Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice.
Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice.
复制标题
空间训练通过增强 Tg2576 小鼠的树突分支和脊柱生成来保留联想记忆能力
DOI：
10.1038/srep09488
复制
发表时间：
2015-03-30
影响因子：
4.6
通讯作者：
Liu GP
中科院分区：
文献类型：
--
作者：
Jiang X;Chai GS;Wang ZH;Hu Y;Li XG;Ma ZW;Wang Q;Wang JZ;Liu GP
阿尔茨海默病（AD）是最常见的神经退行性疾病，目前尚无有效的治疗方法。认知刺激可以延缓衰老和轻度认知障碍患者的记忆丧失。在3 × Tg-AD小鼠中，训练减少了神经病变，并短暂改善了记忆衰退。然而，学习改善记忆能力的神经生物学机制尚不清楚。本研究发现，Tg2576小鼠在Morris水迷宫（MWM）中的空间训练显著改善了情境恐惧条件反射检测的后续联想记忆获得。我们还发现，在训练后24小时，空间训练增强了海马齿状回（DG）和CA1神经元的长时程增强、树突分支和脊柱生成。在分子水平上，MWM训练显著激活了钙/钙调素依赖性蛋白激酶II (CaMKII)，升高了海马中谷氨酸AMPA受体GluA1亚基（GluA1）、突触后密度蛋白93 （PSD93）和突触后密度蛋白95 （PSD95）。最后，训练也显著改善ad样tau和淀粉样病变。我们得出结论，MWM的空间训练保留了Tg2576小鼠的联想记忆能力，其机制涉及海马树突分枝和脊柱生成的增加。
Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.
登录
查看更多内容
影响因子：
120.7
作者：
Ball, K;Berch, DB;Willis, SL
通讯作者：
Willis, SL
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T
影响因子：
56.9
作者：
Matsuo, Naoki;Reijmers, Leon;Mayford, Mark
通讯作者：
Mayford, Mark
影响因子：
2.5
作者：
Dong, Hongxin;Martin, Maureen V.;Csernansky, John G.
通讯作者：
Csernansky, John G.
影响因子：
16.2
作者：
McAllister, AK;Katz, LC;Lo, DC
通讯作者：
Lo, DC