Neuropharmacology最新文献_第6页

Pharmacological characterization of the novel selective kappa opioid receptor agonists 10-Iodo-Akuammicine and 10-Bromo-akuammicine in mice

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-23 DOI: 10.1016/j.neuropharm.2025.110316

Kathryn Bland , Chongguang Chen , Peng Huang , Conrad Ho , Theodora Howe , Katrina Ocampo , Pingwei Zhao , Simone Creed , Joseph Noel-Torres , Andrew P. Riley , Lee-Yuan Liu-Chen

Akuammicine (AKC), an indole alkaloid, is a kappa opioid receptor (KOR) full agonist with a moderate affinity. 10-Iodo-akuammicine (I-AKC) and 10-Bromo-akuammicine (Br-AKC) showed higher affinities for the KOR with K_i values of 2.4 and 5.1 nM, respectively, and high selectivity for the KOR over other opioid receptors. Both were KOR full agonists. As AKC and derivatives have distinctly different chemical structures from other KOR agonists, herein we investigated whether Br-AKC and I-AKC produced similar pharmacological effects as typical KOR agonists. Br-AKC and I-AKC inhibited compound 48/80-induced scratching in a dose-dependent manner, with ED₅₀ values of 3.0 and 1.3 mg/kg (s.c.), respectively, indicating anti-pruritic activities. Side effects of I-AKC and Br-AKC and their promotion of KOR phosphorylation and internalization were examined using doses in the effective anti-scratch dose range, at 1.9-3.8x ED₅₀ and 1.7-3.3x ED₅₀, respectively. At 5 mg/kg, Br-AKC and I-AKC produced profound conditioned place aversion (CPA). Br-AKC (10 mg/kg), but not I-AKC (5 mg/kg), reduced novelty-induced hyperlocomotion, and Br-AKC impaired rotarod performance more profoundly than I-AKC. Br-AKC, but not I-AKC, caused KOR phosphorylation at S369 in the mouse brain and KOR internalization in the ventral tegmental area. These results indicate that Br-AKC and I-AKC produce anti-scratch effect and CPA, similar to typical KOR agonists. However, there are some differences between the two. In addition, KOR phosphorylation and internalization in mouse brains are not associated with CPA but may be related to hypolocomotion and impaired rotarod performance. This is the first in vivo pharmacological characterization of AKC derivatives.

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引用次数: 0

Antisocial personality disorder:Failure to balance excitation/inhibition?

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-22 DOI: 10.1016/j.neuropharm.2025.110321

Klaus-Peter Lesch , Nikita Gorbunov

While healthy brain function relies on a dynamic but tightly regulated interaction between excitation (E) and inhibition (I), a spectrum of social cognition disorders, including antisocial behavior and antisocial personality disorder (ASPD), frequently ensuing from irregular neurodevelopment, may be associated with E/I imbalance and concomitant alterations in neural connectivity. Technological advances in the evaluation of structural and functional E/I balance proxies in clinical settings and in human cell culture models provide a general basis for identification of biomarkers providing a powerful concept for prevention and intervention across different dimensions of mental health and disease. In this perspective we outline a framework for research to characterize neurodevelopmental pathways to antisocial behavior and ASPD driven by (epi)genetic factors across life, and to identify molecular targets for preventing the detrimental effects of cognitive dysfunction and maladaptive social behavior, considering psychosocial experience; to validate signatures of E/I imbalance and altered myelination proxies as biomarkers of pathogenic neural circuitry mechanisms to determine etiological processes in the transition from mental health to antisocial behavior and ASPD and in the switch from prevention to treatment; to develop a neurobiologically-grounded integrative model of antisocial behavior and ASPD resultant of disrupted E/I balance, allowing to establish objective diagnoses and monitoring tools, to personalize prevention and therapeutic decisions, to predict treatment response, and thus counteract relapse; and finally, to promote transformation of dimensional disorder taxonomy and to enhance societal awareness and reception of the neurobiological basis of antisocial behavior and ASPD.

