Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice
Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice
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DOI：
10.3760/cma.j.issn.0366-6999.2011.10.019
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发表时间：
2011-05-20
影响因子：
6.1
通讯作者：
Zhang Jian-jun
中科院分区：
文献类型：
--
作者：
Jiang Qing-song;Liang Zi-liang;Zhang Jian-jun
背景无磨牙状态已被报道会损害学习和记忆功能。然而，目前还不清楚无磨牙的情况如何直接影响中枢神经系统，对大脑皮层和海马体的功能影响也没有详细描述。本研究旨在探讨快速老化小鼠（SAMP 8）双侧磨牙缺失后学习记忆障碍的分子机制，为临床预防老年性痴呆提供实验依据。每天监测动物的体重。分别于术后1、2、3个月进行水迷宫实验，测定大鼠的学习记忆能力。一旦检测到无磨牙组的逃避潜伏期显著延长，就在旷场试验中检查自发活动。随后，将动物斩首，解剖皮质和海马，进行蛋白质印迹法检测脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）及其高亲和力受体原肌球蛋白相关激酶B（tropomyosin related kinase B，TrkB）的表达水平。结果无磨牙组体重始终略低，但两组体重差异无统计学意义（P > 0.05）。与假手术组相比，去磨牙组在术后3个月的水迷宫实验中表现出较长的逃避潜伏期，而自主活动没有观察到差异。同时，在皮质和海马中，BDNF水平在无磨牙组中显著降低（P < 0.05），但无显著性差异;结论拔牙3个月后，SAMP 8小鼠的学习记忆能力受到影响，并且这种效应伴随着皮质和海马中BDNF表达的显著降低。中华医学杂志2011;124（10）：1540-1544
Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P > 0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P < 0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8 mice three months after teeth extraction, and this effect was accompanied by significantly reduced BDNF expression in the cortex and hippocampus. Chin Med J 2011;124(10):1540-1544