Age-Dependent Enhancement of Hippocampal Long-Term Potentiation and Impairment of Spatial Learning through the Rho-Associated Kinase Pathway in Protein Tyrosine Phosphatase Receptor Type Z-Deficient Mice
Age-Dependent Enhancement of Hippocampal Long-Term Potentiation and Impairment of Spatial Learning through the Rho-Associated Kinase Pathway in Protein Tyrosine Phosphatase Receptor Type Z-Deficient Mice
复制标题
DOI：
10.1523/jneurosci.2565.04.2005
复制
发表时间：
2005-02
期刊：
影响因子：
--
通讯作者：
K. Niisato;A. Fujikawa;S. Komai;T. Shintani;E. Watanabe;G. Sakaguchi;G. Katsuura;T. Manabe;M. Noda
中科院分区：
文献类型：
--
作者：
K. Niisato;A. Fujikawa;S. Komai;T. Shintani;E. Watanabe;G. Sakaguchi;G. Katsuura;T. Manabe;M. Noda
虽然蛋白酪氨酸磷酸酶（PTPs）在大脑中大量表达，但其在突触可塑性中的作用尚未得到很好的阐明。在这项研究中，我们研究了Ptprz的生理功能，这是一种受体型PTP主要在大脑中表达的硫酸软骨素蛋白聚糖。我们已经研究了表型突变小鼠缺乏Ptprz使用电生理，药理学和行为的方法。突变小鼠表现出增强的长时程增强（LTP）在海马脑片的CA1区和受损的空间学习能力在年龄依赖性的方式：年轻的成年人（13周龄）突变小鼠表现出增强的LTP和损害的任务。增强的LTP被Rho相关激酶（ROCK）的药理学抑制特异性抵消，ROCK是Rho的主要下游效应子。这些结果表明，Ptprz的缺乏导致ROCK的异常激活，从而导致切片中LTP的增强和动物的学习障碍。
Although protein tyrosine phosphatases (PTPs) are expressed abundantly in the brain, their roles in synaptic plasticity have not been well elucidated. In this study, we have examined the physiological functions of Ptprz, which is a receptor-type PTP expressed predominantly in the brain as a chondroitin sulfate proteoglycan. We have examined phenotypes of mutant mice deficient in Ptprz using electrophysiological, pharmacological, and behavioral approaches. Mutant mice exhibit enhanced long-term potentiation (LTP) in the CA1 region of hippocampal slices and impaired spatial learning abilities in an age-dependent manner: young adult (13 weeks old) mutant mice exhibit enhanced LTP and impairment in the task. The enhanced LTP is specifically canceled out by pharmacological inhibition of Rho-associated kinase (ROCK), a major downstream effector of Rho. These findings suggest that the lack of Ptprz leads to aberrant activation of ROCK and resultantly to enhanced LTP in the slice and learning impairments in the animal.