2005年2月
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
JOURNAL OF NEUROSCIENCE
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- 巻
- 25
- 号
- 5
- 開始ページ
- 1081
- 終了ページ
- 1088
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1523/JNEUROSCI.2565.04.2005
- 出版者・発行元
- SOC NEUROSCIENCE
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 (<10 weeks old) mutant mice show normal LTP and learning abilities in the Morris water maze task, whereas 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.
- リンク情報
- ID情報
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- DOI : 10.1523/JNEUROSCI.2565.04.2005
- ISSN : 0270-6474
- PubMed ID : 15689543
- Web of Science ID : WOS:000226750600005