR 在人类和小鼠子宫肌层中的作用
Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100122
Clodagh Prendergast, Susan Wray, Daniella Dungate, Christine Martin, Andra Vaida, Elizabeth Brook, Cecilia Ani Chioma, Helen Wallace

Background

Abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) has been linked to airway smooth muscle abnormalities including bronchial hyperresponsiveness. However, a role for CFTR in other types of smooth muscle, including myometrium, remains largely unexplored. As CF life expectancy and the number of pregnancies increases, there is a need for an understanding of the potential role of CFTR in myometrial function.

Methods

We investigated the role of CFTR in human and mouse myometrium. We used immunofluorescence to identify CFTR expression, and carried out contractility studies on spontaneously contracting term pregnant and non-pregnant mouse myometrium and term pregnant human myometrial biopsies from caesarean sections.

Results

CFTR was found to be expressed in term pregnant mouse myometrium. Inhibition of CFTR, with the selective inhibitor CFTRinh-172, significantly reduced contractility in pregnant mouse and human myometrium in a concentration-dependent manner (44.89 ± 11.02 term pregnant mouse, 9.23 ± 4.75 term-pregnant human; maximal effect at 60 μM expressed as a percentage of the pre-treatment control period). However, there was no effect of CFTRinh-172 in non-pregnant myometrium.

Conclusion

These results demonstrate decreased myometrial function when CFTR is inhibited, which may have implications on pregnancy and labour outcome and therapeutic decisions for labour in CF patients.

背景囊性纤维化(CF)中囊性纤维化跨膜传导调节因子(CFTR)功能异常与气道平滑肌异常(包括支气管高反应性)有关。然而,CFTR 在包括子宫肌层在内的其他类型平滑肌中的作用在很大程度上仍未得到探索。随着 CF 患者寿命的延长和妊娠次数的增加,有必要了解 CFTR 在子宫肌层功能中的潜在作用。我们使用免疫荧光技术鉴定了 CFTR 的表达,并对自发收缩的足月妊娠小鼠和非妊娠小鼠子宫肌层以及剖腹产足月妊娠人子宫肌层活检组织进行了收缩力研究。用选择性抑制剂 CFTRinh-172 抑制 CFTR 可显著降低妊娠小鼠和人类子宫肌层的收缩力,其影响呈浓度依赖性(44.89 ± 11.02 期妊娠小鼠,9.23 ± 4.75 期妊娠人类;60 μM 时的最大影响以处理前对照期的百分比表示)。这些结果表明,当 CFTR 受抑制时,子宫肌层功能会下降,这可能会对妊娠和分娩结果以及 CF 患者的分娩治疗决策产生影响。
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引用次数: 0
Glycophagy is involved in cardiac glycogen regulation in response to exercise 糖吞噬参与运动时的心糖原调节
IF 2.1 Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100131
Samuel L. James , Parisa Koutsifeli , Randall F. D'Souza , Stewart WC. Masson , Jonathan ST. Woodhead , Troy L. Merry , Lea MD. Delbridge , Kimberley M. Mellor

Cardiac glycogen-autophagy (‘glycophagy’) is disturbed in cardiometabolic pathologies. The physiological role of cardiac glycophagy is unclear. Exercise induces transient cardiac glycogen accumulation. Thus, this study experimentally examined glycophagy involvement during recovery from an exhaustive exercise protocol. Peak myocardial glycogen accumulation in mice was evident at 2 h post-exercise, preceded by transient activation of glycogen synthase. At 4 and 16 h post-exercise, glycogen degradation was associated with decreased STBD1 (glycophagy tagging protein) and increased GABARAPL1 (Atg8 protein), suggesting that glycophagy activity was increased. These findings provide the first evidence that glycophagy is involved in cardiac glycogen physiologic homeostasis post-exercise.

心脏糖原自噬("glycophagy")在心脏代谢性疾病中会受到干扰。心糖原自噬的生理作用尚不清楚。运动会诱发短暂的心糖原累积。因此,本研究通过实验检测了在从剧烈运动方案中恢复时糖吞噬的参与情况。小鼠心肌糖原累积的峰值在运动后 2 小时明显出现,之前糖原合成酶被短暂激活。运动后4小时和16小时,糖原降解与STBD1(糖吞噬标记蛋白)的减少和GABARAPL1(Atg8蛋白)的增加有关,这表明糖吞噬活性增加了。这些发现首次证明了糖吞噬参与了运动后心肌糖原的生理平衡。
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引用次数: 0
Effects of aerobic exercise during recovery from eccentric contraction on muscular performance, oxidative stress and inflammation 偏心收缩恢复期间的有氧运动对肌肉性能、氧化应激和炎症的影响
IF 2.1 Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100129

