在妊娠期和哺乳期喂食二甲双胍可改善发热惊厥大鼠后代的学习和记忆损伤:氧化应激和炎症反应的作用

IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Niloofar Khoshroo, Ali Rahimi, Samaneh Kakhki, Fatemeh Kaffashan, Maha Masoudi, Soheil Baharlou, Farimah Beheshti
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引用次数: 0

摘要

背景:许多临床证据表明,婴幼儿暴露于高热环境后发生惊厥的风险较高,更有可能造成脑损伤并影响认知功能,因此,许多研究集中于预防或治疗发热性惊厥(FS),并将其不良反应降至最低。考虑到氧化应激是诱发热性惊厥的重要因素,而二甲双胍具有抗氧化作用,本研究旨在探讨二甲双胍在产前和哺乳期对热性惊厥大鼠幼仔的保护作用:将妊娠大鼠分为6组:(1)载体组:妊娠大鼠在妊娠期和哺乳期接受生理盐水;(2)FS组:妊娠大鼠在妊娠期和哺乳期接受生理盐水;(3-5)FS-Met50/100/150 mg/kg组:妊娠大鼠在妊娠期和哺乳期接受不同剂量的二甲双胍,包括50、100和150 mg/kg;(6)Met150 mg/kg组:妊娠大鼠在妊娠期和哺乳期接受Met150 mg/kg。在所有 FS 组中,母鼠所生的雄性幼鼠都接受了热疗。所有实验组的大鼠都在哺乳期内长大,哺乳期结束后,对它们进行行为测试和生化分析:结果:本研究结果表明,产前和哺乳期暴露于最高剂量二甲双胍的小鼠在行为和生化测试分析中与FS组存在显著差异。虽然其余剂量的二甲双胍也有效,但最高剂量的二甲双胍(150 毫克/千克)的效果更好。有趣的是,在探针试验测试中,单独使用最高剂量的二甲双胍比使用药物的效果更好:考虑到目前有关二甲双胍改善癫痫症状的研究和相关研究,有大量证据表明二甲双胍对癫痫发作有积极影响。虽然确切的机制尚不清楚,但二甲双胍的抗氧化作用得到了强有力的支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Feeding metformin during pregnancy and lactation periods improved learning and memory impairment in the rat offspring exposed to febrile seizure: Role of oxidative stress and inflammatory response

Feeding metformin during pregnancy and lactation periods improved learning and memory impairment in the rat offspring exposed to febrile seizure: Role of oxidative stress and inflammatory response

Background

Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti-oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure.

Method and materials

Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3–5) FS-Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis.

Results

According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test.

Conclusion

Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti-oxidant effect of metformin is strongly supported.

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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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