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引用次数: 0

In vivo calcium extrusion from accumbal astrocytes reduces anxiety-like behaviors but increases compulsive-like responses and compulsive ethanol drinking in mice

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-20 DOI: 10.1016/j.neuropharm.2025.110320

Lee Peyton , Humza Haroon , Anthony Umpierre , Hesham Essa , Robert Bruce , Long-Jun Wu , Doo-Sup Choi

The ventral striatum is crucially involved in reward processing. The present study investigates the behavioral effects of astrocyte-specific calcium extrusion virus “CalEx” on perseverative responses in the operant five-choice serial reaction time task and ethanol-conditioned place preference. Mice were injected with CalEx via the GfaABC₁D promoter to extrude cytosolic calcium from astrocytes within the ventral striatum. We found that CalEx transfection in the ventral striatum reduced evoked response duration, the maximum amplitude, and the response frequency to 500 μM ATP as measured by ΔF/F fluorescence intensity of the genetically encoded calcium indicator targeting astrocytes GCaMP6f. During the five-choice serial reaction time task, CalEx mice persisted in perseverative responses compared to their counterparts. Additionally, during ethanol-conditioned place preference, CalEx mice showed increased place preference for a low ethanol concentration compared to control group. Furthermore, we found that accumbal astrocytic calcium extrusion increased quinine adulterated ethanol drinking. Our findings suggest that diminishing ventral striatum astrocyte calcium activity contributes to compulsive behaviors, ethanol drinking, and enhanced ethanol drug reward.

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引用次数: 0

MK-801 attenuates one-trial tolerance in the elevated plus maze via the thalamic nucleus reuniens

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-20 DOI: 10.1016/j.neuropharm.2025.110318

Xue Xu , Qian Gong , Xiao-Dong Wang

Anxiety, a future-oriented negative emotional state, is characterized by heightened arousal and vigilance. The elevated plus maze (EPM) test is a widely used assay of anxiety-related behaviors in rodents and shows a phenomenon where animals with prior test experience tend to avoid open arms in retest sessions. While this one-trial tolerance (OTT) phenomenon limits the reuse of the EPM test, the potential mechanisms remain unsolved. Here, we found that neither anxiogenic factors like acute restraint stress nor anxiolytic factors like diazepam (2 mg/kg) influenced the emergence of the OTT phenomenon in mice in the EPM test. In contrast, OTT was markedly attenuated by MK-801 (0.1 mg/kg), a non-competitive N-methyl-D-aspartate receptor antagonist. Through the use of c-fos mapping, MK-801 was found to increase neuronal activation in the thalamic nucleus reuniens (Re). Moreover, chemogenetic inactivation of Re neurons could prevent the effects of MK-801. Our findings suggest the Re as a crucial brain region in emotional adaptation in the EPM and shed light on the experimental design optimization and mechanistic investigation of anxiety-related behaviors.

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引用次数: 0

The class-IIa HDAC inhibitor TMP269 promotes BMP-Smad signalling and is neuroprotective in in vitro and in vivo 6-hydroxydopamine models of Parkinson's disease

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-20 DOI: 10.1016/j.neuropharm.2025.110319

Adam G. O'Mahony , Martina Mazzocchi , Alex Morris , Noelia Morales-Prieto , Caitriona Guinane , Sean L. Wyatt , Louise M. Collins , Aideen M. Sullivan , Gerard W. O'Keeffe

