细胞周期蛋白依赖性激酶5/周期蛋白p35作为空间学习和记忆的关键调节因子发挥作用。

Cdk5/p35 functions as a crucial regulator of spatial learning and memory.

作者信息

Mishiba Tomohide, Tanaka Mika, Mita Naoki, He Xiaojuan, Sasamoto Kodai, Itohara Shigeyoshi, Ohshima Toshio

机构信息

Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan.

Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Saitama, 351-0198, Japan.

出版信息

Mol Brain. 2014 Nov 18;7:82. doi: 10.1186/s13041-014-0082-x.

BACKGROUND

Cyclin-dependent kinase 5 (Cdk5), which is activated by binding to p35 or p39, is involved in synaptic plasticity and affects learning and memory formation. In Cdk5 knockout (KO) mice and p35 KO mice, brain development is severely impaired because neuronal migration is impaired and lamination is disrupted. To avoid these developmental confounders, we generated inducible CreER-p35 conditional (cKO) mice to study the role of Cdk5/p35 in higher brain function.

RESULTS

CreER-p35 cKO mice exhibited spatial learning and memory impairments and reduced anxiety-like behavior. These phenotypes resulted from a decrease in the dendritic spine density of CA1 pyramidal neurons and defective long-term depression induction in the hippocampus.

CONCLUSIONS

Taken together, our findings reveal that Cdk5/p35 regulates spatial learning and memory, implicating Cdk5/p35 as a therapeutic target in neurological disorders.

背景

细胞周期蛋白依赖性激酶5（Cdk5）通过与p35或p39结合而被激活，参与突触可塑性并影响学习和记忆形成。在Cdk5基因敲除（KO）小鼠和p35基因敲除小鼠中，由于神经元迁移受损和分层紊乱，大脑发育严重受损。为避免这些发育混杂因素，我们构建了诱导型CreER-p35条件性（cKO）小鼠，以研究Cdk5/p35在高级脑功能中的作用。