The role of Cyclophilin D in learning and memory
The role of Cyclophilin D in learning and memory
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DOI：
10.1002/hipo.20625
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发表时间：
2009-05
期刊：
影响因子：
3.5
通讯作者：
A. Mouri;Y. Noda;S. Shimizu;Y. Tsujimoto;T. Nabeshima
中科院分区：
文献类型：
--
作者：
A. Mouri;Y. Noda;S. Shimizu;Y. Tsujimoto;T. Nabeshima
亲环蛋白D （Cyp D）参与细胞死亡途径，阻断Cyp D可能是治疗退行性疾病（如阿尔茨海默病、缺血和多发性硬化症）的有效策略，但Cyp D的生理作用尚不明确。在这里，我们研究了缺乏Cyp D （Cyp D - / -）的小鼠在几种行为任务中的学习和记忆能力，以及Cyp D - / -小鼠学习和记忆能力与海马结构或神经元传递之间的关系。Cyp D - / -小鼠在Y迷宫中表现出短期记忆障碍，在新物体识别测试中表现出物体识别记忆障碍，在水迷宫测试中表现出参考记忆障碍，在条件恐惧学习测试中表现出联想学习障碍。海马输注与Cyp D结合的环孢素A，复制了在Cyp D - / -小鼠中观察到的海马依赖性认知缺陷。Nissl染色和GFAP免疫染色未显示Cyp D - / -小鼠的组织病理学异常，Western blotting未显示神经元和胶质标记蛋白的不规则表达。然而，与野生型小鼠相比，高钾处理后，Cyp D - / -小鼠海马中谷氨酸和乙酰胆碱的释放减少。这些结果表明Cyp D通过调节神经传递在学习和记忆中的生理作用。©2009 Wiley‐Liss, Inc。
Cyclophilin D (Cyp D) is implicated in cell death pathway and blockade of Cyp D could be a potent therapeutic strategy for degenerative disorders such as Alzheimer's disease, ischemia, and multiple sclerosis, but physiological role of Cyp D remains elusive. Here, we investigated the ability of learning and memory in several behavioral tasks in mice that lacked Cyp D (Cyp D−/−) and the relationship between ability of learning and memory and hippocampal architecture or neuronal transmission in Cyp D−/− mice. Cyp D−/− mice showed impairments of short‐term memory in the Y‐maze, object recognition memory in the novel‐object recognition test, reference memory in the water maze test, and associative learning in the conditioned fear learning test. Hippocampal infusion of Cyclosporine A, which binds to Cyp D, replicated the defect in hippocampus‐dependent cognition observed in Cyp D−/− mice. The Cyp D−/− mice did not show histopathological abnormalities upon Nissl staining and GFAP immunostaining or irregular expression of neuronal and glial marker proteins on Western blotting. However, release of glutamate and acetylcholine was decreased from the hippocampus in response to high‐potassium treatment in the Cyp D−/− mice than in the wild‐type mice. These results suggest a physiological role for Cyp D in learning and memory via the regulation of neurotransmission. © 2009 Wiley‐Liss, Inc.