钠-葡萄糖共转运蛋白2抑制剂达格列净在创伤后应激障碍小鼠模型中逆转抑郁样行为

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-06-01 DOI:10.1016/j.brainresbull.2025.111414

Haneen Amawi , Tayma Makhlouf , Alaa M. Hammad , Sahar Alsheyab , Rawan Alhazaimeh , F. Scott Hall , Joyeeta T. Khan , Bahaa Al-Trad , Amit K. Tiwari

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引用次数: 0

摘要

创伤后应激障碍（PTSD）是一种心理状况，其特征是由于经历强烈的创伤事件（如战争或自然灾害）而导致持续的心理困扰。苯二氮卓类药物和选择性血清素再摄取抑制剂（SSRIs）被广泛用于治疗创伤后应激障碍，但它们的不良副作用令人担忧，而且它们作为创伤后应激障碍的对症治疗效果有限。此外，它们对创伤后应激障碍的核心潜在原因没有影响，研究报道了钠-葡萄糖共转运蛋白-2抑制剂（SGLTi）的潜在神经保护作用。本研究利用单次延长应激（SPS）小鼠创伤后应激障碍模型，包括连续暴露于不同应激源（2 小时约束，20 分钟强迫游泳，15 分钟休息，1-2 分钟乙醚暴露），研究新型SGLTi达格列净（Dapagliflozin， DAPA）在减轻SPS诱导的抑郁样行为方面的治疗潜力。方法将小白鼠随机分为4个实验组：对照组、SPS组、DAPA组(达格列净；1 mg/kg/天，灌胃7 d)， SPS+DAPA组。采用强迫游泳测验和悬尾测验对抑郁样行为进行行为评估。采集血液和脑组织样本分析应激标志物。结果sp组小鼠在给药后第7天表现出明显的抑郁样行为，经DAPA（1 mg/kg/d）治疗后逆转。在SPS组中，脑组织中Crh、Bax、Il1b和Bdnf的mRNA表达以及血清皮质酮的表达显著增加，而DAPA逆转了这些影响。结论DAPA（1 mg/kg）对ptsd诱发的抑郁样症状有潜在的治疗作用。

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Sodium-glucose cotransporter-2 inhibitor, dapagliflozin, reverses depressive-like behavior in a mouse model of post-traumatic stress disorder

Background

Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent psychological distress resulting from the experience of intense traumatic events, such as warfare or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are widely prescribed treatments for PTSD, but their adverse side effects are a significant concern and they have only limited efficacy as a symptomatic treatment for PTSD. Moreover, they have no effect on the core underlying causes of PTSD Studies have reported a potential neuroprotective effect for Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized the single-prolonged stress (SPS) mouse model of PTSD, which involved sequential exposure to different stressors (2 hours of restraint, 20 minutes of forced swimming, 15 minutes of rest, and 1–2 minutes of diethyl ether exposure), to investigate the therapeutic potential of Dapagliflozin (DAPA), a novel SGLTi, in mitigating the SPS-induced depressive-like behavior.

Methods

Male mice were randomly assigned to four experimental groups: Control group, SPS group, DAPA group (dapagliflozin; 1 mg/kg/day by oral gavage for 7 days), and SPS+DAPA group. Behavioral assessments for depressive-like behaviors were evaluated using the forced swim test and the tail suspension test. Blood and brain tissue samples were collected for analysis stress markers.

Results

SPS-treated mice showed significant depressive-like behavior on the seventh day post-treatment, which was reversed by DAPA treatment (1 mg/kg/day). Significant increases in brain tissue mRNA expression of Crh, Bax, Il1b, and Bdnf, as well as serum corticosterone, were observed in the SPS group, while DAPA reversed these effects.

Conclusion

This data indicates that DAPA (1 mg/kg) has potential therapeutic effects for the treatment of PTSD-induced depressive-like symptoms.

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.