Degeneration of midbrain nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). Peripheral delivery of a compound(s) to arrest or slow this dopaminergic degeneration is a key therapeutic goal. Pan-inhibitors of histone deacetylase (HDAC) enzymes, key epigenetic regulators, have shown therapeutic promise in PD models. However as there are several classes of HDACs (ClassI-IV), class-specific inhibition will be important to ensure target specificity. Here we examine the neuroprotective potential of the Class-IIa HDAC inhibitor, TMP269. We show that TMP269 protected against 6-hydroxydopamine (6-OHDA)-induced neurite injury in SH-SY5Y cells and cultured rat ventral mesencephalic dopaminergic neurons. We find that TMP269 upregulated the neurotrophic factor BMP2 and BMP-Smad dependent transcription signalling in SH-SY5Y cells, which was necessary for its neuroprotective effect against 6-OHDA-induced injury. Furthermore, peripheral continuous infusion of 0.5 mg/kg of TMP269 for 7 days via a mini-osmotic pump, reduced forelimb impairments induced by striatal 6-OHDA administration. TMP269 also protected dopaminergic neurons in the substantia nigra and their striatal terminals from striatal 6-OHDA-induced neurodegeneration and prevented the 6-OHDA-induced increases in the numbers of IBA1-positive microglia in the striatum and substantia nigra in vivo. TMP269 also prevented 6-OHDA-induced decreases in BMP2, pSmad1/5 and acetylated histone 3 levels, and it reversed 6-OHDA-induced increase in nuclear HDAC5 in dopaminergic neurons in the substantia nigra. These data add to the growing body of evidence that Class-IIa specific HDAC inhibitors may be pharmacological agents of interest for peripheral delivery with the goal of neuroprotection in PD.

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引用次数: 0

Exploring DMT: Endogenous role and therapeutic potential 探索DMT：内源性作用和治疗潜力。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-18 DOI: 10.1016/j.neuropharm.2025.110314

Jakub Schimmelpfennig, Kamila Jankowiak-Siuda

N,N-Dimethyltryptamine (DMT) is a naturally occurring amine and psychedelic compound, found in plants, animals, and humans. While initial studies reported only trace amounts of DMT in mammalian brains, recent findings have identified alternative methylation pathways and DMT levels comparable to classical neurotransmitters in rodent brains, calling for a re-evaluation of its biological role and exploration of this inconsistency. This study evaluated DMT's biosynthetic pathways, focusing on indolethylamine N-methyltransferase (INMT) and its isoforms, and possible regulatory mechanisms, including alternative routes of synthesis and how physiological conditions, such as stress and hypoxia influence DMT levels. This review considers the impact of endogenous regulatory factors on DMT synthesis and degradation, particularly under conditions affecting monoamine oxidase (MAO) efficiency and activity. We also examined DMT's potential roles in various physiological processes, including neuroplasticity and neurogenesis, mitochondrial homeostasis, immunomodulation, and protection against hypoxia and oxidative stress. DMT's lipophilic properties allow it to cross cell membranes and activate intracellular 5-HT2A receptors, contributing to its role in neuroplasticity. This suggests DMT may act as an endogenous ligand for intracellular receptors, highlighting its broader biological significance beyond traditional receptor pathways. The widespread evolutionary presence of DMT's biosynthetic pathways across diverse species suggests it may play essential roles in various developmental stages and cellular adaptation to environmental challenges, highlighting the neurobiological significance of DMT and its potential clinical applications. We propose further research to explore the role of endogenous DMT, particularly as a potential neurotransmitter.

N，N-二甲基色胺（DMT）是一种天然存在的胺和迷幻化合物，存在于植物、动物和人类中。虽然最初的研究仅报道了哺乳动物大脑中微量的DMT，但最近的发现已经确定了可替代的甲基化途径和DMT水平，与啮齿动物大脑中的经典神经递质相当，要求重新评估其生物学作用并探索这种不一致性。本研究评估了DMT的生物合成途径，重点关注吲哚乙胺n -甲基转移酶（INMT）及其异构体，以及可能的调控机制，包括合成的替代途径以及生理条件（如应激和缺氧）如何影响DMT水平。本文综述了内源性调控因子对DMT合成和降解的影响，特别是在影响单胺氧化酶（MAO）效率和活性的条件下。我们还研究了DMT在各种生理过程中的潜在作用，包括神经可塑性和神经发生、线粒体稳态、免疫调节以及对缺氧和氧化应激的保护。DMT的亲脂性使其能够穿过细胞膜并激活细胞内5-HT2A受体，有助于其在神经可塑性中的作用。这表明DMT可能作为细胞内受体的内源性配体，突出了其超越传统受体途径的更广泛的生物学意义。DMT生物合成途径在不同物种中的广泛进化表明，它可能在不同发育阶段和细胞对环境挑战的适应中发挥重要作用，突出了DMT的神经生物学意义及其潜在的临床应用。我们建议进一步研究内源性DMT的作用，特别是作为一种潜在的神经递质。

