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正常饮食与高脂肪饮食的对比研究:青春期雄性小鼠的行为和神经免疫变化。

Normal diet Vs High fat diet - A comparative study: Behavioral and neuroimmunological changes in adolescent male mice.

机构信息

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.

出版信息

Metab Brain Dis. 2018 Feb;33(1):177-190. doi: 10.1007/s11011-017-0140-z. Epub 2017 Nov 3.

Abstract

Recent evidence has established that consumption of High-fat diet (HFD)-induced obesity is associated with deficits in hippocampus-dependent memory/learning and mood states. Nevertheless the link between obesity and emotional disorders still remains to be elucidated. This issue is of particular interest during adolescence, which is important period for shaping learning/memory and mood regulation that can be sensitive to the detrimental effects of HFD. Our present study is focused to investigate behavioral and metabolic influences of short-term HFD intake in adolescent C57BL/6 mice. HFD caused weight gain, impaired glucose tolerance (IGT) and depression-like behavior as early as after 3 weeks which was clearly proved by a decrease in number of groomings in the open field test (OFT) and an increase in immobility time in the tail suspension test (TST). In the 4th week HFD induced obese model was fully developed and above behavioral symptoms were more dominant (decrease in number of crossings and groomings and increase in immobility time in both FST and TST). At the end of 6th week hippocampal analysis revealed the differences in morphology (reduced Nissl positive neurons and decreased the 5-HT receptor expression), neuronal survival (increased cleaved caspase-3 expression), synaptic plasticity (down regulation of p-CREB and BDNF), and inflammatory responses (increase in expression of pro-inflammatory cytokines and decrease in expression of anti-inflammatory cyokines) in HFD mice. Our results demonstrate that, high-fat feeding of adolescent mice could provoke "depression-like" behavior as early as 3 weeks and modulate structure, neuron survival and neuroinflammation in hippocampus as early as 6 weeks proving that adolescent age is much prone to adverse effects of HFD, which causes obesity, behavioral differences, memory and learning deficiencies.

摘要

最近的证据表明,高脂肪饮食(HFD)诱导的肥胖与海马依赖性记忆/学习和情绪状态缺陷有关。然而,肥胖和情绪障碍之间的联系仍有待阐明。在青春期,这个时期对学习/记忆和情绪调节的形成至关重要,而 HFD 的有害影响可能会对其产生影响,因此这是一个特别有趣的问题。我们目前的研究集中在研究短期 HFD 摄入对青春期 C57BL/6 小鼠的行为和代谢影响。HFD 导致体重增加、葡萄糖耐量受损(IGT)和抑郁样行为,早在 3 周后就明显表现出来,这一点可以通过在开阔场测试(OFT)中梳理次数减少和悬尾测试(TST)中不动时间增加来证明。在第 4 周,HFD 诱导的肥胖模型完全形成,上述行为症状更为明显(穿越和梳理次数减少,以及 FST 和 TST 中的不动时间增加)。在第 6 周结束时,海马分析显示形态学差异(减少 Nissl 阳性神经元和降低 5-HT 受体表达)、神经元存活(增加裂解的 caspase-3 表达)、突触可塑性(p-CREB 和 BDNF 下调)和炎症反应(促炎细胞因子表达增加和抗炎细胞因子表达减少)在 HFD 小鼠中。我们的结果表明,青春期小鼠高脂肪喂养早在 3 周就会引起“抑郁样”行为,并在 6 周内调节海马体的结构、神经元存活和神经炎症,证明青春期更容易受到 HFD 的不良影响,导致肥胖、行为差异、记忆和学习缺陷。

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