Liquid Diet Induces Memory Impairment Accompanied by a Decreased Number of Hippocampal Neurons in Mice

Liquid Diet Induces Memory Impairment Accompanied by a Decreased Number of Hippocampal Neurons in Mice
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DOI:
10.1002/jnr.23383
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发表时间:
2014-08-01
影响因子:
4.2
通讯作者:
Michikawa, Makoto
Michikawa, Makoto
中科院分区:
医学3区
文献类型:
--
作者:
Okihara, Hidemasa;Ito, Jin-ichi;Michikawa, Makoto

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提示咀嚼功能障碍影响中枢神经系统;然而,其潜在机制尚不清楚。脑源性神经营养因子(BDNF)及其受体TrkB在记忆和学习中起着重要作用。在本研究中,我们检测了咀嚼对小鼠记忆、BDNF和TrkB表达水平以及海马神经元数量的影响。选取雄性C57 BL/6J小鼠(3周龄),随机分为对照组(N=7)和试验组(N=7),对照组(N=7)饲喂食物颗粒,试验组(N=7)饲喂减少进食时咀嚼的液体饲料。在14周龄时,我们进行了被动回避测试,发现实验组的记忆和学习能力与对照组相比有所下降。行为实验结束后,采集大脑并进行形态学和生化分析。实验组海马中BDNF表达水平显著高于对照组,TrkB表达水平低于对照组。在大脑皮层中,这些水平在两组之间保持不变。BDNF/TrkB信号下游分子phospho-p44/42 ERK/pan ERK在实验组皮层和海马区的比值显著低于对照组。实验组海马锥体神经元数量明显低于对照组。这些发现表明,儿童早期由流质饮食引起的咀嚼减少可能会损害记忆和学习能力,并伴有海马神经元的丧失。(C) 2014 Wiley期刊公司
It is suggested that masticatory dysfunction affects the central nervous system; however, the underlying mechanism remains unknown. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are known to play important roles in memory and learning. In this study, we examined the effects of mastication on memory, the expression levels of BDNF and TrkB, and the number of neurons in the hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into the control group (N=7) fed chow pellets and the experimental group (N=7) fed a liquid diet, which reduces mastication during eating. At 14 weeks of age, we performed a passive avoidance test and found that memory and learning ability were impaired in the experimental group compared with the control group. After the behavioral experiment, brains were harvested and analyzed morphologically and biochemically. In the hippocampus of the experimental group, the expression levels of BDNF were significantly higher, whereas those of TrkB were lower than those of the control group. In the cerebral cortex, these levels remained unchanged between the two groups. The ratio of phospho-p44/42 ERK/pan ERK, a downstream molecule of BDNF/TrkB signaling, in the experimental group was significantly lower than that of the control group in the cortex and hippocampus. The number of pyramidal neurons in the hippocampus was lower in the experimental group than in the control group. These findings suggest that reduced mastication induced by a liquid diet in early childhood may impair memory and learning ability, accompanied by neuronal loss in the hippocampus. (C) 2014 Wiley Periodicals, Inc.