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引用次数: 0

Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice 一种新的小鼠口鼻限制尼古丁雾化自我给药模型的表征。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-18 DOI: 10.1016/j.neuropharm.2025.110315

Lois S. Akinola , Belle Buzzi , Erin Kalck, Kimmie Le, Sarah Klein, Julian Vaughn, Jamil Basir, Justin Poklis, Paul Whiteaker, Keith L. Shelton, M. Imad Damaj

Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine. Our studies show that male and female young adult mice respond to nicotine, demonstrating notable sex-related differences in intake, locomotor sensitization, and somatic withdrawal signs. In addition, we characterized intake in adolescent mice, showing sex differences as well. Finally, we showed genotype-related differences when using β2 knock-out mice, emphasizing the role of the β2 nAChR in nicotine reward and nicotine intake. This new model offers a more targeted approach to studying the potential risks of nicotine vaping in a more relevant and face-valid model compared to traditional whole-body nicotine vapor exposure in rodents.

在美国，尼古丁的使用仍然是导致可预防死亡的主要原因之一，虽然可燃香烟的使用在过去几年中有所下降，但电子尼古丁输送系统的普及程度仍在上升。电子烟并非没有风险，其长期影响，尤其是对弱势群体的影响，在很大程度上仍不得而知。本研究介绍了一种新颖的、口鼻受限的、尼古丁雾化自我给药小鼠模型，以研究尼古丁浓度、基因型、性别和年龄对尼古丁自我给药和行为反应的影响。我们的研究表明，雄性和雌性年轻成年小鼠对尼古丁有反应，在摄入量、运动敏化和躯体戒断症状方面表现出显著的性别差异。此外，我们描述了青春期小鼠的摄入量，也显示出性别差异。最后，我们在使用β2敲除小鼠时显示了基因型相关的差异，强调了β2 nAChR在尼古丁奖励和尼古丁摄入中的作用。与传统的啮齿动物全身尼古丁蒸汽暴露相比，这个新模型提供了一种更有针对性的方法，以一种更相关、更有效的模型来研究尼古丁蒸汽的潜在风险。

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引用次数: 0

Age- and cytokine-dependent modulation of GABAergic transmission within the basolateral amygdala of male Sprague Dawley rats 雄性大鼠基底外侧杏仁核内gaba能传递的年龄和细胞因子依赖性调节。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-17 DOI: 10.1016/j.neuropharm.2025.110304

Marvin R. Diaz, Thaddeus M. Barney, Paige Marsland, Terrence Deak

Alcohol binge drinking has a multitude of effects on CNS function, including changes in inflammatory cytokines such as IL-6 and IL-1β that may contribute to mood fluctuations associated with the intoxication-withdrawal cycle. Widely throughout the brain, including the amygdala, IL-6 mRNA is enhanced during intoxication, whereas IL-1β is initially suppressed during alcohol intoxication, with increased expression seen shortly after ethanol clearance, during acute hangover. Furthermore, induction of neuroimmune genes appears to be muted during adolescence in the amygdala, suggesting a broader functional immaturity of the adolescent neuroimmune system in structures involved in negative affect associated with ethanol exposure. However, neither the effect of IL-6 or IL-1β on synaptic function within the amygdala nor the impact of acute intoxication and withdrawal on these cytokines’ function are known. To test this, we used whole-cell patch-clamp electrophysiology to assess the effects of IL-6 and IL-1β on GABA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in BLA pyramidal neurons from male rats in early adolescence (P28-40) or adulthood (P70+). These experiments were done in naïve, intoxicated (3–4 h following an intraperitoneal injection of 3.5 g/kg ethanol), and during acute hangover (11–18 h post ethanol injection). In naïve males, we found that IL-6 (10 ng/ml) significantly enhanced sIPSC amplitude only in adults, with no apparent effect in adolescents; this effect of IL-6 in adults was not different during intoxication. Conversely, IL-1β (10 ng/ml) did not alter sIPSC frequency in any group (naïve or hangover adolescents or adults). Unlike our previous work in adult rats, here we found that contextual fear conditioning was not altered in adolescents when conditioned during acute hangover. Together, these observations suggest that IL-6, but not IL-1β, regulation of BLA GABA transmission emerges as a function of age, but is not affected by acute ethanol exposure or hangover for adolescents or adults. Importantly, these findings provide additional evidence to support functional immaturity of the neuroimmune system in adolescence.

