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Publication : 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.

First Author  Niisato K Year  2005
Journal  J Neurosci Volume  25
Issue  5 Pages  1081-8
PubMed ID  15689543 Mgi Jnum  J:98253
Mgi Id  MGI:3577699 Doi  10.1523/JNEUROSCI.2565.04.2005
Citation  Niisato K, et al. (2005) 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. J Neurosci 25(5):1081-8
abstractText  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.
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