This study investigated the effects of aerobic exercise during recovery from eccentric contraction (EC) on muscular performance, oxidative stress, and inflammation. Nineteen male subjects between 18 and 29 years were divided into unexercised (control, n = 9) and exercised (n = 10) groups. Initially, the subjects performed EC as 3 sets until exhaustion with elbow flexion and extension on the Scott bench at 80% in 1RM, followed by four aerobic exercise sessions. The results obtained indicated (p > 0.05) that aerobic physical exercise during the recovery period does not improve muscle performance (isometric strength and muscular fatigue), oxidative stress parameters (lipid peroxidation, protein oxidation and antioxidant enzyme activity), and inflammatory cytokines (IL-1β, TNF-α, IL-10). In conclusion, the aerobic exercise during the recovery period does not alter the parameters of performance, oxidative stress and inflammation induced by the EC.

本研究调查了在偏心收缩(EC)恢复期间进行有氧运动对肌肉表现、氧化应激和炎症的影响。19名年龄在18至29岁之间的男性受试者被分为未锻炼组(对照组,n = 9)和锻炼组(n = 10)。起初,受试者在斯科特长凳上以 80% 的 1RM 进行肘关节屈伸运动,每组 3 次,直至筋疲力尽,然后进行 4 次有氧运动。结果表明(p >0.05),恢复期有氧运动并不能改善肌肉性能(等长力量和肌肉疲劳)、氧化应激参数(脂质过氧化、蛋白质氧化和抗氧化酶活性)和炎症细胞因子(IL-1β、TNF-α、IL-10)。总之,在恢复期进行有氧运动并不会改变由 EC 引起的运动表现、氧化应激和炎症参数。
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引用次数: 0
A new method for isolation and purification of fusion-competent inhibitory synaptic vesicles 分离和纯化具有融合能力的抑制性突触小泡的新方法
Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100121
Nisha Gopal , Jeremy Leitz , Chuchu Wang , Luis Esquivies , Richard A. Pfuetzner , Axel T. Brunger

Synaptic vesicles specific to inhibitory GABA-releasing neurons are critical for regulating neuronal excitability. To study the specific molecular composition, architecture, and function of inhibitory synaptic vesicles, we have developed a new method to isolate and purify GABA synaptic vesicles from mouse brains. GABA synaptic vesicles were immunoisolated from mouse brain tissue using an engineered fragment antigen-binding region (Fab) against the vesicular GABA transporter (vGAT) and purified. Western blot analysis confirmed that the GABA synaptic vesicles were specifically enriched for vGAT and largely depleted of contaminants from other synaptic vesicle types, such as vesicular glutamate transporter (vGLUT1), and other cellular organelles. This degree of purity was achieved despite the relatively low abundance of vGAT vesicles compared to the total synaptic vesicle pool in mammalian brains. Cryo-electron microscopy images of these isolated GABA synaptic vesicles revealed intact morphology with circular shape and protruding proteinaceous densities. The GABA synaptic vesicles are functional, as assessed by a hybrid (ex vivo/in vitro) vesicle fusion assay, and they undergo synchronized fusion with synthetic plasma membrane mimic vesicles in response to Ca2+-triggering, but, as a negative control, not to Mg2+-triggering. Our immunoisolation method could also be applied to other types of vesicles.