酗酒对中枢神经系统功能有多种影响，包括炎症细胞因子如IL-6和IL-1β的变化，这可能导致与醉酒-戒断周期相关的情绪波动。在包括杏仁核在内的整个大脑中，IL-6 mRNA在醉酒期间增强，而IL-1β在酒精中毒期间最初被抑制，在急性宿醉期间酒精清除后不久表达增加。此外，在青春期杏仁核中，神经免疫基因的诱导似乎是沉默的，这表明青少年神经免疫系统在与酒精暴露相关的负面影响结构中存在更广泛的功能不成熟。然而，IL-6或IL-1β对杏仁核突触功能的影响以及急性中毒和戒断对这些细胞因子功能的影响都不清楚。为了验证这一点，我们使用全细胞膜片钳电生理学来评估IL-6和IL-1β对青春期早期（P28-40）或成年期（P70+）雄性大鼠BLA锥体神经元中gaba介导的自发抑制性突触后电流（sIPSCs）的影响。这些实验分别在naïve、醉酒（3-4小时后腹腔注射3.5 g/kg乙醇）和急性宿醉（11-18小时后注射乙醇）期间进行。在naïve男性中，我们发现IL-6 （10 ng/ml）仅在成人中显著增强sIPSC振幅，在青少年中无明显作用；IL-6在成人中毒期间的作用没有差异。相反，IL-1β (10 ng/ml)不会改变任何组（naïve或宿醉青少年或成年人）sIPSC的频率。与我们之前对成年大鼠的研究不同，我们发现在急性宿醉期间，青少年的情境恐惧条件反射并没有改变。总之，这些观察结果表明，IL-6，而不是IL-1β，对BLA - GABA传输的调节是作为年龄的函数出现的，但不受青少年或成人急性乙醇暴露或宿醉的影响。重要的是，这些发现为支持青少年神经免疫系统功能不成熟提供了额外的证据。

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引用次数: 0

Synaptic protein expression in bipolar disorder patient-derived neurons implicates PSD-95 as a marker of lithium response 双相情感障碍患者源性神经元突触蛋白表达暗示PSD-95是锂反应的标志物。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-15 DOI: 10.1016/j.neuropharm.2025.110313

Kayla E. Rohr , Himanshu K. Mishra , Johansen Amin , Timothy Nakhla , Michael J. McCarthy

Bipolar disorder (BD) is a severe mental illness characterized by recurrent episodes of depression and mania. Lithium is the gold standard pharmacotherapy for BD, but outcomes are variable, and the relevant therapeutic mechanisms underlying successful treatment response remain uncertain. To identify synaptic markers of BD and lithium response, we measured the effects of lithium on induced pluripotent stem cell-derived neurons from BD patients and controls. We determined that baseline expression of synapsin I (SYN1) and PSD-95 is reduced in BD neurons compared to controls. In control neurons, lithium treatment had modest, transient effects increasing SYN1 and PSD-95 expression. In BD neurons, lithium increased SYN1 expression regardless of lithium response history. However, lithium only increased PSD-95 expression selectively in neurons from lithium-responders and not in neurons from lithium non-responders, leading to group differences in the colocalization of SYN1 and PSD-95. In conclusion, this preliminary work indicates synaptic protein markers are associated with BD pathology and correction of post-synaptic protein expression may be an important mechanism underlying lithium response.

