Effects of metformin on behavioral alterations produced by chronic sucrose consumption in male rats

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Mariana Rey, Héctor Coirini, Agustina Marchena, María Claudia González Deniselle, María Sol Kruse
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引用次数: 0

Abstract

Excessive consumption of sugary drinks negatively impacts the developing brain, producing long-lasting behavioral and metabolic disorders. Here, we study whether treatment with the antihyperglycemic agent metformin prevents some of the anxiety and memory alterations produced by chronic sucrose consumption. Male Sprague–Dawley rats had unrestricted access to water (control group) and a bottle containing a 10% sucrose solution (sucrose group, SUC) for 35 days. In parallel, a group of animals from SUC received metformin (25 mg/kg or 50 mg/kg, orally; MET 25 and MET 50 groups, respectively). After 2 weeks of metformin treatment, the animals weighed less than controls. SUC and MET 50 groups compensated for the caloric intake from the sugary solution by consuming less chow. In contrast, total energy intake in MET 25 was higher than the rest of the groups, but they still weighed less than control and SUC groups, suggesting that at this concentration, metformin delays body growth. The animals were then tested for the open field (OF), elevated plus maze (EPM) and novel object location (NOL) tests. In the OF, SUC animals spent more time in the central zone of the arena, evidenced by an increased number of entries and the distance traveled there. In the EPM, SUC animals spent more time in the open arms and less time in the central square. Metformin treatment prevented the decreased anxiety observed in SUC animals in the OF and EPM. In the NOL test, SUC animals showed less interest in novelty and metformin treatment did not improve this alteration. The preference for open spaces in the OF and EPM were associated with increased serum triglycerides (TG) and malondialdehyde levels in the medial prefrontal cortex (mPFC) and the hippocampus (HIP), while poor memory performance was associated with high basal blood glucose levels. In conclusion, the decreased anxiety-like behavior produced by chronic sucrose consumption was prevented by metformin treatment, through a mechanism that probably involves normalization of TG levels and decreased oxidative stress in mPFC and HIP.

Abstract Image

二甲双胍对雄性大鼠长期摄入蔗糖导致的行为改变的影响
过量饮用含糖饮料会对发育中的大脑产生负面影响,造成长期的行为和代谢紊乱。在此,我们研究了二甲双胍是否能防止长期饮用蔗糖饮料导致的焦虑和记忆改变。雄性 Sprague-Dawley 大鼠可以不受限制地饮水(对照组)和饮用装有 10%蔗糖溶液的瓶子(蔗糖组,SUC)35 天。与此同时,SUC 组的一组动物接受二甲双胍治疗(25 毫克/千克或 50 毫克/千克,口服;分别为 MET 25 组和 MET 50 组)。二甲双胍治疗 2 周后,动物体重低于对照组。SUC 组和 MET 50 组通过减少饲料摄入来补偿从含糖溶液中摄入的热量。相比之下,MET 25 组的总能量摄入高于其他组,但它们的体重仍低于对照组和 SUC 组,这表明在此浓度下,二甲双胍会延缓身体生长。然后对动物进行开阔地(OF)、高架加迷宫(EPM)和新物体定位(NOL)测试。在开阔地迷宫中,SUC 动物在迷宫中央区域花费的时间更长,这体现在进入迷宫的次数和行进距离都有所增加。在EPM中,SUC动物在开放臂中花费的时间更多,而在中央广场花费的时间较少。二甲双胍治疗可防止在 OF 和 EPM 中观察到的 SUC 动物焦虑减少。在NOL测试中,SUC动物对新奇事物的兴趣较低,二甲双胍治疗并未改善这种变化。OF和EPM中对开放空间的偏好与内侧前额叶皮层(mPFC)和海马(HIP)血清甘油三酯(TG)和丙二醛水平的升高有关,而记忆表现不佳与基础血糖水平过高有关。总之,二甲双胍治疗可防止因长期摄入蔗糖而产生的焦虑样行为,其机制可能包括使内侧前额叶皮层和海马体的 TG 水平正常化和氧化应激减少。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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