抑制性 GABA 释放神经元特异的突触小泡对于调节神经元的兴奋性至关重要。为了研究抑制性突触小泡的特定分子组成、结构和功能,我们开发了一种从小鼠大脑中分离和纯化 GABA 突触小泡的新方法。使用针对囊泡 GABA 转运体(vGAT)的工程化抗原结合区片段(Fab)从小鼠脑组织中免疫分离 GABA 突触小泡并进行纯化。Western 印迹分析证实,GABA 突触小泡特异性地富集了 vGAT,并在很大程度上清除了其他突触小泡类型(如囊泡谷氨酸转运体(vGLUT1))和其他细胞器的污染物。尽管与哺乳动物大脑中的突触小泡总量相比,vGAT 小泡的丰度相对较低,但这种纯度还是达到了。这些分离出的 GABA 突触小泡的冷冻电镜图像显示了完整的形态,呈圆形,并有突起的蛋白质密度。GABA突触小泡是有功能的,这是由一种混合(体外/体内)小泡融合试验评估的,它们在Ca2+触发下与合成的质膜模拟小泡同步融合,但作为阴性对照,它们在Mg2+触发下没有融合。我们的免疫分离方法也可用于其他类型的囊泡。
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引用次数: 0
Yeast supplementation potentiates fluoxetine's anti-depressant effect in mice via modulation of oxido-inflammatory, CREB, and MAPK signaling pathways 通过调节氧化-炎症、CREB 和 MAPK 信号通路,补充酵母可增强氟西汀对小鼠的抗抑郁作用
IF 2.1 Q3 PHYSIOLOGY Pub Date : 2024-01-01 DOI: 10.1016/j.crphys.2024.100132
Augustina Potokiri , Noah A. Omeiza , Abayomi M. Ajayi , Paul A. Adeleke , Abdullateef I. Alagbonsi , Ezekiel O. Iwalewa

Introduction

The therapeutic potential of yeast in the management of depression is unknown. Thus, we evaluated the modulatory effect of nutritional yeast supplementation on antidepressant activity of fluoxetine in mice models of depressive-like behaviors (DLB).

Methods

A total of 112 mice were divided into 16 groups (n = 7 each) for a 3-stage study. Stage I (non-DLB study) had groups Ia (10 mL/kg vehicle), Ib (20 mg/kg fluoxetine), Ic – If (2% yeast diet for all, but Id - If additionally received 5 mg/kg, 10 mg/kg, and 20 mg/kg fluoxetine respectively). Stage II (lipopolysaccharide [LPS] model of DLB) had groups IIa - IIb (10 mL/kg vehicle), IIc (20 mg/kg fluoxetine), IId (yeast) and IIe (yeast + 20 mg/kg fluoxetine). After these treatments for 24 days, animals in IIb - IIe received 0.83 mg/kg of LPS on the 25th day. Except for group IIIa (10 mL/kg vehicle), animals in other groups of stage III (unpredictable chronic mild stress [UCMS] model) were exposed to UCMS for 24 days along with 10 mL/kg vehicle (IIIb), 20 mg/kg fluoxetine (IIIc), yeast (IIId), or yeast + fluoxetine (IIIe).

Results

Yeast and fluoxetine attenuated LPS- and UCMS-induced immobility, derangement of oxido-inflammatory (TNF-α, IL-6, NO, MDA, SOD, GSH, CAT, and AChE) and CREB/MAPK pathways. While fluoxetine had more potent effect than yeast when used separately, pre-treatment of mice with their combination had more pronounced effect than either of them.

Conclusion

Yeast supplementation improves the antidepressant activity of fluoxetine in mice by modulating oxido-inflammatory, CREB, and MAPK pathways.
引言 酵母在治疗抑郁症方面的潜力尚不清楚。因此,我们评估了在抑郁样行为(DLB)小鼠模型中补充营养酵母对氟西汀抗抑郁活性的调节作用。第一阶段(非 DLB 研究)分为 Ia 组(10 毫升/千克载体)、Ib 组(20 毫克/千克氟西汀)、Ic - If 组(均为 2% 酵母饮食,但 Id - If 组分别额外摄入 5 毫克/千克、10 毫克/千克和 20 毫克/千克氟西汀)。第二阶段(脂多糖[LPS]DLB 模型)分为 IIa - IIb 组(10 毫升/千克载体)、IIc 组(20 毫克/千克氟西汀)、IId 组(酵母)和 IIe 组(酵母 + 20 毫克/千克氟西汀)。经过 24 天的治疗后,IIb - IIe 组动物在第 25 天接受了 0.83 毫克/千克的 LPS。除 IIIa 组(10 毫升/千克载体)外,第三阶段(不可预知的慢性温和应激 [UCMS] 模型)其他各组的动物均暴露于 UCMS 24 天,同时接受 10 毫升/千克载体(IIIb)、20 毫克/千克氟西汀(IIIc)、酵母(IIId)或酵母 + 氟西汀(IIIe)的治疗。结果酵母和氟西汀减轻了 LPS 和 UCMS 诱导的不运动、氧化-炎症(TNF-α、IL-6、NO、MDA、SOD、GSH、CAT 和 AChE)和 CREB/MAPK 通路的失调。结论补充酵母可通过调节氧化-炎症、CREB 和 MAPK 通路改善氟西汀在小鼠体内的抗抑郁活性。
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Current research in physiology
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