双相情感障碍（BD）是一种严重的精神疾病，其特征是反复发作的抑郁和躁狂。锂是双相障碍的金标准药物治疗，但结果是可变的，成功治疗反应的相关治疗机制仍然不确定。为了确定BD和锂反应的突触标志物，我们测量了锂对BD患者和对照组诱导多能干细胞来源的神经元的影响。我们确定，与对照组相比，BD神经元中突触素I （SYN1）和PSD-95的基线表达减少。在对照神经元中，锂处理对SYN1和PSD-95的表达有轻微的、短暂的影响。在BD神经元中，无论锂反应历史如何，锂都增加了SYN1的表达。然而，锂只选择性地增加了锂应答者神经元中PSD-95的表达，而非锂应答者神经元中PSD-95的表达，导致SYN1和PSD-95共定位的组间差异。总之，这项初步工作表明突触蛋白标记物与BD病理相关，突触后蛋白表达的纠正可能是锂反应的重要机制。

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引用次数: 0

Swietenolide inhibits the TXNIP/NLRP3 pathways via Nrf2 activation to ameliorate cognitive dysfunction in diabetic mice 甜苷内酯通过激活Nrf2抑制TXNIP/NLRP3通路改善糖尿病小鼠认知功能障碍

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology

Pub Date : 2025-01-15 DOI: 10.1016/j.neuropharm.2025.110312

Xinquan Song , Siwen Fan , Yuetong Gao, Anxin Ma, Xiashu Zhang, Zihui Zhou, Yijia Zheng, Lei Du, Xia Zhu

Oxidative stress and inflammation play important roles in diabetic-associated cognitive dysfunction (DACD). Swietenolide (Std), isolated from the fruit of Swietenia macrophylla King, exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of Std on DACD remains unexplored. We utilized diabetic db/db mice and the hippocampal cell line HT22 to evaluate the effects and underlying molecular mechanisms of Std on DACD. Molecular docking study, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay analyses were conducted to elucidate the molecular mechanisms involved. We found that Std significantly improved cognitive dysfunction in diabetic mice and increased cell viability in HT22 cells under high glucose condition. The reduction in superoxide dismutase (SOD) enzamy activity and glutathione (GSH) level, along with an increase in malondialdehyde (MDA) induced by high glucose in hippocampus, were reversed by Std treatment. Furthermore, Std effectively diminished the levels of proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Importantly, Std markedly activated the Nrf2 pathway to inhibit the thioredoxin-interacting protein/NOD-like receptor protein 3 (TXNIP/NLRP3) pathways. However, the neuroprotective effect of Std was significantly weakened by Nrf2 inhibitor ML385. These results indicate that Std provides substantial protection against high glucose-induced hippocampal injury by inhibiting the TXNIP/NLRP3 pathways dependent on Nrf2, which may serve as a promising agent for attenuating DACD.

氧化应激和炎症在糖尿病相关认知功能障碍（daca）中起重要作用。甜苷内酯（Std）是从大叶甜苷（sweetenia macrophylla King）的果实中分离出来的，具有抗氧化、抗炎、抗肿瘤等多种有效的药理活性。然而，性病对ddad的影响仍未被探索。我们利用糖尿病db/db小鼠和海马细胞系HT22来研究Std对ddad的影响及其可能的分子机制。通过分子对接研究、免疫印迹、免疫组织化学和酶联免疫吸附分析来阐明所涉及的分子机制。我们发现，在高糖条件下，Std显著改善糖尿病小鼠的认知功能障碍，提高HT22细胞的活力。高糖诱导的海马超氧化物歧化酶（SOD）酶活性和谷胱甘肽（GSH）水平的降低，以及丙二醛（MDA）水平的升高，被Std处理逆转。此外，Std有效降低了促炎细胞因子白介素-1β (IL-1β)和肿瘤坏死因子-α (TNF-α)的水平。重要的是，Std显著激活Nrf2通路，抑制硫氧还蛋白相互作用蛋白/ nod样受体蛋白3 （TXNIP/NLRP3）通路。然而，Nrf2抑制剂ML385显著削弱了Std的神经保护作用。这些结果表明，Std通过抑制依赖于Nrf2的TXNIP/NLRP3通路，对高糖诱导的海马损伤提供了实质性的保护，这可能是一种有希望的减轻ddad的药物。

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引用次数: 0