Yukawa Kazunori, Tanaka Tetsuji, Bai Tao, Li Li, Tsubota Yuji, Owada-Makabe Kyoko, Maeda Masanobu, Hoshino Katsuaki, Akira Shizuo, Iso Hiroyuki
Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan.
Int J Mol Med. 2006 May;17(5):869-73.
Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent serine/threonine kinase that is thought to mediate apoptosis. DAPK is highly expressed in hippocampal neurons which are essential elements for memory formation. To examine if DAPK is implicated in spatial learning and memory, both wild-type and DAPK-mutant mice were subjected to Morris water maze tests. DAPK-mutant mice were generated by deleting 74 amino acids from the catalytic kinase domain of DAPK, and were used to investigate roles of the DAPK kinase domain in regulating spatial memory. Both mutant and wild-type mice were able to learn the water maze tasks to locate a hidden escape platform. In the first probe test, mutant mice showed a more precise memory for platform position compared to wild-type mice. In the reversal training in which the platform was located opposite from the original position, DAPK-mutant mice exhibited superior spatial learning compared to wild-type mice. DAPK-mutant mice also showed a more precise memory than their wild-type littermates in the probe trial of reversal test. Thus, the present results revealed crucial implications of DAPK in regulating spatial memory in mice.
死亡相关蛋白激酶（DAPK）是一种钙/钙调蛋白依赖性丝氨酸/苏氨酸激酶，被认为可介导细胞凋亡。DAPK在海马神经元中高度表达，而海马神经元是记忆形成的关键要素。为了研究DAPK是否与空间学习和记忆有关，对野生型和DAPK突变型小鼠都进行了莫里斯水迷宫试验。DAPK突变型小鼠是通过从DAPK的催化激酶结构域中删除74个氨基酸而产生的，用于研究DAPK激酶结构域在调节空间记忆中的作用。突变型和野生型小鼠都能够学会水迷宫任务以找到隐藏的逃生平台。在第一次探针试验中，与野生型小鼠相比，突变型小鼠对平台位置表现出更精确的记忆。在平台位于与原始位置相反方向的反转训练中，与野生型小鼠相比，DAPK突变型小鼠表现出更好的空间学习能力。在反转试验的探针试验中，DAPK突变型小鼠也比其野生型同窝小鼠表现出更精确的记忆。因此，目前的结果揭示了DAPK在调节小鼠空间记忆中的关键作用。
